Part of the life of Ms. Hanako Kadowaki.
\r\n\tThis book chapter’s main theme will be focused on transmission dynamics, pathogenesis, mechanisms of host interaction and response, epigenetics and markers, molecular diagnosis, RNA interacting proteins, RNA binding proteins, advanced development of tools for diagnosis, possible development of concepts for vaccines and anti drugs for RNA viruses, immunological mechanisms, treatment, prevention and control.
\r\n\t
For many years, Hansen’s disease patients’ rights were violated, and the four bioethical principles were ignored during the course of their treatment. In Table 1, we show part of the life of Ms. Hanako Kadowaki, who is 84 years old, blind, and a Hansen’s disease survivor [1].
\nListener: What do you think about the Leprosy Prevention Law? | \n
Mrs. Kadowaki: Because I was child, I did not understand it in detail, but enforced isolation means being treated like a criminal. Although my situation was not severe, the policeman and prefecture administrator came to our village many times. My friend’s father was forced into truck to be sent to the leprosarium while he was working. He was carpenter, and he asked the policeman, “Please wait until I have finished building this house.” They did not wait and forced him into the truck. This is what enforced isolation is like. I cried when I heard it. | \n
When I entered this leprosarium, it was filled with pilgrims who had been captured. At that time, the emphasis was on catching pilgrims, so this facility overflowed with residents. Pilgrims were gathered at the pier on the mainland. Pilgrims without handicaps were sent to another island, and pilgrims with handicaps were sent to this island. Thus, there were many handicapped pilgrims in this leprosarium at that time. | \n
Because they could not live in their hometowns, pilgrims were working and traveling around on both hot and cold days, and sleeping in front of shrines and temples and begging. They traveled with difficulty, and although they had no medical treatment, they were forced to work, so they became crippled by degrees. After decades of pilgrimage, they entered blind and with missing limbs, and I pitied them. There were lice, there were fleas, and there were bedbugs. It was very terrible, and the pilgrims had nothing except their own bodies, but my isolation was not completely terrible. | \n
At that time, dying patients could not be cared for by the nurse, so they died in a terrible situation. They died weak, without food, saying, “I want to die after drinking myself full of wine,” or “I want to eat sweets.” I felt pity for those dying people at the time. Their funeral was shabby, too. | \n
The meals were skimpy. When the war was intense, there was no food, no clothing, no soap, and no medical treatment. After the war, there was still little food, and I was hungry, so I asked an outside person to buy food for me, as I was ashamed to ask anyone inside. | \n
At that time, the roads were bad, and there was not a bell and white line on the road to support and lead blind people. Blind people had white canes made by a kind man who took branches from the mountain and shaved them down. The blind people worked at exploring with their white canes and walked from one end of the island to another in order to get treatment. They had many difficulties. | \n
There were patients with no fingers. If they had fingers, they were dangling from paralysis or they did not have all five. Now I regret that I did not support them more at the time. Because now my fingers are short, and I am an inconvenience, just like how those patients with no fingers were inconvenient. At that time, because I could still sew with a needle, I was not inconvenienced. I could not understand their inconvenience. And at that time, when we had wounds from washing our clothes or dishes, the doctor cut down the finger immediately, like cutting a radish. A foot was changed out for a prosthetic leg immediately. It was not serious. | \n
Temporarily coming back home from the leprosarium was real difficult at that time. We had to write many difficult things in our petition and submit it and get permission from the chief at the leprosarium. Permission was only for 1 week, so after going home, we submitted another petition and asked to extend it to 2 weeks. We used the local train and it took time, so we could only stay about 10 days, even if we had permission for 2 weeks. If we were late coming back, we had to enter a jail cell. If the returning person did not return, their guarantor had to enter the repentance room. Even if we came back late after all, the guarantor still could not leave the room. It was like a prison: There was a high concrete wall with two cages in it. The repentance room was next to the cage and had a tatami mat. I didn’t want to enter the cage, so I came back by the appointed time. | \n
In 1941, one male who was a former soldier came back late, and the staff chased and caught him, and hit his body with stones while he hung from his arms and legs. I saw it from the girls’ room. I was disgusted and afraid, because they hit his head with a stone. | \n
(Omission of middle part) | \n
I think my enforced isolation was not severe, and I lived a long time by entering this leprosarium. There was a little benefit to the law. The law was abolished at1996. After abolishing the law, since all the survivors don’t have | \n
I think patients’ families feel better about not having to worry about appearing in public with patients, because the law was abolished and we are without the offending bacteria. Although there are many survivors without family, like me. | \n
Listener: Since this narrative will be published, what else do you want to say? | \n
Mrs.Kadowaki: Although I am not certain, there may be new patients in the future, and I hope these future patients and their families can live ordinary live without difficulties, because in the past, the families had many difficulties. At the time, I was only a child when I got Hansen’s disease, and my family was very worried about public appearances. Our surroundings were a real worry to a small patient’s mother, who went crazy with worry. There was a family that had several patients in one family; how painful that must have been for the family. It was very hard for us with only one patient in the family. Although the law was abolished, we cannot return to our hometowns, but at least now we can be treated humanely. We hope sincerely that our families can live in society with peace of mind. | \n
This next story is about how I lost my eyesight. I had a high fever due to erythema nodosum leprosum, which I got the year after I entered the leprosarium. I was very tired from caring for several severe patients as my enforced labor, and I was hospitalized several times. Because I was not getting proper treatment for | \n
Before the war, we tried a new drug because the chief of the leprosarium heard good things, but it backfired, and many patients died from the side effects. I did not die, but the disease progression was getting worse. I would soon need a tracheotomy, and most importantly, I lost my hair. I was 20 years old and felt very pitiful. | \n
As my condition was getting worse, I thought I would die if I didn’t have a strong mind. Promin come to our country in 1948. At first I did not hope, because I had learned my lesson from the former side effects, but now I think I was foolish not to hope. The next year I used Promin and got better and lost the edema in my face, limbs, and larynx. I escaped having a tracheotomy, my wounds healed, and my complexion got better. These good times continued for 3 or 4 years. | \n
Around 1953, we started a new medical treatment using drugs for | \n
The side effects were very terrible, although I did not take large amounts of the drug, but the condition of my disease got worse again, and I lost my eyesight in both eyes for half a year. At first, my visual power decreased; next I could not open eyes because of the dazzling light and my pupils had become small like the point of a needle. I fell into a dense fog. I had pain in my eyes, but I did not feel the pain, because I was more sad for my lost eyesight. Then I lost my eyesight completely. | \n
Slowly my eyesight got better, but then I started vomiting and I had to have enucleation of the eyeball. I was very sad. Now I cannot even wear a glass eye because of lagophathalmos, so I do not have eyeballs. If I still had my eyeballs now, I could still hope for a recovery of my visual power, but I do not have hope that medical treatment could develop new eyeballs. As a side effect, my condition rapidly got worse. My face got ugly. When my parents came to see me, they were surprised and backed away. You (listener) were surprised to see such severe sequalae when you started working here. I heard they took out my eyeballs because of glaucoma, though the doctor did not say it. The doctor did not measure the intraocular pressure, he just pushed the eyeball by hand. Although there was treatment for glaucoma at that time, the doctor’s concern was only for new treatment of Hansen’s disease. | \n
I fell down to the bottom of hell when I lost my eyesight. I felt as if I were dead; I call it feeling hell on earth, with how painful it was. My friends, husband, and the association of blind people supported me for a long time. Now that my friends and husband are dead, I feel so obliged to them. When I was hospitalized, my husband cooked and encouraged me to eat. People around us said, “It is very pitiable that he has to take care of a blind wife.” Losing my eyesight was sad for him, too. He took care of me though, so that I could live a long life. In 2008, he had kidney disease and hemodialysis and said, “Because I cannot eat my favorite foods, life is not as pleasant.” I pitied him, but he endured for 3 years. Maybe he was preparing me to lose my husband for those 3 years. So when he died, I could endure it without crying in front of everyone, persuading myself to believe “He is still alive.” | \n
When I had good eyesight, I liked sewing, and made protectors for handicapped people to prevent wounds, and cotton work gloves with only one finger. I have lived 58 years without eyesight, and I can go to the bathroom and everywhere else by using my mouth. My hands can feel nothing, due to sensory nerve paralysis. It is as if I had burn wounds. My feet are the same. My mouth is the only part I have left that can still feel. So I wear a cloth over my mouth when I use the toilet and check for the button using my mouth. | \n
Part of the life of Ms. Hanako Kadowaki.
Source: Transferred and modified from: Makiko kondo, Oshima Seisho-en: Life review of Hansen’s disease survivors living in Oshima Seisho-en, 423–442, Kazama shobo, Tokyo, 2015.
Hansen’s disease, also known as leprosy, is an infection caused by
In Japan, there were many Hansen’s disease patients before the end of World War II. Many of them could not live in their hometowns, so they became homeless or were forcibly placed in leprosaria with the passing of the Leprosy Prevention Law. Unfortunately, World War II was a time of national crisis in Japan, and many patients in leprosaria were treated with little regard for their dignity and human rights. In addition, many Hansen’s disease survivors never had the opportunity to return to general society and had to live out their lives in sanatoriums, because the Leprosy Prevention Law, which declared that Hansen’s disease patients must be isolated for their entire lives, has only recently been abolished.
\nIt is important to learn from the experiences of Hansen’s disease survivors, whose rights have been threatened through the violation of bioethical principles. In addition, elderly survivors have acquired valuable knowledge by surviving extreme situations, which can help us solve problems in the future. Today, the average age of survivors in Japan is 82, and they live in 13 national sanatoriums. When they pass away, we will lose their stories. It is important to record their experiences of suffering, along with their wisdom.
\nWe are working on continued research on nursing practices for survivors. This study explores the bioethical implications of survivors’ experiences. In the second section, we discuss the lessons we can learn from their experiences. In the third section, we share the insight they have acquired by living through hardship and discuss how to genuinely restore their rights, considering that their dignity has been threatened. In the fourth section, we discuss current issues affecting survivors and how our work needs to embody the principles of bioethics through nursing practices. In the final section, we summarize what we have learned from the survivors’ experiences.
\nThe first characteristic [3, 4] of Hansen’s disease is that the peripheral nerves are invaded, and the skin of the legs, hands, and face is deformed because the optimum temperature of the
The second feature [3, 4] consists of the multiple symptoms caused by peripheral nerve damage. These symptoms are conspicuous and cause curiosity in non-afflicted individuals. Sequelae remain throughout a survivor’s life and greatly impact their quality of life, even today. Sequelae include: the inability to feel pain or notice injuries due to sensory nerve paralysis; infections from general bacteria caused by an external wound that can result in cellulitis, sequestrum, and even limb loss; motor nerve paralysis due to hand or leg deformations such as drooping hand, monkey hand, claw hand, drooping leg, and claw toe; facial nerve paralysis such as lagophthalmos, drooping eyebrows and eyelids, drooping lips, and deformation of the lips; atrophy of the nasal septum and nasal choncha, resulting in nose deformations such as saddle nose or flat nose; easily injured corneas due to lagophthalmoses, the inability to close the eye, caused by facial nerve paralysis; loss of sensitivity within the cornea due to the trigeminal nerve’s inability to feel pain, which can eventually cause blindness; iridocyclitis (i.e., inflammation of the iris) can lead to blindness and eventual enucleation of the eyeball; and finally, autonomic nerve disorders can cause sweating disorders, problems with heat retention, and neuralgia in the head and face. These sequelae cause additional pain and suffering for patients.
\nTreatment of Hansen’s disease with Promin began in the USA in 1943. In Japan, Dr. MorizoIshidate succeeded in producing Promin 1 year after World War II ended [5]. Today, the World Health Organization (WHO) promotes combination chemotherapy in terms of treating Hansen’s disease [6]. Since Promin was developed, patients can achieve complete recovery without any sequelae.
\nHistorically, Hansen’s disease [7, 8] has been one of the most frightening ailments around and was stigmatized throughout the ancient world. It appeared in the oldest civilizations of China, Egypt, and India. The first known written reference to leprosy appeared on an Egyptian papyrus document written around 1550 BC. In Japan, it was described in numerous ancient texts such as
In Japanese history, patients withdrew into their homes so as not to stand out, or they coexisted with the lower classes. If they could not live in their hometowns, they often traveled on pilgrimages and slept under the eaves of shrines and temples; they had to beg because they were homeless. For example, there are 88 temples along the1200 km pilgrimage route on the island of Shikoku. Pilgrims start at the first temple until they arrive at the 88th and then return to the first one. Since the Buddhist high priest Kukai made this journey in the nineth century, pilgrims thought they were working with him at a spiritual level. People living on Shikoku thought pilgrims were an incarnation of Kukai and delightedly gave them charity. If pilgrims died by the roadside, local people buried them.
\nDr. Armauer Hansen first discovered the pathogenic bacteria
With World War II coming, Japan faced a national crisis as modernization picked up and wealth and military strength increased. With the outbreak of war, Hansen’s disease was regarded as a national disgrace. This is because (1) homeless, begging, and wandering patients were a symbol of Japan not being a civilized country; (2) based on ideas of ethnic cleansing, weak individuals (such as those with low intelligence or schizophrenia, those who were physically disabled, and those who had Hansen’s disease or tuberculosis) were ostracized; and (3) since Hansen’s disease occurred frequently in young males, these patients could not become soldiers and contribute to the nation’s military force. As a result, Hansen’s disease was viewed as a terrifying epidemic and national disgrace, and the government proceeded to enforce policies of lifelong confinement and isolation [11, 12].
\nThe Leprosy Prevention Law was renewed in 1953 (Act No. 24, new Rai-yobo-ho), even though the National Leprosaria Residents’ Council (ZenkokuKokuritsu Rai Ryoyo-shoKanjyaKyogikai) opposed it on the grounds that lifelong isolation threatened patients’ human rights [13, 14]. By this point, World War II was over, reconstruction under a new democratic constitution was under way, Promin had been developed, the illness could now be cured, and the WHO recommended that the government reconsider its segregation policy.
\nThe Leprosy Prevention Law was renewed in 1953 with the addendum, “We must reconsider this policy as soon as possible” [15]. However, the law remained in place until 1996, although legal regulations were alleviated through patients’ efforts. Patients created self-government associations at each leprosarium, which cooperated with all other leprosaria and negotiated with the Ministry of Health, Labor, and Welfare. In the 1950s, they obtained much-needed medical treatment and pensions for all patients. They ended requirements for patient labor and began employing leprosarium staff in the 1960s, and improved housing for patients in the 1970s. Patient living conditions got better gradually, but these improvements had long been needed [13, 14, 16].
\nIn 1996, the Leprosy Prevention Law was finally abolished. Survivors won a lawsuit striking down national indemnity, and the court convicted the Japanese government of enacting an unconstitutional law. The nation officially apologized, with formal apologies from the Prime Minister, the National Diet, the Minister of Health, Labor, and Welfare, and the Chief Justice of the Supreme Court. In 2009, the government established a new law, the Act to Accelerate the Resolution of Problems of Hansen’s Disease (Act No. 82, Hansenbyomondai no kaiketsu no sokusin ni kansuru horitsu). The new legislation guaranteed that survivors could live at the remaining sanatoria for the rest of their lives, would be given a comfortable life and medical care, would be aided in their social lives and rehabilitated into mainstream society, receive help to restore their reputations, be buried with dignity, and that their relatives would also be supported [17].
\nAlthough the treatment of Hansen’s disease patients has slowly improved, it was inhumane from the time that the first Japanese leprosarium opened in 1907 until the end of World War II [13, 14, 18]. For example:
\nIn the early days, the director of a leprosarium was not only a doctor, but also a policeman. The police were in charge of enforcing confinement.
The Leprosy Prevention Law did not allow patients to leave the leprosaria, and they had to remain there their entire lives. Although the leprosaria were medical institutions, they also had crematoria, graveyards, and religious buildings (Figure 1).
In order to prevent patients from escaping, their property was converted into a currency that could only be used within the leprosaria.
When patients entered a leprosarium, they were compelled to take on a new name and could not use their real one.
The chief of a leprosarium had a great deal of power, and if patients did not obey the rules or resisted authority, the chief could punish them or send them to solitary confinement at his own discretion.
Patients were permitted to marry, but not to have children. Before any marriage could take place between patients, the male was required to have a vasectomy.
When patients entered a leprosarium, they had to sign a letter that stated they accepted to be dissected after death. Figure 2 shows an artistic depiction of a dissection table used in certain leprosaria. This table was thrown into the sea, but washed back up on shore. Now, the table is on display on the island as a symbol of human rights violations.
In order to operate leprosaria with as few doctors and nurses as possible, patients were required to work. In 1949, there were 62 doctors and 253 nurses in all leprosaria in the country, while there were 8318 patients. Patients worked various jobs such as caring for severely disabled patients, as medical assistants, conducting funerals for deceased patients, washing, working on engineering projects for the leprosaria, or carrying items for staff or disabled patients.
The space for patients and the area for those without Hansen’s disease were clearly divided. Patients could not enter the disease-free zone, and if a doctor needed to enter a patient’s home due to severe illness or injury, the doctor wore rubber boots, despite the Japanese custom of not wearing shoes inside the home.
There are graves of patients in spite of medical institution (Picture provided by Oshima Seisho-en©).
The dissection table used in certain leprosaria, which was thrown into the sea, but washed back up on shore (Illustration by Akika KONDO©).
In this section, we introduce our study [19], discuss the factors that caused patients to lose their limbs, and examine how patients’ daily lives were affected by this occurrence.
\n<Categories> | \nSubcategories | \n
---|---|
<1. Loss of pain as a caution> | \n(1) I moved too much, because I did not feel pain from my wounds | \n
(2) I could not notice a heavy burn, even if my skin was charred, because I felt numb | \n|
<2. Carrying loads in the same region> | \n(3) I protected a region of my body that was paralyzed and deformed, so I carried my loads at same region and caused new wounds | \n
<3. Collapsing from within the body> | \n(4) The bone went stale, and my finger disappeared | \n
\n | (5) A tumor mass from leprosy erthema nodosum was crushed naturally | \n
<4. Labor is vital because of poverty> | \n(6) Because I was poor, I could not live without working | \n
\n | (7) I could not miss work due to perennial wounds | \n
<5. Poor living conditions promoting worsening of wounds> | \n(8) Because we did not have transportation, I had to walk home from the treatment room, and the bandage came off immediately after treatment | \n
\n | (9) I was wounded easily, because I worked hard wearing wooden clogs on an unpaved road | \n
<6. Contaminated wounds and lack of hygiene> | \n(10) Because I could not avoid scrubbing, washing, and field work, my wound was contaminated immediately | \n
\n | (11) Because gauze, bandages, and drugs were too expensive, I did not have the means to disinfect my wounds when they were dirty from muddy work | \n
\n | (12) Tweezers and gauze were hard to get | \n
\n | (13) There were many flies in our food, and maggots breed in the wound | \n
<7. A poor medical system> | \n(14) Because there were many patients, I was too busy and could not wait to be seen by the doctor | \n
\n | (15) The doctor did not do house calls, even if we had a serious condition with a high fever or tumor mass from leprosy erythema nodosum | \n
\n | (16) Because there was no doctor, my wound was treated too late and got worse | \n
\n | (17) The doctor did not treat me like a human | \n
\n | (18) I had a bitter experience being experimented on, so I became timid of medicine | \n
<8. Inadequate treatment by untrained individuals> | \n(19) Patients did amateur wound treatment, so they weren’t treated correctly | \n
\n | (20) Because I did my wound treatment myself, it became infected | \n
<9. Superstition> | \n(21) Because I held the superstition, “If we cure perennial wounds, we will lose our eyesight,” I deliberately created new wounds | \n
This study uses aging survivors’ narratives to clarify why Hansen’s disease patients had repeated wounds, which led them to lose their limbs, and how they coped with these afflictions until starting Promin treatment. After starting to take Promin, patients no longer developed multiple severe disorders that resulted in new wounds or lost limbs, although they still had preexisting severe sequelae that continued to negatively influence their quality of life.
\n\n[Categories] | \nSubcategories | \n
---|---|
[A. Acquiring their own style of treatment for perennial wounds] | \n(a) I checked temperature of people or things with my tongue, which was the only part of my body that could feel hot or cold, as everything else had sensory nerve paralysis | \n
(b) Because my wound was small at surface, but was deep, I did not know how bad it was by looking at it, so I made a judgment whether I needed treatment or could use a bubble of hydrogen peroxide | \n|
(c) Before my wounds got worse, I started using my own style of wound treatment | \n|
(d) I scraped off necrotized parts of skin without mercy | \n|
(e) I burned tweezers in the fire of a candle and dug into the wound | \n|
(f) I stitched a crack in my skin at finger joint closed by sewing it with yarn myself | \n|
(g) I blended drugs to make effective drugs to either protect or remove skin | \n|
(h) I made drugs from horse teeth | \n|
(i) Because I did not have drugs, I beguiled my neuralgia by continuing to walk around during the middle of the night | \n|
(j) I protected the places that wounded easily | \n|
(k) I devised a way of walking in order to avoid creating a new wound | \n|
(l) I devised a way of not getting my wounds wet or dirty | \n|
(m) I stretched and fixed crooked fingers, in order to prevent blood blisters | \n|
[B. Not being able to cure wounds by slack treatment] | \n(n) I knew I could not be cured by slack treatment | \n
(o) I was particular about my own style of treatment | \n|
[C. Selecting a therapist based on the severity of the wound] | \n(p) I went to the doctor only when my wound was beyond the control of the patients | \n
(q) I relied on the nurses, who were getting used to wound treatment, had good skills, and were improving their skills by evaluating the patients | \n|
(r) Patients managed all medical treatments | \n|
[D. Relieving suffering through limb amputation] | \n(s) I allowed my wound treatment to cause atrophy | \n
(t) I selected cutting off a hand, foot, or finger in order to relieve suffering in the wound | \n|
[E. Giving priority to labor, and even choosing to cut off limbs] | \n(u) I selected cutting off a limb in order to continue working and sustain the lives of my wife and children who live outside of the leprosarium | \n
(v) I had no choice but to work in order to sustain my own life, so I selected cutting off my own limb | \n|
[F. Keeping a limb due to not being able to work or having a work release] | \n(w) My limbs remain because I could not work due to lost eyesight or neuralgia | \n
\n | (x) I was supplied from home, so I did not need to work. Thus, my limbs remained | \n
Since Promin was developed during World War II and didn’t arrive in Japan until after the war ended, severe sequelae occurred when the entire nation was suffering from the effects of poverty. Our results show that limb loss during this period was caused not only by pathological characteristics such as sensory and motor nerve paralysis in the limbs, but also by a shortage of proper medical care and hygiene, in addition to economic distress. The findings show how patients lived with Hansen’s disease and what multiple severe disorders, wounds, and limb loss meant to patients living in poverty.
\nNarrative data were obtained from ten survivors and analyzed using a qualitative and inductive method. The average age of the survivors interviewed was 81.8 ± 2.7. Nine individuals had the lepromatous disease type, while one person had the tuberculoid type. Eight individuals had limb deficiencies, nine had hand and leg drooping, three were blind, and all ten had both contracture and neuralgia.
\nThere were nine main causes of repeated wounds (see Table 2) and six main ways of coping with them (see Table 3). Figure 3 shows the relationships between the cause categories and coping categories, and reveals that there were three
The cycle of repeated wounds among Hansen’s disease survivors. Transferred from: Yamaberi et al. [
Hansen’s disease patients were wounded easily due to <1. loss of pain; pain signals that a person is hurt> and repeatedly <2. carrying loads in the same region > to compensate for other deformities or paralysis. However, patients also believed that <4. labor is vital because of poverty>. They continued to work under these circumstances, leading to increased external lesions. Furthermore, due to <5. poor living conditions that worsen wounds>, <6. contaminated wounds and a lack of hygiene>, a <7. poor medical system>, and <8. inadequate treatment by untrained individuals>, existing infections got worse or became infected, wounded areas were not treated or allowed to heal properly, new wounds formed, and limbs deteriorated until they finally <3. collapsed from within the body>. However, many patients continued to [E. give priority to labor, even choosing to cut off their own limbs], and kept working in spite of their wounds, due to <1. loss of pain>. Thus, their wounds became worse, and they fell into a negative spiral. On the other hand, some patients were afraid to lose their eyesight and believed in <9. superstition>, such as: “If you recover from your wounds, you will lose your eyesight.” These patients created new wounds on their bodies to avoid fully healing and thus not lose their eyesight. No matter the causes of repeated wounds, it led patients to fall into a negative spiral of deteriorating lesions.
\nSince patients fell into these negative spirals, having lesions was a matter of course, so they called them “perennial wounds.” They knew empirically that they [B. could not cure their wounds with slack treatment], so they [A. acquired their own style of treatment for perennial wounds] and routinely attempted to heal themselves. If patients required specific medical treatment, they [C. selected a therapist based on the severity of the wound]. For example, when more severe wounds required cutting off a large bone, patients sought a doctor’s help. If a less severe wound required cutting off a small bone at the finger or toe, they often cut it off by themselves or went to a nurse. Thus, patients made decisions about and arrangements for treatment themselves. They received support from nurses, except in cases of intractable severe gashes, when they sought the aid of doctors. With these coping techniques, patients barely maintained their lives in severe poverty, continuing to [E. give priority to labor, even choosing to cut off their own limbs]. Thus, they lived with “perennial wounds.”
\nAlthough patients could cope with ordinary external wounds by [A. acquiring their own style of treatment for perennial wounds], the wounds <3. collapsing from within the body> were intractable, and they [B. could not cure their wounds with slack treatment]. Patients often chose to amputate limbs to return to work more quickly and easily; they had to work hard to support themselves or send money back to their wives and children who lived outside the leprosarium. Others hoped amputation would [D. relieve their suffering]. On the other hand, when patients could not work (e.g., due to loss of eyesight), the negative spiral was broken. As a result, patients [F. kept their limbs due to not being able to work or having a work release]. Both the loss of eyesight and cutoff limbs meant that patients would live with severe sequelae as compensation to survive poverty.
\nAbove, we introduced historical facts about the Hansen’s disease isolation policy and showed why and how patients contracted multiple severe sequelae. In this section, we will discuss what lessons we learned (see Table 4).
\n\n | ||||||||
\n | ||||||||
(1) Enforced confinement and lifelong isolation | \n\n | |||||||
\n | Enforced confinement | \n・ | \nProtecting homeless patients in leprosarium | \nー | \nー | \n・ | \nProtect people in crises (such as the homeless) | \nbeneficence | \n
\n | ・ | \nFinding patients in their homes, and enforcing confinement using police power | \nExercising compelling power (depriving freedom of decision-making) | \nRespect for autonomy | \n\n | ー | \nー | \n|
\n | ・ | \nBuilding leprosaria in hard-to-reach places in order to prevent patients’ escape | \nExercising compelling power (depriving freedom of decision-making) | \nRespect for autonomy | \n\n | ー | \nー | \n|
\n | Lifelong isolation | \n・ | \nSeparating patients from their families | \nPlundering good (living with their family) from the patient’s life | \nNon-maleficence | \n\n | ー | \nー | \n
\n | ・ | \nPlundering their right to live in society | \nPlundering the opportunity to contribute to society or the family | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nCausing emotional suffering and thoughts of suicide | \nCreating existential suffering | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nActual harm done to families: by patients’ forced isolation, the family lost to live with their husband/wife, son/daughter, father/mother, brother/sister, etc. If patient was sustained family\'s life by his income, the family had difficulties with economy. | \nPlundering good (living with family, income) from a family | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | Isolation based on weak medical evidence | \n・ | \nEnforced confinement for a disease with weak infection power and little need for isolation | \nImpelling unnecessary isolation (physical restraint) | \nNon-maleficence | \n\n | ー | \nー | \n
\n | ・ | \nPrioritizing the nation’s convenience over patients’ needs without sound medical evidence | \nNeglecting the principle of medical care which determines the necessity of hospitalization based on patients’ medical condition | \nBeneficence | \n\n | ー | \nー | \n|
\n | Patients shouldering this burden unilaterally | \n・ | \nThe burden of isolation was solely on patients in order to prioritize the nation’s needs to prevent infection, empower the wartime regime, and enhance the national reputation | \nImposed burden only on patients due to national policy | \nJustice and/or equality | \n\n | ー | \nー | \n
\n | ・ | \nPatients endured lifelong isolation to protect the general public from infection | \nImposed burden only on patients in order to control infection. | \nJustice and/or equality | \n\n | ー | \nー | \n|
\n | Failing to abolish the Leprosy Prevention Law | \n・ | \nBy fighting patients’ association against government, they were permitted temporary going out, but they must prove to disappear mycobacterium leprae into their body and got permission to going out from head of leprosaria. | \nー | \nー | \n・ | \nDefend individuals’ freedom of action through flexible application of the law | \nbeneficence | \n
\n | ・ | \nThe government took many years to abolish an unnecessary law that violated human rights | \nNo one in law, medicine, or administration took action | \nBeneficence | \n\n | ー | \nー | \n|
\n | ・ | \nDue to this law, survivors continue to suffer from the old isolation policy | \nThey continued to suffer unnecessarily | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nPatients lost years of opportunity to come back into society, and survivors were elderly when the law was finally abolished | \nPlundering the good of living in society | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | Forming negative public opinion | \n・ | \nThe leprosaria protected patients from discrimination and persecution | \nー | \nNon-maleficence | \n・ | \nUse national power to protect the weak from harm, persecution, and discrimination | \nbeneficence | \n
\n | ・ | \nPromoted discrimination and persecution against Hansen’s disease patients among the general population through the campaigns to find patients in their homes and forcibly send them to leprosaria | \nPromote suffering and discrimination) indirectly | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nSpread discrimination and persecution from patients to their families, due to the campaigns to find patients in their homes and forcibly send them to leprosaria | \nSpread suffering and discrimination for family and relatives of patients | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | Avoid spreading information about the living conditions of patients to the public | \n・ | \nThe general public did not know about the poor conditions within the leprosaria | \nThe public did not have the opportunity to get important information and make decisions based on good, common sense | \nBeneficence | \n\n | ー | \nー | \n
(2) Poor treatment of patients in leprosaria (a) Direct threats | \n\n | |||||||
\n | Vasectomy and abortion | \n・ | \nAbortion | \nPlundering the life of a child | \nNon-maleficence | \n\n | ー | \nー | \n
\n | ・ | \nChild bearing was not allowed | \nPlundering good from a patient’s life, such as becoming a parent, the delight of child bearing, and enjoying old age surrounded by child and offspring | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nPatients were not allowed to refuse this treatment | \nExercising compelling power and depriving freedom of choice | \nRespect for autonomy | \n\n | ー | \nー | \n|
\n | ・ | \nSorrow for the loss of a child, sense of humiliation, and shame for the treatment | \nPsychological laceration | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nThe invasive operation itself | \nPhysical laceration | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | Pathological dissection | \n・ | \nWhen entering the leprosarium, all patients were required to sign a consent form permitting dissection after death | \nExercising compelling power and depriving freedom of choice | \nRespect for autonomy | \n\n | ー | \nー | \n
\n | ・ | \nDesecration of the dead | \nHarm the dignity of the dead | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nMedical contribution | \nー | \nー | \n・ | \nElucidate pathological cause of disease | \nbeneficence | \n|
\n | Chief at leprosarium held strong power | \n・ | \nPatients had to comply with the chief’s orders | \nExercising compelling power and depriving freedom of choice | \nRespect for autonomy | \n\n | ー | \nー | \n
\n | ・ | \nPunishment resulting in physical pain | \nCausing physical pain | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nPunishment resulting in weakness or death | \nPlundering a patient’s life | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nThis power was a warning to other patients, in order that they submit to orders meekly | \nExercising compelling power and plundering self-motivation from the majority of patients | \nRespect for autonomy | \n\n | ー | \nー | \n|
\n | Enforced exchange of property to money that could only be used in the leprosarium | \n・ | \nForfeiture of property | \nPlunder economic power | \nNon-maleficence | \n\n | ー | \nー | \n
\n | ・ | \nPreventing escape by depriving patients of cash | \nExercising compelling power and depriving freedom of choice | \nRespect for autonomy | \n\n | ー | \nー | \n|
\n | Enforced adoption of a new name and giving up one’s real name | \n・ | \nForfeiture of one’s own name | \nForfeiture of the social life patients had prior to entering the leprosarium and erasing the patient from society | \nNon-maleficence | \n\n | ー | \nー | \n
\n | ・ | \nDenying patients their identity | \nDenying personal uniqueness and individuality | \nRespect for autonomy | \n\n | ー | \nー | \n|
\n | Dividing the leprosaria between patient areas and healthy person areas | \n・ | \nDiscriminatory treatment between patients and staff | \nCause suffering through discriminatory treatment | \nNon-maleficence | \n\n | ー | \nー | \n
\n | ・ | \nThe purpose of the division was to prevent infection of the medical staff | \nー | \nー | \n・ | \nInfection control | \nbeneficence not for the patient, but for medical staff | \n|
\n | Enforced labor | \n・ | \nPatients did not have the right of refuse | \nExercising compelling power and depriving freedom of choice | \nRespect for autonomy | \n\n | ー | \nー | \n
\n | ・ | \nHeavy physical labor | \nCausing physical pain | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nPoor wages for hard work | \nUnfair exploitation | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nThe leprosarium was not able to sustain itself without patients’ labor | \nOnly patients had to shoulder the burden of sustaining the leprosarium | \nJustice and/or equality | \n\n | ー | \nー | \n|
\n | ・ | \nPatients were not given suitable care but were used as a labor force | \nReceived poor medical treatment | \nBeneficence | \n\n | ー | \nー | \n|
(b) Indirect threats | \n\n | |||||||
\n | Conditions caused multiple severe sequalae | \n・ | \nThe main cause of limb loss was the pathological characteristics of Hansen’s disease | \nー | \nー | \n・ | \nLimb loss was unavoidable due to the pathological characteristics of the disease | \nnon-maleficence | \n
\n | ・ | \nSevere poverty meant the patients could not live without working, even with wounds | \nIntentional, willful negligence | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | ・ | \nEven with lost limbs, patients had to work. The only exceptions were for the blind or individuals with another severe medical condition | \nPatients could not chose to rest their own bodies, except when they had a severe medical condition | \nRespect for autonomy | \n\n | ー | \nー | \n|
\n | ・ | \nPoor infrastructure and an unclean environment in caused wounds to worsen and patients to lose limbs | \nPoor physical environment did not protect from mixed infection and additional wounds | \nBeneficence | \n\n | ー | \nー | \n|
\n | ・ | \nThere was shortage of medical staff and goods | \nReceived poor medical treatment | \nBeneficence | \n\n | ー | \nー | \n|
\n | ・ | \nNew drugs were before there was evidence of their therapeutic effect, so more sequalae occurred | \nNon-therapeutic drugs were tested on the human body | \nNon-maleficence | \n\n | A cure was eventually developed with new drugs | \nbeneficence | \n|
\n | ・ | \nThe entire nation struggled with poverty, war, and earthquakes | \nー | \nー | \n・ | \nThe bad environment was unavoidable, considering social situation at that time | \njustice and/or equality | \n|
\n | ・ | \nMultiple severe sequalae caused by enforced work continues to decrease patients QOL even no. | \nCausing lifelong, irreversible harm | \nNon-maleficence | \n\n | ー | \nー | \n|
\n | Creating negative public opinion | \n・ | \nPatients’ changing appearance was a source of discrimination and was encouraged by the government’s policy | \nPromoting harm through discrimination | \nNon-maleficence | \n\n | ー | \nー | \n
The mistakes of isolation policy for Hansen’s disease patients through the four bioethical principles.
The foundation of biomedical ethics goes back to the Hippocratic Oath in BC 54. After World War II, the Nuremberg Code was created in 1947, following the consequences of the war and the Holocaust caused by the Nazis; this set of research ethics was developed to protect subjects’ will and freedom in future medical studies [20]. In 1964, the World Medical Association (WMA) announced the Declaration of Helsinki, which outlines rules of medical research as based on the Nuremberg Code; it continued to revision [21]. In 1979, the Belmont Report was created by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and illustrates principles of medical ethics to protect research subjects [22]. The WMA announced the Declaration of Lisbon in 1981, which describes patients’ rights [23]. The Council for International Organizations of Medical Sciences (CIOMS) created the International Guidelines of Biomedical Research Ethics in 2002 [24]. The Belmont Report clarifies biomedical ethics principles such as respect for people, informed consent, beneficence (i.e., evaluating benefits and risks), and justice (selecting subjects). The creation of biomedical ethics placed limits on human experiments and spread throughout the research world and medical practice.
\nJapan has a long history of medical knowledge, skills, and ethics. The medical book
The four bioethical principles are fundamental rules meant to address and resolve ethical issues in medicine. The first tenet is respect for autonomy, meaning that we must respect a patient’s autonomous decision-making and to remember that informed consent is important in every situation. This belief requires that medical professionals: (1) tell the truth, (2) protect others’ privacy, (3) adhere to the duty of confidentiality, (4) obtain informed consent for any kind of physical invasion, and (5) if asked, help the patient make important decisions. The second principle is beneficence, meaning that we must act for the benefit of others. This notion requires that we: (1) advocate for the rights of others, (2) protect others from harm, (3) remove risks that could cause harm, (4) support disabled persons, and (5) help individuals who are facing a crisis. The third rule of non-maleficence prohibits doing harm to others. This principle covers the following rules: (1) do not kill, (2) do not cause pain or suffering, (3) do not hinder another’s ability, (4) do not create discomfort for others, and (5) do not steal or destroy the good in another’s life. The fourth tenet of justice and/or equality means that social benefits and burdens must be distributed equally. This value requires that medical professionals distribute limited medical resources (such as manpower, goods, or capital) equally. We must avoid baseless discrimination and adequately balance competing requirements.
\nEnforced confinement threatened respect for personal autonomy because the government used its power via the police to compel patients to enter leprosaria and prevent them from escaping. On the other hand, homeless, wandering patients who entered leprosaria experienced a more comfortable life and improved medical care than they had previously; in this way, the leprosaria contributed to beneficence for some patients.
\nLifelong isolation threatened non-maleficence because patients were denied the happiness of living with their families and exerting their own abilities in society. Patients’ families were robbed of important family members and of patients’ contributions to the families’ incomes; family members could not live with patients throughout their lives, and if a male patient formerly supported his wife and child, his family lost income after he entered a leprosarium.
\nIn addition, because the required isolation was based on weak medical evidence, it also threatened non-maleficence in the sense that patients had to endure unnecessary seclusion, even though Hansen’s disease was not highly infectious. It also endangered beneficence because the country’s circumstances—namely the idea that Hansen’s disease patients were a national disgrace and not acceptable potential soldiers for the war effort—preceded medical requirements. Patients shouldered the burden of lifelong isolation in order to fulfill the nation’s policy of controlling infection, and the rights of the state were considered more important than those of patients; thus, justice and/or equality was also breached.
\nDelaying in nullification of the Leprosy Prevention Law violated beneficence because no one in the fields of law, medicine, or local and national government took action to change this regulation for a long time. However, operational relaxation of the law did allow patients to leave the leprosaria occasionally and contributed to beneficence a little. By delaying abolishment of the law, non-maleficence was violated because patients continued to suffer unnecessary isolation. They also lost years of opportunity to come back to general society. When the law was finally annulled, the remaining patients were almost all elderly.
\nEnforced confinement by police and the campaign to send patients to leprosaria influenced public opinion and promoted fear of the illness. It led the general public to expel patients from communities and caused families to discriminate against their sick relatives, even though entering leprosaria was supposed to protect patients from public prejudice and persecution. All of this violated non-maleficence.
\nThe lack of information about the realities of life within leprosaria also jeopardized beneficence. Except for some supporters, the general public did not know about or concern themselves with leprosaria, even though many people came into leprosaria and interacted with survivors after supporting the Leprosy Prevention Law. After World War II, Japan rapidly developed both economically and democratically. If more citizens had known about the conditions within leprosaria and the history of Hansen’s disease, there may have been many more advocates for patients.
\nOften, treating patients in leprosaria threatened their rights either directly or indirectly.
\nVasectomies were enforced for men prior to getting married, and pregnant wives were forced to abort their children, which directly violated non-maleficence because these actions either prevented a fetus from becoming a child (which goes against the principle “do not kill”) or took away patients’ delight in becoming parents and the joy in being surrounded by children in old age. These actions caused patients to suffer the loss of being able to have children and often a sense of shame and humiliation in having such invasive operations. These surgeries also endangered respect for autonomy because patients could not refuse them.
\nWhen patients entered a leprosarium, they were required to sign a letter of acceptance regarding their dissection after death. They could not refuse. This violated respect for autonomy and non-maleficence. Even if patients refused to have their bodies dissected after passing away, their bodies were cut up anyway and their organs removed. They were not able to benefit from operations (e.g., to remove cancerous tumors). In Japan, funerals are very important rituals, and dissection without informed consent constitutes blasphemy. However, dissections did contribute to beneficence because they helped reveal the pathological cause of Hansen’s disease.
\nThe chief of a leprosarium had a great deal of power, including the ability to punish patients. This jeopardized non-maleficence because patients who did not obey the rules were imprisoned. Furthermore, this threatened respect for autonomy, because this kind of power not only violated the rights of individual patients, but also served to warn others against breaking the rules.
\nChanging patients’ property to a currency that was only used within the leprosaria threatened both respect for autonomy and non-maleficence. Regarding the violation of respect for autonomy, the goal of this action was to prevent patients from escaping by making sure they could not use their money in the real world if they did manage to flee. In terms of threatening non-maleficence, since property was essential to one’s social life, depriving patients of property made it impossible to have a normal social status.
\nForcing patients to assume a new name and not allowing them to use their real one threatened non-maleficence because it meant depriving patients of a social life and “erasing” them from society. It also violated respect for autonomy because prohibiting patients from using their real names deprived them of their identities and harmed their sense of individuality.
\nDividing leprosaria into areas for patients and healthy people threatened non-maleficence because it resulted in discriminatory treatment. While the purpose was to prevent medical staff and other healthy people from becoming infected, it only contributed to beneficence to help medical staff, but not patients.
\nEnforced, compulsory labor violated respect for autonomy and threatened non-maleficence because patients suffered physically during their labor and were not sufficiently rewarded for it. It threatened justice and/or equality because only the patients shouldered the burden of maintaining the leprosaria, and it endangered beneficence because the leprosaria did not provide sufficient medical services, despite being medical institutions.
\nIndirect threats to Hansen’s disease patients promoted multiple severe sequelae. In our study (see above), the main causes of repeated wounds were the loss of pain and severe poverty, while the main sub-causes were poor living conditions, a lack of proper hygiene, and a deficient medical system. Prior to World War II, there was no silver bullet to cure Hansen’s disease, and the characteristics of the illness caused patients to easily develop repeated lesions. Thus, we cannot conclude that multiple severe sequelae threatened non-maleficence. However, doctors could clearly foresee that if patients were forced to work hard, they would have repeated wounds and would be forced to cut off limbs. In spite of this, the government still compelled patients to live and work in extreme poverty and did not give them the chance to rest and recover from their injuries. This situation threatened both non-maleficence and respect for autonomy. In addition, by not providing a physical environment or suitable medical care to prevent mixed infections and protect wounds, beneficence was violated. Trying new drugs on patients did contribute to beneficence by offering hope for a cure, but without evidence of any therapeutic effects or informed consent, patients continued to experience severe sequelae, thus endangering non-maleficence. Patients still suffer from multiple, irreversible sequelae today, which negatively affects survivors’ quality of life; thus, non-maleficence continues to be violated today.
\nBy allowing policies that resulted in severe sequelae, the leprosaria also indirectly violated non-maleficence, because limbs <3. collapsing from within the body> caused by enforced work in poor conditions led people to discriminate against patients and fear their changing bodies.
\nThere were undoubtedly some humanistic doctors, nurses, and religious men and women in the old leprosaria who cured patients and cared for them with devotion. However, the government’s policy on Hansen’s disease patients was wrong. We have learned the following lessons from history:
\nWe must create systems to ensure that medical policies do not violate bioethical principles.
We must ensure that infection-prevention methods do not increase people’s fear, especially in cases of lethal and tragic diseases. For example, Ebola hemorrhagic fever could cause people to fear and ostracize patients.
We must accurately communicate the pathological causes of symptoms to the public; individuals are often stigmatized for symptoms that are considered unusual or mysterious. For example, limb loss by sequestrum can occur not only with Hansen’s disease, but also with diabetes and thromboangiitis obliterans.
The majority, not the persecuted minority, makes decisions about policy. If the majority is not concerned about how the minority is treated, discrimination and bullying can continue. Thus, we must ensure that the majority has correct and accurate information and that we foster a sense of justice so that persecution is not allowed to persist.
In the last section, we discussed the various violations of the four bioethical principles in medical policy regarding Hansen’s disease. In this section, we discuss how patients survived extreme situations, and what wisdom aging survivors can pass on to future generations. We explain how they survived in detail because we believe that in order to restore human rights, we need to understand survivors’ strength and resilience. Their wisdom can be seen as universal, for the benefit of all (see Table 5).
\nCategories | \nSubcategories | \n
---|---|
1. Sustaining everyday life through self-sufficiency | \n(1) There were water shortages and poor water quality, a shortage of food, poor living conditions, and information disruption | \n
(2) Patients called on all their wisdom and ingenuity in order to obtain clean drinking water, cash, and food | \n|
(3) Patients endured heavy work | \n|
(4) Patients reclaimed new land and water resources | \n|
2. The courage to survive extreme hardships | \n(5) Patients’ difficult situations did not weigh heavily on their minds, because they found joy and fun even in hard work | \n
(6) Patients without heavy sequalae enjoyed having youthfulness and energy | \n|
(7) Patients could appreciate that their difficulties were trivial, because some had previously experienced homelessness and the wandering life of a pilgrim | \n|
(8) Patients were not bothered by their severe poverty, because all residents were equally poor | \n|
3. Resourceful people coming together | \n(9) Patients had held a variety of occupation before entering the leprosarium. Patients were grouped by profession, specifically by professions that were needed to sustain the leprosarium | \n
(10) Professional patients taught their jobs to novice patients | \n|
(11) If there was no professional in their midst, all jobs were done by trial and error, with patients learning by imitation | \n|
(12) Some patients who had experienced homelessness and the wandering pilgrimage had excellent wisdom for everyone coping with severe poverty in the leprosarium | \n|
(13) Doctors treated patients equally based only on their medical judgment | \n|
4. Assembling self-sufficient organizations for self-defense | \n(14) There was physical and psychological distance from the leprosarium staff, who treated patients inhumanly. The government and leprosarium did little to help the patients | \n
(15) Patients created self-sufficient organizations, such as a young persons’ association, a vigilante corps, and a women’s association. The self-governing associations decided terms of payment based on the difficulty of a job, and they systematically prepared to receive pilgrim patients from outside | \n|
(16) Since all residents were assigned jobs, even children, the associations made sure that everyone was doing the appropriate job for his or her skills and abilities | \n|
(17) The patients’ organizations created systems to stockpile food and water | \n|
(18) They made rules about water use during times of scarcity | \n|
(19) If anyone did not follow the rules, a popular leader made sure they did | \n|
(20) When male doctors went away to fight in World War II and medical care was shorthanded, the patients undertook their own care | \n|
(21) Strolling players helped with shopping outside of the leprosarium and gifts from families living outside the leprosarium helped alleviate patients’ poverty | \n|
5. Patients created a mutualaid system | \n(22) Patients gathered a portion of all payments for enforced work and distributed it equally to patients who could not work due to severe sequalea such as lost eyesight or other critical conditions | \n
(23) They shared food and goods with everyone. If someone was in poor physical condition and could not work, somebody took their place | \n|
(24) They were considerate of weakest among them, such as girls who were ashamed of receiving charity or begging, or blind patients who hesitated to receive care from other patients. If an individual had food, they did not eat in front of patients without | \n|
(25) When blind patients received charity from working patients, they often gave the workers a massage as a sign of their gratitude | \n|
6. They agitated to compel the government to provide better support | \n(26) Some survivors decided to fight against the government and encourage the abolition of the Leprosy Prevention Law, deciding to once again be homeless and live in poverty | \n
\n | (27) After receiving better support from the government, the survivors’ daily lives improved dramatically | \n
Wisdom of aging Hansen’s disease survivors, who survived in extreme situations.
Source: Adapted from Ref. [30].
This study [30] used narrative data from aging survivors to clarify how patients survived in poverty before World War II. The subjects are living in the same sanatorium (mentioned in the above study), but that study specifically selected survivors who had repeated wounds and thus contained many people with the LL (Lepromatous) type. For this research, we focused on older survivors. The average age of our subjects was 84.3 years old, and the average age for all survivors living in this sanatorium was 80.2 year sold. The subjects had lived at the sanatorium for an average of 66.3 years, and all survivors in this particular sanatorium had lived there for an average of 52.6 years. We gathered data through semi-structured interviews and analyzed it using qualitative and inductive methodologies.
\nThe narrative data were integrated into six categories of coping methods and types of resourcefulness. < 1. Maintaining everyday life through self-sufficiency> showed that there were water shortages and poor water quality, a dearth of food, poor living conditions, and information disruption. They endured heavy labor, and reclaimed new cultivated land and water resources. They were self-sufficient and found ways of coping with a difficult daily life.
\n<2. The courage to survive extreme hardship> showed that patients’ difficult situations did not weigh heavily on their minds because they found joy and even fun in hard work. Those without grave sequelae had youthfulness and energy. Everyone could appreciate that their hardships were trivial compared to worse situations, because some patients had previously experienced homelessness and the wandering life of a pilgrim. Their severe poverty did not bother them because all residents were equally poor. This showed that these patients had the psychological strength to overcome hard labor, illness, poverty, and still have a positive outlook.
\nThe wisdom of <3. resourceful people coming together> was important because patients had held a variety of occupations prior to entering the leprosarium. Patients were grouped by profession, specifically by vocations that were needed to sustain the leprosarium. Professional patients taught their jobs to novice ones, and if there was no expert in their midst, all jobs were done by trial and error, with patients learning by imitation. Some patients who had experienced homelessness had excellent wisdom to share with everyone, who were coping with severe poverty in the leprosarium. In addition, doctors treated patients equally based solely on their medical judgment. They distributed extra food only to seriously ill patients. This meant that individuals with a great deal of insight into how to survive were gathered together in the leprosarium.
\n<4. Self-sufficient organizations for self-defense> were formed because there was both physical and psychological distance from the leprosarium staff, many of whom treated the patients inhumanely. Since the government and the leprosarium did not help them, the patients created self-sufficient organizations such as a youth association, a vigilante corps, and a women’s association. These self-governing associations determined salaries based on the difficulty of a given job and were systematically prepared to receive pilgrim patients from outside the leprosarium. Since all residents were assigned jobs, even children, the associations made sure that everyone was doing work suitable for their skills and abilities. The associations created a system to stockpile food and water and made decisions about water use during times of scarcity. If anyone did not follow the rules, a popular leader would make sure they did. During World War II, medical care was even more shorthanded than before because the leprosarium’s male doctor went away to war; only the female doctor was left, so patients undertook more of their own care. When traveling actor came to the leprosarium, they listened to patients’ requests and solved their issues the following day. In addition, gifts from families living outside the leprosarium helped alleviate patients’ poverty. This all shows that patients were self-sufficient and formed organizations within and networks outside the leprosarium.
\nPatients <5. created a mutualaid system> in order to gather a portion of all payments for compulsory labor and distribute them equally to patients who could not work due to severe sequelae (such as lost eyesight or other critical conditions). They shared food and goods with everyone, especially the weakest among them. If an individual was in poor physical condition and could not work, someone else took their place. The patients were considerate of girls who were ashamed to beg or receive charity and of blind patients who hesitated to receive care from other patients. If an individual had food, he did not eat in front of those without it. On the other hand, blind patients gave massages to workers as a sign of gratitude for their charity. They all worked to embody the ideal of “helping and loving each other.”
\nWhereas the above categories were most evident before and around World War II, much later the patients <6. fought to compel the government to provide better support>. They initially hesitated to fight the government and work toward abolishing the Leprosy Prevention Law because they feared being forcibly turned out of the leprosaria and returning to the discrimination and homelessness of their hometowns. However, after patients obtained the government’s support, their daily lives improved dramatically.
\nThe first two pieces of wisdom (<1. maintaining everyday life through self-sufficiency> and <2. the courage to survive extreme hardship>) showed that the patients had the self-sufficiency and psychological strength to cope with severe poverty. The next three pieces of wisdom (the importance of <3. resourceful people coming together>, <4. self-sufficient organizations for self-defense>, and <5. the creation of a mutualaid system>) demonstrated that, as a group, the patients had extraordinary coping abilities. Using these five categories, Hansen’s disease patients survived severe poverty up to and during World War II by forming a skilled community that had subsystems for self-sufficiency, self-defense, and mutualaid. Later, by <6. fighting to induce the government to provide better support>, they showed that their community had the strength and ability to cooperate with other leprosaria groups and fight against the government.
\nThe public ostracized Hansen’s disease patients, who lived with the stigma, that their illness was due to divine punishment or was a national disgrace. They coped by forming a skilled community and survived severe poverty. Their community had subsystems for self-sufficiency, self-defense, and social security. Their community functioned systemically and was headed by leaders who were hard workers with good morals. The patients were able to cope with severe poverty by themselves, without help from the government or the leprosaria. They maintained their autonomy. This revealed their strength, resilience,and dignity in fulfilling their own responsibilities, even when they suffered. They proved that they could function not only as individuals but also as a group. This is similar to Viktor Emil Frankl’s “attitude value,” Viktor Emil Frankl [31] developed in his book
In old age, the ego’s development task is to find integrity and avoid despair by acquiring wisdom [32]. Wisdom means being detached and transcending concerns about one’s own life before death, integrating life experiences, and learning how to pass these lessons on to future generations in spite of decreasing physical functions. Today, the average Hansen’s disease survivor in Japan is 82. The survivors have self-confidence and pride in having lived through severe poverty on their own, with little help from the government or medical staff. They are integrating their lives in end-of-life development tasks, and their extreme experiences produce heightened wisdom for posterity.
\nWe think the survivors’ knowledge has a universality that can provide suggestions for future difficulties, and is thus valuable for future generations. For example, in the Great East Japan earthquake and tsunami of 2011, many small, depopulated villages were isolated and could not obtain help from outside. The wisdom of the Hansen’s disease patients, specifically in forming skilled communities (with subsystems for self-sufficiency, self-defense, and mutualaid), suggests how isolated villages could heighten their community’s resiliency during a crisis. Furthermore, in order to survive in a chaotic society, their wisdom could be used as a business model to create strong teams whose members have good rapport with each other.
\nWhat would genuine restoration of survivors’ rights look like? Today, their severe experiences are used as a negative example in human rights education. While commendable, we think this is insufficient due to their past and present suffering. We believe that a real restoration of their rights would be utilizing their wisdom to solve future problems. Many people appreciate their knowledge and recognize its value, such as in the spread of logotherapy from Auschwitz. Thus, we hope to pass on not only the negative history of survivors’ experiences, but also their insight.
\nAbove, we discussed the violation of bioethical principles regarding the treatment of patients in leprosaria and the wisdom they gained from surviving extreme situations. In this section, we discuss current concerns for aging survivors and introduce ethical practices for the nurses who work with them.
\nToday, the average Hansen’s disease survivor in Japan is 82. There were a total of 1718 leprosaria residents in 2015 and 3286 in 2005. Almost all survivors will pass away within the next 10 years. Since former governments attempted to eliminate Hansen’s disease by forcing patients to live in lifelong seclusion and to have vasectomies and abortions, most survivors do not have children or grandchildren (except for those who had a spouse and children before entering the leprosaria). As a result, the history of Hansen’s disease in Japan will largely end with the death of the last survivor [33] (see Table 6).
\n\nSurvivors are now ensured a comfortable life in their remaining years, thanks to the Act to Accelerate the Resolution of Problems of Hansen’s Disease (2008 Act No. 82). As most survivors do not have families, sanatorium staff must care for them. With a decreasing number of survivors, the sanatoriums must now plan how they are going to maintain their facilities. Administrators of the sanatoriums are considering plans to keep them open, such as adding care for the general elderly population. Yet because old leprosaria were built in hard-to-reach places in order to prevent patients from escaping, planning for their future is now difficult.
\nMaintaining a sanatorium is expensive. For example, one sanatorium is located on a small island 8 km away from the mainland. This island is only accessible by ship. Even if there are only a small number of survivors, it will be necessary to transport medical, welfare, and clerical supplies by ship. In addition, buildings will need to be repaired.
\nWhen we think about cost-effectiveness in relation to the country’s tight financial situation, one option is eventually combining the 13 sanatoria into one facility. We must balance focusing on the most important goal—ensuring that survivors enjoy a high quality of life until the last one passes away—while also finding a solution to future problems.
\n\n\nThis study [33] was conducted at a sanatorium where a new building was constructed for survivors; they were relocated from the old terrace houses that dotted the island to a central nursing home for the elderly. Their former houses were too old and far apart, and nurses could not fully attend to their patients’ health. This study was based on interviews conducted with patients 6 months before their expected relocation to the sanatorium and was analyzed using qualitative and inductive methods. The results demonstrated the unique challenges facing Hansen’s disease survivors as compared to the general aging population (see Table 6).
\nCategory | \nSub category | \n
---|---|
1. The burden of house moving given the age-related decline in mobility and the community’s mutual aid abilities | \n1. Because the survivors are all aging, their ability to help each other is decreasing (e.g., due to the death of colleagues or spouses, and the decreased functioning of the survivors’ self-government association, as well as age-related decreases in individual physical function) | \n
2. Fear of increasing dementia and early death due to changing environment and overwork from relocation | \n|
3. Indeterminate anxiety due to the impossibility of imagining life after housemoving | \n|
4. Bitter memories of past of relocation | \n|
5. The burden of packing and damaging the living environment by carrying household goods | \n|
2. The burden of creating new strategies in order to live with multiple and severe sequelae in a new environment | \n6. Misgivings about being watched while eating among blind survivors who are embarrassed about eating messily | \n
7. The burden of living with blindness and sensory paralysis, and losing one’s mental map of one’s environment and having to create a new mental map of a new environment | \n|
8. Suffering the loss of a good residential environment that accommodated ones’ sequelae, neuralgia, thermal regulation disorder, and poor vision | \n|
9. Fear of increasing injuries that are liable to be more severe due to the loss of a living environment that had been adapted to accommodate hand and leg sensory disorders and prevent injuries | \n|
10. Loneliness and missing a comfortable residential and personal environment, while in one’s final abode | \n|
11. The increasing burden of caring for an aging blind spouse | \n|
3. The disagreeableness of having one’s life disturbed | \n12. Misgivings about being disturbed from a familiar daily rhythm built over a long time | \n
13. Concerns about being disturbed due to living near trouble makers | \n|
4. Dissatisfaction with the decision-making process managing building structure and room layout | \n14. Dissatisfaction about inconvenient building structure and room layout | \n
15. Anger and resignation about not being able to agree on the process of deciding on the structure of the new building | \n|
5. Thinking positively to accept relocation and enjoy the new environment | \n16. There is no anxiety about moving, if our requests are met | \n
\n | 17. All that is necessary is to enjoy a full and independent life before and after relocation | \n
The meaning of relocation for aging Hansen’s disease survivors.
Source: Transferred and modified from Ref. [33].
The various meanings of the upcoming relocation for aging survivors were integrated into five categories: <1. the burden of relocating from their old home to their new one given the age-related decline in mobility and the community’s mutualaid capacities>, <2. the burden of creating new strategies to live with multiple and severe sequelae in a new environment>, <3. the disagreeableness of having one’s life disturbed>, <4. dissatisfaction with the decision-making process for managing building structure and room layout>, and <5. thinking positively to accept relocating and enjoy the new environment>.
\nThe most important of these five categories are the first and second. The first one (<1. the burden of relocating from their old home to their new one given the age-related decline in mobility and the community’s mutualaid capacities>) shows the various meanings of aging, not just personal aging, but also community aging. The survivors’ community is comprised of old men and women because they were not permitted to have children. They have self-confidence due to having survived poverty and forming a skilled community (see Section 3); even after the government began providing further support, the self-governing committee continued to handle daily problems. With the aging and deaths of its members, the community weakened in its ability to cope and exert mobile power. Although residents recognize relocation will likely bring on dementia and hasten death, community aging is as much, if not more, a concern as personal aging.
\n\n\n\nThe second category of concern (<2. the burden of creating new strategies to live with multiple and severe sequelae in a new environment>) contains six subcategories: <6. misgivings about being watched while eating among blind survivors who are embarrassed about eating messily>, <7. the burden of living with blindness and sensory paralysis, and having to lose the mental map of one’s environment and create a new map of an unfamiliar setting>, <8. suffering the loss of a good residential environment that accommodated ones’ sequelae, neuralgia, thermal regulation disorder, and poor vision>, <9. fear of increasing injuries due to losing a living environment that had been adapted to accommodate hand and leg sensory disorders and prevent injuries>, <10. missing a comfortable residential and personal environment while in one’s final abode>, and <11. the increasing burden of caring for an aging blind spouse>.
\nThe second category shows how important the living environment is for survivors who have multiple severe sequelae. We previously introduced the causes behind repeated wounds and limb loss due to survivors’ past physical environment (see Section 2). Today, a survivor’s living environment is very important in alleviating sequelae. For example, patients with weak eyesight can recognize changing weather, the transition of the seasons, and the time of day from sunlight entering a window. Survivors with neuralgia alleviate overheating in the summer by using the wind from the sea, without increasing their pain. Thus, over the years, survivors have created suitable living arrangements in order to relieve the pain of their sequelae; relocating means losing their familiarity with their environment.
\nThe second most important aspect of this is the difficulty of redesigning the living environment in order to deal with conflicting or numerous conditions simultaneously, the goal being to mitigate the effects of multiple severe sequelae. For example, some survivors have sensory nerve anesthesia and have lost their eyesight. The general population of blind individuals cannot see, but can recognize items by touch. Hansen’s disease survivors who have lost their eyesight cannot recognize items by touching them. They have created a mental map of their environment through trial and error over time, often being wounded in the process, until they are able to move through their homes automatically. By relying on this mental map, survivors know their own position and direction within a space; with the help of a spouse who can see, or listening to the sound of the radio, or feeling a deep sensation of resistance from bumping into the wall, they can easily get around. If they have made a perfect mental map, they can move just as well as if they could see. Thus, forming a mental map is a way of adapting to numerous conditions simultaneously, which helps alleviate multiple severe sequelae. However, when relocating, survivors lose this mental map and must create a new one from scratch.
\nThe third most important aspect of the living environment is protecting the body from external wounds. Since survivors have lost their sense of pain, they do not notice when they have external lesions and their injuries can become severe. Survivors contrive ways to compensate for their sensory nerve paralysis and prevent wounds; relocating to a new environment increases the risk of getting hurt.
\nThe fourth way in which the living environment is important to survivors is that although Hansen’s disease causes various symptoms and survivors have multiple grave sequelae, the people influenced most severely by relocating are those who have lost their eyesight. In the past, patients who lost their eyesight could not work; they could not earn a living and fell into poverty. Loss of eyesight was considered one of three major causes of suffering in a patient’s life and the other two being notified of one’s diagnosis and getting a tracheotomy. In the past, blindness was considered the most serious of the sequelae and continues to be today. In relocating, blind patients must remake their mental map of their environment, but this is difficult because their memory abilities decrease with age.
\nSurvivors’ living environment can alleviate their multiple overlapping sequelae, but it takes time to adapt a new setting to one’s particular needs. This is most challenging for blind patients because changing their environment means they must make an entirely new mental map of their surroundings.
\nWe must now think about how we will care for the survivors until they all pass away. Relocating survivors to one facility may cut costs, but also robs survivors of the setting they have adapted to; this threatens non-maleficence. Survivors need individuals to advocate for their rights, especially as their decision-making abilities and power to acknowledge reality decrease from dementia, making it easy to threaten respect for autonomy. Thus, beneficence is more important now than ever in order to protect the weak.
\nOn the other hand, Japanese medical policy and the medical system must find ways to innovate. As the elderly population grows and the overall population shrinks, the current medical and medical finance systems cannot endure as they are; they must change. Although the law has guaranteed survivors a high quality of life, there may come a day when the nation becomes dissatisfied with shouldering the rising cost of supporting multiple sanatoria. We must seriously consider bringing all remaining patients to one site in order to improve cost-effectiveness.
\nThere is an ethical dilemma in the midst of these circumstances: confronting justice and/or equality, and beneficence and non-maleficence. Unfortunately, we do not yet have a solution. However, we must prevent the public from criticizing and be advocates for survivors. We must find a solution to help sanatoria coexist with society and prosper. If we cannot avoid bringing the remaining patients together at a single facility, we must find methods of decreasing the negative aspects of changing their living environment. We must help society understand the meaning and importance of where survivors live.
\nIn the section above, we discussed the difficulties of caring for the survivors until they all pass away. In this part, we talk about our efforts to support survivors by providing them with a high quality of life and caring for them until they die peacefully (with support from the Toyota Foundation Research Grant Program 2013). In addition, we discuss the bioethical implications of this practice.
\nAt this time, the background of our project is as follows [34]:
\nAging survivors’ deaths cause the community to reduce and collapse over time. There is a negative impact on survivors’ physical and mental health as the shrinking of their community causes them to feel helpless, hopeless, and lonely. It is a feeling comparable to the enforced isolation from their parents that many survivors experienced as children. We must consider how we can alleviate the survivors’ sense of loss and prevent growing negative physical, psychological, and social influences.
Many survivors do not have any family except for an elderly spouse, so sanatorium staff must care for survivors until they die, instead of their family.
Now is our last chance to record the experiences of aging survivors, but many do not have a means of expressing themselves. However, some survivors have produced literary or artistic works.
We will lose these storytellers when they pass away. We must consider how we will pass on their experiences.
As survivors do not have much time left, we looked for an immediate, effective method of working with them to preserve their experiences and communities. We chose life review. With this technique, we can subjectively construct a narrative of their life experiences. It is a process of reweaving one’s own life, supported by a good listener (in our case, supportive nurses in the sanatorium), promoting the rediscovery of the meanings in one’s life, conducting a reevaluation of life, and gaining a sense of self-consistency.
\nThe expected effects for survivors are as follows: (a) gaining a sense of self-expression through constructing their own narrative; (b) experiencing a cathartic effect, promoting reevaluation of their lives, and developing new meanings; and (c) having a positive effect on survivors by having nurses serve as supportive listeners. As survivors face their own impending deaths, they are acutely aware that the deaths of their comrades have resulted in a shrinking community, thus creating a crisis for survivors. The expected effects for nurses in the sanatorium are as follows: (a) it gives them a chance to exercise their ability to listen attentively and express empathy; (b) it deepens their understanding of the survivors and what they experienced; and (c) it gives them the opportunity to reevaluate their own roles, as well as a sense of responsibility and pride in caring for survivors. These are all nursing practice abilities that are required in end-of-life care. The expected effects for the relationship between survivors and nurses are: (a) a deepening of relationships on both sides and that nurses caring for survivors on their deathbeds will forge a deeper relationship with the patients. The larger point is that supporting survivors’ lives and caring for them until they pass away is a nurse’s most important duty in a sanatorium. Moreover, nursing practices directly influence survivors’ quality of life.
\nThe significance of creating a survivor’s life review is: (a) being able to publish the life review in a book, thus passing on survivors’ wisdom and experiences to the next generation, and directly contributing to increasing their dignity and satisfaction; (b) since survivors are aging and gradually passing away, this life review book will be the last record of these storytellers and is thus a valuable primary source; and (c) if we continue our qualitative and inductive analysis of these life reviews as raw data, we will find universal meanings in their experiences and will be able to explain their lives plainly and accurately via abstraction.
\nWe conducted life reviews with 17 survivors, with nurses as listeners, and published them in 2015. We included a portion of the life review of Mrs. Hanako Kadowaki at the beginning of this chapter [1]. These 17 life reviews are powerful and fascinating to read; they are useful for thinking about bioethics and about how society cares for people who suffer from discrimination. We can learn both negative history and wisdom from the Hansen’s disease survivors. We hope that students of medicine, nursing, pharmacy, and others in the medical field, those who work in Japan’s medical administration, and the general population (both young and old people) will read it and learn from it, so as to not allow the suffering of Hansen’s disease patients to be repeated in the future. Having worked on these life review projects in the sanatorium, the nurses now have increased self-confidence and pride in their jobs, and can provide even higher quality end-of-life care.
\nIn another part of our research, one of the survivors had been homeless and experienced the hardships of wandering as a pilgrim before entering a leprosarium. This survivor said, “I think my life had a checkered destiny, but I was not miserable. Now, my comrades and I know that the adversity we faced was nothing serious.” Thus, the survivor expressed catharsis. In the 17 life reviews we conducted, many survivors showed bitterness toward their past treatment and the policies under the Leprosy Prevention Law, but are now satisfied with and thankful for their current lives. The reasons for their satisfaction and gratitude are: (1) The nation officially apologized for their treatment and provided reparations. Specifically, the Prime Minister, the National Diet, the Minister of Health, Labor, and Welfare, and the Chief Justice of the Supreme Court all issued formal, official apologies. These apologies made the survivors feel relieved. (2) The survivors do not have economic problems, thanks to the new law that aims to resolve all remaining issues of Hansen’s disease in Japan. (3) Medical and welfare staff now provide survivors with ample care.
\nEnd-of-life care is based on nursing practices. In nursing, we must understand our patients based on holism, practice healthcare based on scientific problem solving, and provide human care based on philosophy. Holism [35] requires looking at the system as a whole, beyond the sum of its parts. We cannot understand the whole only by looking at each element alone; however, through reductionism, we can understand complex phenomena via fields such as biology. In nursing, we understand the notion of “being whole as a person” from Holism. Thus, we grasp at least three points of view and attempt to integrate our understanding. We view our subjects as physical, psychological, social, and spiritual beings. We approach them with consideration for their own life spans. We understand not only pathological and objective diseases, but also the subjective and phenomenological experience of illness. If we want to understand the current thinking and emotions of Hansen’s disease survivors, we must grasp their life histories; hence, our project is based on holism. The main characteristics of caring are reciprocity and mutual recognition. According to Jean Watson [36], the purpose of human caring is protecting, maintaining, and enhancing human dignity. In transpersonal caring, both nurses and patients share a spiritual dimension with each other. In other words, when we respect the patient as an irreplaceable, important person, then the nurse and patient can experience humane and affective interactions. If we have a caring mind, we cannot abuse the patient. Thus, caring prevents deviation from the four principles of bioethics. A peaceful death is an extension of daily care for survivors based on an understanding of them through holism and human caring, which is what our project is founded on.
\nJapan’s political leaders apologized to the survivors, but who heals the survivors’ suffering and embodies this apology? High quality daily care by medical and welfare staff in sanatoria directly influences survivors’ quality of life. Our project aims to enhance their quality of life and allows them to have a peaceful death. Our nursing practice embodies this national apology and the principles of bioethics.
\nAt present, Hansen’s disease is a progressive illness, and new patients live in developing countries. Patients often face discrimination. We must elucidate how stigma is born and adhere to the four bioethical principles in order to prevent discrimination.
We think there are three types of people who discriminate: a few support patients, a few persecute them, and the majority do not have correct knowledge of Hansen’s disease. If majority agree to persecute patients, they will suffer from greater discrimination. However, if majority support patients, then discrimination lessens. It is important to educate the public and promote awareness of Hansen’s disease. Since it is possible that the main people who discriminate have their own psychopathological problems, it is important for patients to understand the real causes of discrimination and how it operates in society, thus putting an end to their challenges and those of people who are prejudiced. There is a lot of bullying and harassment in general and among children. It is important to teach the public that Hansen’s disease is not a stigma.
The main source of discrimination against Hansen’s disease patients is not only based on unpleasant feelings due to the patients’ appearance, but also a fear of infection. In the future, should a pandemic of a lethal, drastic infection—such as Ebola hemorrhagic fever—break out, people may ostracize patients due to their fear. We must find ways of protecting against infection yet also avoid discrimination, based on what we have learned from the past negative treatment of Hansen’s disease patients.
Survivors’ experiences living with stigma not only results in suffering, but also wisdom. Like the life-affirming logo therapy that came from a survivor of Auschwitz, the insight gained from living through extreme situations will hearten other suffering individuals and suggest solutions to future problems.
In order to solve ethical dilemmas in caring for aging Hansen’s disease survivors, we must understand the pathological causes of their symptoms and how they influence daily life for survivors. A pathological understanding is important for solving the ethical dilemmas in treating any disease. When we make a judgment based on the principles of bioethics, we can avoid unnecessary discrimination.
In order to alleviate the hardship of oppressed persons, we need a daily nursing practice based on understanding subjects through holism and human caring, thus embodying the principles of bioethics.
This work was supported by JSPS KAKENHI Grant Number 15K15797.
\nAn injury that occurs in a quick manner, which often leaves the skin torn, cut, or punctured, or wherein the skin or any other tissues of the body undergoes acute trauma resulting in a contusion, is defined as a ‘wound’. This is when the body’s repair mechanism works to repair the damage by replacing the damaged tissue with newly synthesized tissue. This is characterized by a cascade of highly coordinated reactions that occur at the tissue damage region, working to restore normal tissue, which is called wound healing mechanism. This process requires nutrients and amino acids in adequate amounts to ensure the smooth repair of damaged cells, the supplementation of which has been viewed as a possible solution to augment the process and provide better strength and elasticity to the newly developing tissue [1].
It is known that collagen, being an integral part of most tissues in the body, plays an important role in the structural stability, elasticity, and tensile strength. It is therefore unsurprising that collagen is vital for restoring the structural integrity of the wounded tissue. It has been observed that, formation of scar tissue is an integral part of wound healing in most cases, with epidermal wounds being the exception. This scar tissue is composed primarily of collagen. This makes collagen synthesis an extremely crucial part of the wound healing process [2]. It is therefore practical to employ collagen supplements to augment and speed up the process of hound healing, and even enhance the tensile strength and other innate properties of the tissue. Through a study conducted by Felician et al., it was proven that collagen obtained from a species of jelly fish was indeed effective in escalating the pace of wound healing, making it a potential product that could be used in treating major wounds [3]. There is growing interest in the applications of collagen powder derived from marine sources to treat wounds effectively and reducing the possibility of a scar on the skin along with many other biomedical applications [4]. However, it must be understood that collagen powder is not the only form of collagen supplement for treatment of wounds and other tissue replacement procedures. There are a variety of forms, in which collagen is used as a biomaterial, for wound treatment [5].
Collagen derived from various sources is fabricated into various scaffolds, which can be implanted or grafted into the region of tissue damage, to act as an effective substrate for the attachment of precursor cells and allow their proliferation, thereby increasing the chances of tissue repair effectively. These precursor cells are multipotent adult stem cells which have the ability to differentiate to form various cells depending on the environment they are in, or the stimuli they receive for differentiation. These scaffolds can also be in the form of hydrogels, or fibers, and not just solid in nature. The use of collagen has proven to be effective for wound healing, due to the fact that it is an integral part of the extracellular matrix (ECM) on which most tissues are constructed [6]. Nanotechnology is a field of science that has been explored for its possible applications in the biomedical sector. Many nanomaterials such as nanoparticles and fibers are known to possess antimicrobial activities, which could be effective in the wound healing mechanism for the prevention of further infection. It is thereby prudent that the nanomaterials should be tried and tested along with those of collagen in order to come up with innovative methods to treat major wounds effectively. This chapter aims to summarize the importance of collagen and nanoparticles, synthesis of nano collagen in order to benefit from the wound healing properties of both nanoparticles and collagen, along with the areas of wound healing in which nano collagen is currently being used.
Nanotechnology is the branch of science and engineering that involves design, construction, and characterization of materials by restructuring the atoms and molecules with the size range of 1–100 nm in one or more dimensions [7, 8]. The engineered materials are nanomaterials that show distinct chemical and physical properties compared to the bulk materials due to the synthesis and assembly at the molecular level that can be exploited for commercial use [9]. Nanomaterials can be of different shapes mainly based on their dimensions i.e., nanoparticles of zero dimension, nanorods of one dimension, and nanosheets of two dimensions [10]. Nanoparticles, due to their small size have the ability to penetrate the bacterial cell wall, and though the cells metabolic pathway cause changes to the cell structure and function. Nanoparticles are also known to interact various components of the bacterial cell, such as lysosomes, enzymes, and ribosomes, thereby leading to oxidative stress, altered permeability of the cell membrane, protein deactivation, and altered gene expression, eventually causing cell death among the bacteria. Thus, it can be said that the Nanoparticles have antibacterial properties, which can be exploited for sterilization of larger wounds, thereby preventing infections from occurring during the wound healing process. When compared to the conventional wound healing drugs certain nanoparticles exhibit greater penetration of cell membrane [9]. Nanoparticles, nanocomposites, coatings, and scaffolds are the main nanomaterials used for wound healing (as shown in Figure 1). Nanoparticles can be (i) inorganic metal or non-metal (ii) organic non-polymeric or polymeric. Nanocomposites are made of porous materials, colloids, copolymers, or gels. Coating and scaffolds include hydrogels, nanofibers, films, and coatings [11]. Different classes of nanoparticles are involved for the treatment of wounds. They are discussed below:
Types of nanomaterials used for treatment of wounds. The figure is reproduced with permission from [
The antimicrobial property of metallic nanoparticles is exploited in wound management and can be used as a nanocarrier. The surface area to volume ratio of metallic nanoparticles is high. The small size enables them to cross barriers and penetrate the underlying layers of thick tissues like skin. These features make them ideal for drug delivery and to treat wounds. Some of the widely used metallic nanoparticles includes—silver nanoparticles (Ag NPs), gold nanoparticles (AuNPs), zinc oxide nanoparticles (ZnO NPs), iron oxide nanoparticles (IONPs), and titanium dioxide nanoparticles (TiO2 NPs) [12].
Polymeric nanoparticles include polymer nanospheres and polymer nano capsules. Biologically active molecules such as drugs, genes, and fluorophores are absorbed on the surface of polymer nanospheres forming antibiotic incorporated nanoparticles (NPs). Griseofluvin (GF), one such NP, is known to function as an effective carrier of biologically active entities [12, 13]. The polymer nano capsules are vesicles where the core contains bioactive agents surrounded by polymeric shell. The polymers used in the preparation can be natural polymers like starch, polypeptides, albumin, sodium alginate, chitin, cellulose, gelatin, polyhydroxy alkanoates (PHAs) or artificial polymers like polyethylene glycol (PEG), poly lactic acid co-glycolic acid (PLGA), polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), polyethylene etc. They show higher encapsulation efficiency and high stability of encapsulated active substance that helps them in the effective delivery of drugs to targeted sites [13].
Nano emulsions shows small droplet size and high surface area that makes them a suitable vehicle for drug delivery to treat wounds. A unique feature of these nano emulsions is their ability to deliver hydrophobic drugs [14]. They also have long shelf life, and are easily formulated [12]. The components of nano emulsions include different oil types, emulsifying agents like sodium deoxycholate, sodium dodecyl sulphate, antioxidants, chelating agents, preservatives etc. [15].
Solid-lipid nanoparticles are used as drug vehicles in case of inflamed or damaged skin. They are efficient and non-toxic carriers of both lipophilic and hydrophilic drugs. The structure is made up of long-fatty acid chains of palmitic acid, stearic acid or arachidic acid taurocholate, emulsifiers, and water.
Nanofiber scaffolds/mats, considered as a substitute to damaged ECM, are mainly used in the wound dressing due to its healing power and unique structure. As the scaffolds are applied on the wound there will be attachment of fibroblasts and formation of matrix that acts as ground substrate and aid in faster wound recovery. Manufacturing of nanofibrous scaffolds involves electrospinning that produces uniform nanofibers [16].
Hydrogels are used as delivery vehicles for wound treatment due to their properties such as high porosity which keeps the wound environment moist, and the presence of 3D polymeric matrix that absorbs the wound exudates allowing for proper permeation of oxygen [12]. While nanogels demonstrates some advanced features compared to those of hydrogels such as stability, ease of synthesis, quick response to stimulus, an adjustable size that can be exploited for drug delivery, controlled release of drugs, and tumor imaging. Nanogels are made up of chemical polymers and biomolecules. The nanogels of amino acids and polypeptides are easy to synthesize and modify and show higher biocompatibility [17].
The word ‘collagen’ is derived from a Greek term ‘kolla’, which means ‘Glue’. Collagen is essentially a matrix, which holds the connective tissue together, making it a major component of the ECM, and connective tissues, and is rightfully called the most abundant protein in the animal kingdom [18]. Collagen is a major component of the ECM, which provides mechanical support for cell growth and their integrity. Collagen represents an entire superfamily of glycoproteins, having, a polypeptide sequence signature with [Gly-X-Y]n as the repeating amino acid unit, wherein X and Y are proline and hydroxyproline respectively. Another salient feature of these glycoproteins is their noteworthy quaternary structure with the right-handed triple helix structure composed of three left-handed polyproline chains of uniform length. The chains in the triple helix can either be identical, forming homotrimers as seen in collagen II, or be different from each other, forming heterotrimers, as seen in collagen IX. Presence of glycine is invariant in collagen and is known to stabilize the collagen structure. It has been found that the absence of glycine or any mutations to the same is known to cause disruption in the hydrogen bonds formed in collagen and distort the structure [19].
The presence of collagen and collagenous structures throughout the animal kingdom indicates its importance in biological structures. Collagen is expressed in all life forms classified under the animal kingdom. Right from sponges, the simplest multicellular animal which expresses genes for the formation of at least two types of collagens, to the various vertebrates, in which collagen is a major component of various connective tissues, thereby accounting for roughly a quarter of the whole-body protein in humans [20]. The basic triple helical pattern has been partially carried over into the architectures of other complex molecules in higher organisms, with complex physiologies. Evolutionary branching which was partially driven by chromosomal duplication has resulted in a plethora of collagen types, which are genetically distinct. There are 29 types of collagens that have been identified so far [21]. Although the exact function of many types of collagens is yet to be confirmed, the role and presence of collagen throughout the body is unmistakable. However, it is known that collagen types I, II and III represent the majority (approx. 80–90%) of the total body collagen. They are known to provide mechanical and tensile strength to the skin and various other organs. The ability of fully developed collagen to integrate hydroxyapatites and undergo mineralization to amalgamate with solid structures such as bones and teeth, combined with its nature of elasticity and strength makes it a very desirable candidate to be used as a primary component of biomaterials with various applications [22]. Biomaterials are defined as synthetic components that may be transplanted into body tissue as a part of a medical device. Biomaterials can also be employed to replace an organ or a part of it, thereby aiding it in its physiological and mechanical functions [23].
Despite the wide range in the types of collagens, only a handful of them are actually utilized for the production of collagen-based biomaterials. Fibril forming collagens, such as type I, which also happens to be the most abundant collagen in mammals, is often employed for construction of collagen-based biomaterials for various purposes such as wound healing and tissue engineering, and even 3D bioprinting of collagen-based structures or scaffolds [24]. Collagen can be extracted from any animal’s tissue including vertebrate’s skin and tendons, porcine skin, gut, bladder mucosa, rat tails, as well as invertebrates’ sponges and corals. The extracted collagen can show a slight difference in some characteristics, depending on the source of the animal, and the tissue. It has been found that the use of collagen from marine sources [25, 26, 27, 28] has advantages over those obtained from terrestrial organisms, such as being environmentally sustainable, high production of collagen, non-toxicity, and ease of absorption thanks to its lower molecular weight. However, occurrence of allergies and transmission of disease can hamper the use of collagen obtained from animal sources, thereby the application of recombination technology was duly suggested, wherein yeast and
Biomedicine is currently seeing an increase in the use and integration of collagen-based scaffold and biomaterials in its applications. The technology aids the creation of biomaterials which exhibit biomimicry of the complex native tissues and organs. Decellularized collagen and refined scaffolds are the two categories into which collagen-based biomaterials are categorized. While the decellularized collagen structures retain most of the structural and functional properties of the tissue from which it is derived from, refined scaffolds are mostly obtained from the purification and polymerization of collagen. Decellularized collagen exhibits biomimicry the best [30]. Tissue grafts for tissue engineering, self-assembled hydrogels, freeze dried sponges, collagen films and tubes are some commonly used collagen-based biomaterials.
Tissue grafts are one of the most commonly used collagen scaffolds. Due to their resemblance to the native tissues, along with the ability to promote cell attachment and spatiotemporal organization of the cells, tissue grafts have been demonstrated as the most convenient and effective implantable devices [31]. Self-assembled hydrogels are generally used in the form of cell carriers, and injectables. They are often reliable for soft tissue treatment, for they resemble the structures on polymerization to form a fibrillar hydrogel structure, which is held together by ionic and hydrophobic bonds, thus aiding the entrapment of fluids, making it conducive for the exchange of ions and metabolites in the environment created [32]. Collagen type I hydrogels in combination with the appropriate precursor cells have been extensively used for the repair and as a structural and mechanical support for the attachment and stable growth of tissues such as skin to treat burns [33], cardiac myocytes [34], neurons [35], ocular tissues [36], etc. Collagen type I and type II hydrogels have often been used in combination for the treatment and repair of osteochondral tissues, and cartilage [37, 38]. Collagen scaffolds that can be easily used as grafts for various clinical purposes are created by the freeze-drying technique, wherein, collagen on undergoing freezing in a controlled environment, is trapped within the ice crystals formed, and is porous enough to facilitate cell migration, attachment, and growth [39]. So far, a variety of cell populations have been used to improve the bioactivity of the collagen sponge, and the experiments performed have shown encouraging results both
Nano collagen is the term used to describe collagen brought down to the nanoscale range. This substance has the desirable properties of both nanoparticles, such as a high ratio between the surface to volume of the particle, and collagen, with its wound healing properties of biomaterials, and their functions simultaneously. The downscaling of the size of the collagen fibers, is beneficial in terms of the penetration, and wound accessibility to initiate wound healing [44]. Nano collagen is produced through various chemical, physical, and self-assembly methods, such as emulsification, complex coacervation, phase separation, nano spray drying, desolvation and many other techniques. The following section explains briefly the most popular techniques employed. Nano collagen fibers are produced through the following techniques: (a) electrospinning (b) nano emulsion (c) electrospray deposition (d) milling (as shown in Figure 2, Table 1).
(A) Electrospraying—after applying a high voltage to the protein solution, a liquid jet stream is released via a nozzle (coaxial needle), generating an aerosolized droplet. To ensure that the polymer solution comes out of the syringe as NP, a high voltage is provided to it. (B) Electrospinning—at a high voltage and low current in the spinneret, collagen polymer solution added dropwise. The Taylor cone is formed at such conditions. The columbic forces also cause the dehydration of the ejected polymer thereby resulting in thin and dry fibers of nano collagen. (C) Milling—the application of mechanical energy through the spinning of a milling bowl breaks down a polymer substance into finer NPs. Milling balls are used to conduct high-energy mechanical impacts to break down polymers utilizing centrifugal force. (D) Nanoemulsion—the emulsion is formed by the mechanical agitation of two immiscible liquid phases, one of which has the protein, and the other in which the drug is dissolved. Figures A, C, and D are reproduced with permission from [
Preparation method | Principle | Advantage | Limitation | References |
---|---|---|---|---|
Electrospraying | Uses electrostatic field to create nano collagen fibers from a polymeric solution of collagen | Can be upscaled for industrial purposes; ease of particle synthesis due to single step process; formation of dry particles | Reduced flow; can degrade some macromolecules | [46] |
Electrospinning | Uses a high voltage difference to generate dispersible nanoparticles from collagen solute | Can produce fine fibers of collagen; Emulates ECM closely; cost effective | Time consuming | [47] |
Milling | Uses mechanical energy to break down a polymeric material of collagen to nanoparticle sizes | Economical; easy experimentation; controllable nanoparticle size | Chamber has to be cooled due to heat release; cannot control nanoparticle shape | [48] |
Nanoemulsion | Uses mechanical agitation to form nanoemulsions by the combination of two immiscible liquids in different phases. | Simple process; easy recovery; high flexibility and selectivity | Requires appropriate surfactant due to unstable thermodynamic nature; the organic solvent needs to be removed, for the residues may be toxic | [49, 50] |
Collagen nanoparticle preparation methods, their principles, advantages and limitations.
Electrospinning is one of the methods used to create nano collagen fibers, wherein nanofibers are created from polymeric solutions in the presence of an electrostatic field. Electrospinning is achieved by charging a spinneret to high voltages and low current, and then adding droplets of the polymeric solution. As a result, the surface becomes highly charged, and elongates to form a conical shape, which is called the Taylor cone. The conical form is a result of the electrostatic repulsion between the charged droplet surface and columbic forces from the spinneret. At a specific threshold of the electric field, the electrostatic forces are strong enough to overcome the surface tension holding the Taylor cone, thus creating the fibers by stretching the cone, whipping it. This process is generally preferred to create nano fibers, because it is cost effective, and can produce nano collagen scaffolds for various purposes including tissues engineering, tissue repair and regeneration [47], and matrices that mimic the native ECM. The fibers produced through electrospinning are dry, and devoid of any solvent molecules, which are then collected in a metallic collector, which also determines the shape [51]. Over a period of time, electrospun collagen nanofibers have been endowed with certain ‘smart’ abilities, to improve their applications. Some smart abilities include response to external stimuli such as change in pH, exposure to light, and magnetic fields, etc., retaining a shape memory, self-cleaning, and some more [46].
As the name suggests, electrospray deposition is a process which involves the spraying of nano collagen solution as a fine mist onto a specific target. This method is mostly used for the applications of nanoparticles in the biomedical field for pharmaceutical application. This is mostly because, in this technique, collagen is used in its particle form. It is then sprayed through a nozzle onto a target with a high negative voltage, in the form of a fine mist. The solvent of the collagen particles generally evaporates on deposition onto the target surface, leaving an even spread of nano collagen particles, making it ideal for drug delivery purposes. This evaporation prevents the aggregation of molecules, and thus reduces the risk of contamination [52].
Milling is a process in which nano collagen is produced by the application of great amounts of mechanical stress onto a polymeric solution of collagen, to form particles of the nano scale range. This process is one of the most inexpensive methods for the large-scale production of nano collagen [53]. The mechanical energy along with the kinetic energy in the milling container also produces large amounts of heat, which can lead to the denaturation of collagen [54]. Therefore, this generation of heat is contained by performing this process at cryogenic temperatures, with the use of liquid nitrogen, thereby preserving the integrity of collagen.
Nanoemulsion is a method used to integrate collagen with nanoparticles in a droplet form. Two immiscible liquids in different phases, i.e., oil-in-water-phase (oil is dispersed in water) and water-in-oil phase (water is dispersed in oil) when combined, form a concoction called an emulsion. Nanoemulsions differ from emulsions in their size ranges. The size of a nanoemulsion droplet ranges from 20 to 200 nm, while a normal emulsion droplet size is around 1 μm [55]. An aqueous phase with collagen, and a hydrophilic surfactant in water, is mixed with an organic phase with a lipophilic surfactant in a solvent that is immiscible in water and is continuously agitated under room temperature conditions to produce a uniform emulsion system. Nano collagen emulsion particles are then obtained by combining this emulsion system with a heated oil in a drop-by-drop manner [56]. Nanoemulsions naturally tend to penetrate deep into the tissue to deposit active compounds. This property has been exploited for purposes such as drug delivery in pharmaceutical, food and cosmetic industries. The same properties can be attributed to the collagen Nanoemulsion droplets to enhance the wound healing mechanism and speed up the process. The production of collagen nanoemulsions has increased greatly along with their application mainly in the field of cosmetics and drug delivery due to the technological advantages it offers for the manufacturers [57].
Collagen is a major component of the bone matrix. Bone formation is facilitated by the osteoblasts, which are involved in the production of collagen type I protein. The ECM supports the collagen fibers (50–500 nm) synthesized by the osteoblasts. The hydroxyapatite crystals are then deposited on these collagen fibers, leading to the hardening and maturation of the bone [58]. This mechanism can be exploited for the purposes of bone remodeling, in the case of a grave bone injury such as a compound fracture. A collagen scaffold can be grafted onto the damaged tissue area, to provide a solid support onto which the apatite crystals can be deposited, to increase the speed and efficiency of new bone formation. It is thus prudent that the collagen scaffold mimics native collagen fibers to achieve successful bone grafting and promote optimal bone regrowth.
It is well known that bone related tissue trauma is difficult to treat and is a time-consuming process, due to the complexity of the bone healing process itself, and the loss of bone from non-sterile wounds, creating a high risk and susceptibility for infections. Cardoso et al., proposed the use of silver nanoparticles stabilized with type I collagen to form nano collagen biomaterials (AgNPcol) for the collagen scaffold to support rapid bone remodeling. This was an optimal solution for the problem of infections caused due to the non-sterility of the bone wounds. The silver nanoparticles in the collagen also showed anti-microbial activity against a number of microorganisms. Thereby proving to be effective in wound healing. The developed cells also showed no signs of cell toxicity [59]. In another study by Sun et al., collagen scaffolds were infused with AgNPs along with BMP2, a bone morphogenic protein to improve the bone healing process effectively. The role of silver nanoparticles in antibacterial property was already established. However, the incorporation of the bone morphogenic protein induced an increase in the expression of runt related transcription factor 2, osteopontin and osteonectin, which are known to accelerate the differentiation of the bone marrow derived mesenchymal stromal cells, thereby proving the therapeutic potential of nano collagen in bone grafting, and healing [60].
Poor development of alveolar ridge after tooth extraction is an issue faced by most dental patients due to the lack of oral hygiene or knowledge about it. Wang et al., in their research, proposed the usage of artificial nano collagen bone implants. This was done to support the alveolar ridge post extraction of tooth. The implantation was followed by a CT scan to track the bone mineral density progressively. It was found that the implanted nano collagen bone has successfully fused with the native alveolar bridge. It also showed an increase in the overall bone mineral density [61].
Treatment of damaged nerve tissues has been a topic of interest for many researchers. This can be attributed to the inability of terminally differentiated neurons to undergo further cell division and also the fact that the nervous system controls and coordinates most of our body’s processes. Damage or injury caused to the nerve tissue can seriously impair many functions of the body. Autografts of the nerve tissue has been performed in some cases. However, this has proven to be more challenging, due to the shortage of the donor sites, or occurrence of deformities. This has fuelled the search for alternative methods or materials to treat nerve damages effectively. The extensive study on collagen and nano collagen has tested the ability of collagen to act as an effective scaffold and promote cell attachment and growth [62]. Collagen has been used in the manufacture of nerve guidance conduits to aid the nerve regeneration in small nerve gaps of 2–3 cm across the peripheral nerve tissue. The use of collagen hydrogels for the treatment of lesions in the central nervous system effectively has been demonstrated by Orive et al. [63]. Further degradation of the nerve tissues can be prevented on injection of collagen nanospheres, which have the potential to deliver therapeutic drugs, and other stem cells for structural support as well [64]. Zhang et al., illustrated the application of collagen—nano size β tricalcium phosphate, together with growth factors of nerves and some collagen fibers, for the treatment of facial nerve repair and regeneration. Improved action potential was seen in the muscles, along with the formation of thicker myelin sheath, making it a highly promising avenue for further innovation and studies in nerve regeneration [65].
Articular cartilage covers the edge of a bone, and it is a connective tissue which forms a synovial joint that provides low frictional surface and enables the smooth movement of the joint. So, any damage to the articular cartilage results in acute pain during the movement of the joint. However, unlike most tissues in the body, articular cartilage lacks the potential to heal itself by replacing damaged areas in the tissue with new cells. This is mainly due to its avascular nature, i.e., there is no direct blood supply to the cartilage, thereby making it a difficult to heal by targeting therapeutic drugs. Treatment for articular cartilage necessitates surgical intervention techniques such as chondrocytes implantation and osteochondral transplant. However, the high cost and numerous other risk factors of patients has given rise to much needed research in the field of cartilage tissue engineering [66].
Cartilage tissue engineering employs the use of 3D bioprinting for the creation of collagen 3D scaffolds, which are then treated
The process of wound healing involves four steps viz., hemostasis, inflammation, proliferation, and remodeling which occur in a sequential order [69]. Disruption of any of these steps will make the process lengthy. The main issue involved in wound healing is infection by pathogens that results in inflammation, interrupting the healing process [45]. Schimek et al., developed full-thickness skin equivalents (ftSEs) to hold the 96-well cell culture [70]. Collagen powder can be used as the dermal substitute as they are part of the ECM that shows slow biodegradation and accelerates wound healing [45]. Collagen with nanoparticles is widely used in therapy. Munish et al., used collagen granules for the diabetic foot ulcer treatment and the results were compared with the saline dressing. The study demonstrated that the wound, when treated with collagen showed a speedy recovery [71]. In another study, Akturk et al., developed gold nanoparticles (AuNPs) based collagen scaffold, and they were incorporated into the cross- linked collagen scaffolds. It was found that it helps in enhancing the stability against enzymatic degradation and increases the tensile strength [72]. The main advantage includes the absence of rejection and the fact that they can reduce the inflammation in and around the wound. Apart from gold nanoparticles, the use of silver as an antimicrobial agent has also been of great interest recently. Silver nanoparticles (AgNPs) are usually used in the treatment of burns and infection as they are known to demonstrate antibacterial property. There is sufficient evidence to prove that the bacterial resistance against AgNPs may not be a matter of concern, for AgNPs are known to hinder quorum sensing mechanisms in bacteria [45].
Collagen-based dermal scaffolds are coated with silver nanoparticles that act as antimicrobial dressing without having any toxic side effects. Nano silver reacts with gram-negative and gram-positive bacteria, causing damage to the intracellular structure. The positively charged silver nanoparticles react with negatively charged bacterial surfaces leading to the disruption of the inner membrane. During electrospinning, the synthesized silver nano particles are incorporated into the collagen nano fibers. The
Collagen nanoparticles have shown promise as treatment carriers [73]. The recent trends in nanotechnology research and development aims to create collagen scaffolds that deliver the drug to the specific site and are released in a controlled manner [74]. Gold nanoparticles with different concentrations of gold (Au) was synthesized and coated onto collagen to form an amalgamation of nanoparticles and collagen (Au-Hp-Col). This amalgamation was found to be effective in the delivery of the drug Doxorubicin [70]. Poloxamer 407 (PM) is a polymer soluble in water used in the delivery of ophthalmic drugs like Ketorolac Tromethamine (KT). The PM is incorporated into the cellulose nano collagen particles that showed controlled release of the drug
Cardiovascular disease is the major cause of death worldwide [77]. These disorders are caused by reduced blood flow by blockage of blood vessels [78, 79]. Presently, the saphenous vein, the internal thoracic artery, and autologous vessels are used as grafts which are known to perform better than the synthetic alternative [80]. However, their limited availability and invasive harvest make them unsuitable for use. Tissue-engineered vascular grafts (TEVG) are currently used in order to overcome these limitations [48]. TEVG makes use of modern technology for the construction of vascular medical implants. The collagen along with the other components are used as a scaffold in the preparation of the TEVGs. In a previous study, Park et al., described a poly-epsilon-caprolactone (PCL) vascular graft, and its suitability for healing process. It was observed that the graft undergoes gradual degradation replaced by natural blood vessels. Collagen is also incorporated on to the inner layer and silica (sol-gel-derived ceramic) into the outer layer of PCL to improve the vascular response [49].
This chapter conclusively describes the importance and role of nanoparticles-based collagen biomaterials in the treatment of various wounds. The ECM is mainly comprised of collagen, which provides support and elasticity against mechanical stress. While collagen in itself is useful in the form of various biomaterials like scaffold s and hydrogels, the introduction of nanotechnology to it comes with its own set of challenges as well as advantages. The reduction of collagen to the nano particle’s sizes, giving it a large surface-to-volume ratio, is known to increase its efficiency of dealing with mechanical stress, thereby making it a viable option for treatment of wounds. Multiple research studies are conducted on wound healing using various materials and methods to reduce risk infection and aid in speedy recovery of the patient. The antimicrobial properties of nanoparticles of various elements such as gold and silver has already been proven, which can be further exploited in the effective treatment of wounds and injuries, in combination with collagen. The current challenge lies in the effective incorporation of nanoparticles and collagen in the production of nano collagen biomaterials, upscaling the production of nano collagen and making it affordable to the general public.
NM thank Global Innovation and Technology Alliance (GITA), Department of Science and Technology (DST), India [Project Number-GITA/DST/TWN/P-95/2021], and Indian Council of Medical Research (ICMR), (Project Number-ITR/Ad-hoc/43/2020-21, ID No. 2020-3286) Government of India, India for financial support.
The authors declare no conflict of interest.
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The presence of multidrug-resistance with a wide range of extracellular enterotoxin genes, virulence factors, and Panton-Valentine leukocidin (pvl) cytotoxin genes confer life-threatening traits on MRSA and makes them highly pathogenic and difficult to treat. Clonal complex 398 (CC398), a predominant clonal lineage of livestock-associated-MRSA in domestic animals and retail meat, is capable of infecting humans. In order to monitor and prevent MRSA contamination, it is critical to understand its source and transmission dynamics. In this review, we describe MRSA in food-producing animals (pig, cattle, chicken), horses, pet animals (dogs, cats), and food products (pork, beef, chicken, milk, and fish).",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Jungwhan Chon, Kidon Sung and Saeed Khan",authors:[{id:"189634",title:"Dr.",name:"Kidon",middleName:null,surname:"Sung",slug:"kidon-sung",fullName:"Kidon Sung"},{id:"190400",title:"Dr.",name:"Jungwhan",middleName:null,surname:"Chon",slug:"jungwhan-chon",fullName:"Jungwhan Chon"},{id:"190401",title:"Dr.",name:"Saeed",middleName:null,surname:"Khan",slug:"saeed-khan",fullName:"Saeed Khan"}]},{id:"52755",doi:"10.5772/65978",title:"Bee Products and Essential Oils as Alternative Agents for Treatment of Infections Caused by S. aureus",slug:"bee-products-and-essential-oils-as-alternative-agents-for-treatment-of-infections-caused-by-s-aureus",totalDownloads:1908,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"Bacteria of the genus Staphylococcus are important human and veterinary pathogens. A crucial characteristic for this group of bacteria is that they can easily acquire mechanisms of antibiotic resistance for a plethora of antibiotics currently in use for human and animal therapies. Therefore, there is a great need to find novel, non-antibiotic chemotherapeutics with marked antistaphylococcal activity. Promising but still underestimated group of potential antistaphylococcal chemotherapeutics constitute bee products: honey, pollen, royal jelly, fermented pollen and especially propolis. Another group of natural products that exhibit promising antibacterial activity is essential oils. Usefulness of bee products and essential oils in the treatment of infections caused by S. aureus has been confirmed by results of many investigations carried out by researches in different regions of the world. In this chapter, we have presented the review of publication in this area as well as perspectives and limitations of future applications of these two groups of natural products.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Piotr Szweda and Barbara Kot",authors:[{id:"117528",title:"Dr.",name:"Szweda",middleName:null,surname:"Piotr",slug:"szweda-piotr",fullName:"Szweda Piotr"},{id:"189685",title:"Associate Prof.",name:"Barbara",middleName:null,surname:"Kot",slug:"barbara-kot",fullName:"Barbara Kot"},{id:"195004",title:"Dr.",name:"Barbara",middleName:null,surname:"Kot",slug:"barbara-kot",fullName:"Barbara Kot"}]},{id:"52875",doi:"10.5772/65761",title:"Bacteriophage Therapy: An Alternative for the Treatment of Staphylococcus aureus Infections in Animals and Animal Models",slug:"bacteriophage-therapy-an-alternative-for-the-treatment-of-staphylococcus-aureus-infections-in-animal",totalDownloads:1975,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"Staphylococcus aureus causes hospital-acquired (HA), community-acquired (CA) and companion animal and livestock-associated (LA) infections. Molecular epidemiology studies suggest that although host specificity may be associated with specific genetic lineages, recent human-to-animal and animal-to-human transmissions related to mobile genetic elements have been described. Gene transfers include virulence and antibiotic resistance genes, thus making it difficult to control multidrug resistance S. aureus infections. Bacteriophages (phages) and endolysins, the enzymes responsible for bacterial lysis by phages, are alternatives to the use of antibiotics for the control of S. aureus infections. In this work, we review current advances in the development of phage therapy and the study and design of recombinant endolysins to treat S. aureus infections. Preliminary results of bacteriophage isolation based on molecular epidemiology knowledge show that bacteriophages are specific of genetic lineages and that this strategy may be used as an approach to isolate and evaluate new bacteriophages for therapy.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Claudia I. Barrera-Rivas, Norma A. Valle-Hurtado, Graciela M.\nGonzález-Lugo, Víctor M. Baizabal-Aguirre, Alejandro Bravo-Patiño,\nMarcos Cajero-Juárez and Juan J. Valdez-Alarcón",authors:[{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",slug:"juan-jose-valdez-alarcon",fullName:"Juan José Valdez-Alarcón"},{id:"195005",title:"Mrs.",name:"Claudia Ibeth",middleName:null,surname:"Barrera-Rivas",slug:"claudia-ibeth-barrera-rivas",fullName:"Claudia Ibeth Barrera-Rivas"},{id:"195006",title:"MSc.",name:"Norma Anahí",middleName:null,surname:"Valle-Hurtado",slug:"norma-anahi-valle-hurtado",fullName:"Norma Anahí Valle-Hurtado"},{id:"195007",title:"MSc.",name:"Graciela M.",middleName:null,surname:"González-Lugo",slug:"graciela-m.-gonzalez-lugo",fullName:"Graciela M. González-Lugo"},{id:"195008",title:"Dr.",name:"Víctor Manuel",middleName:null,surname:"Baizabal-Aguirre",slug:"victor-manuel-baizabal-aguirre",fullName:"Víctor Manuel Baizabal-Aguirre"},{id:"195009",title:"Dr.",name:"Alejandro",middleName:null,surname:"Bravo-Patiño",slug:"alejandro-bravo-patino",fullName:"Alejandro Bravo-Patiño"},{id:"195010",title:"Dr.",name:"Marcos",middleName:null,surname:"Cajero-Juárez",slug:"marcos-cajero-juarez",fullName:"Marcos Cajero-Juárez"}]},{id:"53377",doi:"10.5772/66225",title:"Staphylococcus aureus Bacteremia in Adults",slug:"staphylococcus-aureus-bacteremia-in-adults",totalDownloads:2058,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Staphylococcus aureus is an important cause of bacteremia, and S. aureus bacteremia constitutes a serious condition with high morbidity and mortality, secondary to multiple complications including infective endocarditis and embolization. The incidence of bacteremia with S. aureus is increasing with more frequent use of medications that lower immune system response, and with the utilization of more invasive medical procedures. In addition, the emergence of resistant S. aureus isolates is becoming more common and can negatively affect the outcome of an individual if not diagnosed and managed properly. Health care workers encounter S. aureus bloodstream infections on a routine basis, and in certain situations, it becomes a very challenging infection to control. Because of the impact this entity has on health care costs and the increased use of resources, it is necessary to highlight the causes, clinical presentation, associated complications, and treatment measures. In this chapter, we will cover each of these points, with somewhat more emphasis on methicillin‐resistant S. aureus that is prevalent in both community and hospital settings and is more commonly associated with worsening prognosis and higher mortality.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Dima Youssef and Kate Molony",authors:[{id:"190397",title:"Dr.",name:"Dima",middleName:null,surname:"Youssef",slug:"dima-youssef",fullName:"Dima Youssef"},{id:"195814",title:"Dr.",name:"Kate",middleName:null,surname:"Molony",slug:"kate-molony",fullName:"Kate Molony"}]}],mostDownloadedChaptersLast30Days:[{id:"54154",title:"Staphylococcus aureus: Overview of Bacteriology, Clinical Diseases, Epidemiology, Antibiotic Resistance and Therapeutic Approach",slug:"staphylococcus-aureus-overview-of-bacteriology-clinical-diseases-epidemiology-antibiotic-resistance-",totalDownloads:7082,totalCrossrefCites:13,totalDimensionsCites:25,abstract:"Staphylococcus aureus is an important human pathogen that causes wide range of infectious conditions both in nosocomial and community settings. The Gram-positive pathogen is armed with battery of virulence factors that facilitate to establish infections in the hosts. The organism is well known for its ability to acquire resistance to various antibiotic classes. The emergence and spread of methicillin-resistant S. aureus (MRSA) strains which are often multi-drug resistant in hospitals and subsequently in community resulted in significant mortality and morbidity. The epidemiology of MRSA has been evolving since its initial outbreak which necessitates a comprehensive medical approach to tackle this pathogen. Vancomycin has been the drug of choice for years but its utility was challenged by the emergence of resistance. In the last 10 years or so, newer anti-MRSA antibiotics were approved for clinical use. However, being notorious for developing antibiotic resistance, there is a continuous need for exploring novel anti-MRSA agents from various sources including plants and evaluation of non-antibiotic approaches.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Arumugam Gnanamani, Periasamy Hariharan and Maneesh Paul-\nSatyaseela",authors:[{id:"192829",title:"Dr.",name:"Arumugam",middleName:null,surname:"Gnanamani",slug:"arumugam-gnanamani",fullName:"Arumugam Gnanamani"},{id:"204388",title:"Dr.",name:"Periasamy",middleName:null,surname:"Hariharan",slug:"periasamy-hariharan",fullName:"Periasamy Hariharan"},{id:"204389",title:"Dr.",name:"Maneesh",middleName:null,surname:"Paul-Satyaseela",slug:"maneesh-paul-satyaseela",fullName:"Maneesh Paul-Satyaseela"}]},{id:"53377",title:"Staphylococcus aureus Bacteremia in Adults",slug:"staphylococcus-aureus-bacteremia-in-adults",totalDownloads:2064,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Staphylococcus aureus is an important cause of bacteremia, and S. aureus bacteremia constitutes a serious condition with high morbidity and mortality, secondary to multiple complications including infective endocarditis and embolization. The incidence of bacteremia with S. aureus is increasing with more frequent use of medications that lower immune system response, and with the utilization of more invasive medical procedures. In addition, the emergence of resistant S. aureus isolates is becoming more common and can negatively affect the outcome of an individual if not diagnosed and managed properly. Health care workers encounter S. aureus bloodstream infections on a routine basis, and in certain situations, it becomes a very challenging infection to control. Because of the impact this entity has on health care costs and the increased use of resources, it is necessary to highlight the causes, clinical presentation, associated complications, and treatment measures. In this chapter, we will cover each of these points, with somewhat more emphasis on methicillin‐resistant S. aureus that is prevalent in both community and hospital settings and is more commonly associated with worsening prognosis and higher mortality.",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Dima Youssef and Kate Molony",authors:[{id:"190397",title:"Dr.",name:"Dima",middleName:null,surname:"Youssef",slug:"dima-youssef",fullName:"Dima Youssef"},{id:"195814",title:"Dr.",name:"Kate",middleName:null,surname:"Molony",slug:"kate-molony",fullName:"Kate Molony"}]},{id:"55253",title:"Clostridium difficile Infection Diagnosis by Biological Molecular Methods",slug:"clostridium-difficile-infection-diagnosis-by-biological-molecular-methods",totalDownloads:1956,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In the past 15 years, the incidence of Clostridium difficile infection has emerged especially because of the new highly virulent strains. The classical diagnosis methods used to diagnose C. difficile infection take time and the enzyme immunoassay (EIA) test has demonstrated the lack of sensitivity. Even though new modern molecular methods have become available, the diagnosis of C. difficile in patients or healthy carriers remains a big challenge for both clinicians and laboratory staff. In the present chapter, we will list the main genotyping methods, stressing their advantages and disadvantages, as well. A brief presentation of the most useful kit (principle, sensitivity, specificity, benefits and disadvantages) to assess the impact of molecular methods in comparison with classical methods will offer support for future research in the present context of an increasing prevalence of C. difficile infection that represents worldwide, a real public health problem. To improve the patients’ quality of life, to limit hospital transmission, and to save money, we have tried to identify the best diagnosis algorithm as tool in C. difficile diagnosis and surveillance. This algorithm may differ depending on the capacities of the laboratories and on the socioeconomic level of the countries in question.",book:{id:"5831",slug:"clostridium-difficile-a-comprehensive-overview",title:"Clostridium Difficile",fullTitle:"Clostridium Difficile - A Comprehensive Overview"},signatures:"Luminiţa Smaranda Iancu, Andrei Florin Cârlan and Ramona\nGabriela Ursu",authors:[{id:"197809",title:"Prof.",name:"Luminiţa Smaranda",middleName:null,surname:"Iancu",slug:"luminita-smaranda-iancu",fullName:"Luminiţa Smaranda Iancu"},{id:"205531",title:"Dr.",name:"Andrei",middleName:null,surname:"Cârlan",slug:"andrei-carlan",fullName:"Andrei Cârlan"},{id:"205532",title:"Dr.",name:"Ramona Gabriela",middleName:null,surname:"Ursu",slug:"ramona-gabriela-ursu",fullName:"Ramona Gabriela Ursu"}]},{id:"53782",title:"Methicillin-Resistant Staphylococcus aureus (MRSA) in Food- Producing and Companion Animals and Food Products",slug:"methicillin-resistant-staphylococcus-aureus-mrsa-in-food-producing-and-companion-animals-and-food-pr",totalDownloads:2728,totalCrossrefCites:8,totalDimensionsCites:16,abstract:"Methicillin-resistant Staphylococcus aureus (MRSA) has become a growing concern in companion and food-producing animals. The presence of multidrug-resistance with a wide range of extracellular enterotoxin genes, virulence factors, and Panton-Valentine leukocidin (pvl) cytotoxin genes confer life-threatening traits on MRSA and makes them highly pathogenic and difficult to treat. Clonal complex 398 (CC398), a predominant clonal lineage of livestock-associated-MRSA in domestic animals and retail meat, is capable of infecting humans. In order to monitor and prevent MRSA contamination, it is critical to understand its source and transmission dynamics. In this review, we describe MRSA in food-producing animals (pig, cattle, chicken), horses, pet animals (dogs, cats), and food products (pork, beef, chicken, milk, and fish).",book:{id:"5471",slug:"frontiers-in-i-staphylococcus-aureus-i-",title:"Frontiers in Staphylococcus aureus",fullTitle:"Frontiers in Staphylococcus aureus"},signatures:"Jungwhan Chon, Kidon Sung and Saeed Khan",authors:[{id:"189634",title:"Dr.",name:"Kidon",middleName:null,surname:"Sung",slug:"kidon-sung",fullName:"Kidon Sung"},{id:"190400",title:"Dr.",name:"Jungwhan",middleName:null,surname:"Chon",slug:"jungwhan-chon",fullName:"Jungwhan Chon"},{id:"190401",title:"Dr.",name:"Saeed",middleName:null,surname:"Khan",slug:"saeed-khan",fullName:"Saeed Khan"}]},{id:"55751",title:"Overview of Clostridium difficile Infection: Life Cycle, Epidemiology, Antimicrobial Resistance and Treatment",slug:"overview-of-clostridium-difficile-infection-life-cycle-epidemiology-antimicrobial-resistance-and-tre",totalDownloads:2720,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"The use of antimicrobial agents and acquired resistances explains in part the emergence and spreading of epidemic strains of Clostridium difficile. Continued use of antimicrobial therapy still represents an acute danger in triggering the emergence and spreading of new resistant and multiresistant strains including against first-line antibiotics. We examine the pathway of peptidoglycan synthesis in this organism and associated resistances, as well as resistance to other classes of antibiotics. The life cycle of C. difficile involves growth, spore formation and germination. Spores endow the organism with a formidable capacity of persistence in the environment and in the host, resistance, dissemination and infectious potential. Highly resistant spores produced by antibiotic-resistant/multiresistant strains may be one of the most serious challenges we face in what concerns the containment of C. difficile. Finally, we review recent developments in the treatment and prevention of C. difficile infection.",book:{id:"5831",slug:"clostridium-difficile-a-comprehensive-overview",title:"Clostridium Difficile",fullTitle:"Clostridium Difficile - A Comprehensive Overview"},signatures:"Joana Isidro, Aristides L. Mendes, Mónica Serrano, Adriano O.\nHenriques and Mónica Oleastro",authors:[{id:"164933",title:"Prof.",name:"Mónica Alexandra",middleName:null,surname:"Sousa Oleastro",slug:"monica-alexandra-sousa-oleastro",fullName:"Mónica Alexandra Sousa Oleastro"},{id:"200015",title:"Dr.",name:"Joana",middleName:null,surname:"Isidro",slug:"joana-isidro",fullName:"Joana Isidro"},{id:"200016",title:"MSc.",name:"Aristides",middleName:null,surname:"Mendes",slug:"aristides-mendes",fullName:"Aristides Mendes"},{id:"200017",title:"Prof.",name:"Mónica",middleName:null,surname:"Serrano",slug:"monica-serrano",fullName:"Mónica Serrano"},{id:"200019",title:"Prof.",name:"Adriano",middleName:null,surname:"Henriques",slug:"adriano-henriques",fullName:"Adriano Henriques"}]}],onlineFirstChaptersFilter:{topicId:"906",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"May 19th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!1,editor:null,editorTwo:null,editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",isOpenForSubmission:!0,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. 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Beloborodova",profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",slug:"oxidoreductase",publishedDate:"February 17th 2021",editedByType:"Edited by",bookSignature:"Mahmoud Ahmed Mansour",hash:"852e6f862c85fc3adecdbaf822e64e6e",volumeInSeries:19,fullTitle:"Oxidoreductase",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour",profilePictureURL:"https://mts.intechopen.com/storage/users/224662/images/system/224662.jpg",institutionString:"King Saud bin Abdulaziz University for Health Sciences",institution:{name:"King Saud bin Abdulaziz University for Health Sciences",institutionURL:null,country:{name:"Saudi Arabia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9742",title:"Ubiquitin",subtitle:"Proteasome Pathway",coverURL:"https://cdn.intechopen.com/books/images_new/9742.jpg",slug:"ubiquitin-proteasome-pathway",publishedDate:"December 9th 2020",editedByType:"Edited by",bookSignature:"Xianquan Zhan",hash:"af6880d3a5571da1377ac8f6373b9e82",volumeInSeries:18,fullTitle:"Ubiquitin - Proteasome Pathway",editors:[{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9002",title:"Glutathione System and Oxidative Stress in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9002.jpg",slug:"glutathione-system-and-oxidative-stress-in-health-and-disease",publishedDate:"August 26th 2020",editedByType:"Edited by",bookSignature:"Margarete Dulce Bagatini",hash:"127defed0a50ad5ed92338dc96e1e10e",volumeInSeries:17,fullTitle:"Glutathione System and Oxidative Stress in Health and Disease",editors:[{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Proteomics",value:18,count:3},{group:"subseries",caption:"Metabolism",value:17,count:6},{group:"subseries",caption:"Cell and Molecular Biology",value:14,count:8},{group:"subseries",caption:"Chemical Biology",value:15,count:10}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:3},{group:"publicationYear",caption:"2021",value:2021,count:7},{group:"publicationYear",caption:"2020",value:2020,count:12},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:2}],authors:{paginationCount:301,paginationItems:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. 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