Summary of clinical reports describing hearing loss in PDE5- and interferon-treated patients.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"7991",leadTitle:null,fullTitle:"Understanding the Molecular Crosstalk in Biological Processes",title:"Understanding the Molecular Crosstalk in Biological Processes",subtitle:null,reviewType:"peer-reviewed",abstract:"It is essential to address the aspects related to the crosstalk approach in understanding complex biological processes in different organisms, including plants, microorganisms, animals, and humans. 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The sense of hearing is fundamental to the communication and proper reaction to dangerous situations. Moreover, recent studies indicated that the hearing loss increases significantly the risk of dementia [1]. Unfortunately, people’s ability to hear deteriorates with time, as the human auditory epithelium is post-mitotic and unable to regenerate. In other words, the few thousand of auditory hair cells with which we are born have to last our entire life. There are several causes of hearing loss such as noise, aging, infections, tumors, neuronal degeneration or cardiovascular diseases. Another important cause of hearing loss is ototoxicity.
\n\nIn this chapter, we will concentrate on medications that are known to induce hearing loss as an adverse effect. These medications are also known as ototoxic medications.
\nClinical signs of ototoxicity may include at least one of the following symptoms:
\ntinnitus
hearing loss (unilateral or bilateral)
vertigo.
First signs of ototoxicity usually develop during or shortly after receiving particular medication. Majority of ototoxic drugs induces irreparable damage translating into permanent hearing loss; however, aspirin and derivatives belong to drugs that cause most of the times reversible hearing loss [2]. In fact, aspirin-induced ototoxicity in form of tinnitus was used for decades by rheumatologists to adjust the maximal therapeutic dose of salicylates in the patients. This practice was abandoned because of poor correlation between salicylate blood levels and ototoxicity symptoms [3] and because of development of new drugs used for the treatment of rheumatic diseases. Nevertheless, even today there are patients occasionally admitted to the emergency room because of the salicylate-induced ototoxicity [4]. The ototoxicity of salicylate has been attributed to its capacity to bind and inhibit the action of cochlear protein prestin, expressed by the outer hair cells [5, 6]. In addition, salicylate can induce death of spiral ganglion neurons as well as cause dysregulation in the central auditory pathway [7].
\nOther groups of well-known ototoxic drugs that frequently cause hearing loss include:
\nplatinum-based cytostatic drugs
aminoglycoside antibiotics
loop diuretics
Platinum-based cytostatics (cisplatin, carboplatin and oxaliplatin) are used as single agents and in combination with other drugs for the treatment of various types of cancer (e.g., testicular carcinoma, lung carcinoma, ovarian carcinoma, head and neck carcinomas, melanomas, lymphomas and neuroblastomas) [8]. The platinum-based drugs bind DNA and induce irreversible changes that prohibit tumor cell division. However, common adverse effects of platinum-based drugs include nephrotoxicity and ototoxicity. This toxicity is being attributed to an excessive production of reactive oxygen species that leads to death of auditory hair cells [9–11]. Clinically, patients develop permanent bilateralhearing loss that originates in high frequencies [12]. In addition, patients may have difficulties with speech understanding in noise [13].
\nAminoglycosides are a group of antibiotics used to treat gram-negative bacterial and mycobacterial infections. Clinically used aminoglycosides include amikacin and kanamycin (primarily cochleotoxic) as well as gentamicin, streptomycin and tobramycin (primarily vestibulotoxic) [14]. Similar to the ototoxic mechanism of platinum-based drugs, aminoglycosides induce excessive formation of free oxygen species followed by apoptosis of sensory hair cells [10, 15]. The aminoglycoside-induced hearing loss is bilateral and permanent and starts in the high frequencies. Precisely because of its ototoxic properties, gentamicin is frequently used for the treatment of Ménière’s disease in the form of intratympanic injections to deplete the vestibular hair cells and thus, to prevent frequent vertigo attacks.
\nOf note: About 30% of the world population is infected with Mycobacterium tuberculosis [16]. The treatment of tuberculosis (especially that caused by multiple-drug resistantMycobacterium tuberculosis) includes intravenous administration of so-called ond-line antibiotics–amikacin, kanamycin and streptomycin–leaving at least 20% of the patients with serious permanent hearing impairment [17].
\nLoop diuretics are a group of drugs that inhibit renal reabsorption of sodium, chloride and potassium. They are often used to treat kidney insufficiency or heart failure. Loop diuretics include furosemide, bumetanide, ethacrynic acid and torsemide. Their ototoxic mechanism involves inhibition of potassium resorption occurring in the stria vascularis and consequent decrease in the endocochlear potential [18]. The hearing loss induced by loop diuretics is bilateral and usually reversible; however, since loop diuretics are known to synergize with platinum-based drugs or with aminoglycosides in their ototoxic action, in patients receiving drugs from both groups, loop diuretics may worsen the degree of permanent hearing loss [19–21].
\nThere is a growing number of case reports and larger studies indicating that the family of ototoxic drugs is growing and embraces newly developed medications. Although the ototoxic properties of several pharmacological drugs were recently compiled in an excellent review written by Cianfrone et al. [22], the clinical information changes and requires update.
\nIn this chapter, we review selected group of frequently used, contemporary pharmacological drugs (phosphodiesterase-5 blockers and antiviral drugs (see Table 1), painkillers and immunosuppressants) in aspect of audiologically important adverse reactions including hearing loss and tinnitus.
The class of medication | Type of report | Presence of tinnitus | Type of hearing loss | Measuring method | Reversibility of hearing loss | References |
---|---|---|---|---|---|---|
PDE5 inhibitors | Case report (1 subject) | Not stated | Profound bilateral sensorineural hearing loss | Pure tone audiometry; impedance audiometry; stapedial reflex absent on both sides | No | [23] |
Prospective study (21 subjects) | Not stated | Unilateral sensorineural hearing loss 1 h after injection of drug | Pure tone audiometry | Yes | [24] | |
Analysis of 47 case reports (pharmacovigilance) | Not stated | Unilateral or bilateral sensorineural hearing loss | Not stated | In some cases, yes; in others long-term impairment | [26] | |
Case report (2 subjects) | Yes | Unilateral sensorineural hearing loss | Pure tone audiometry, ABR | In one case, yes | [27] | |
Interferons | Prospective study (before/after) 49 subjects | Yes | Sensorineural hearing loss | Pure tone audiometry, tympanometry (normal) | Yes | [30] |
Case report (3 subjects) | Yes | Unilateral sensorineural hearing loss | Pure tone audiometry | Yes (2 cases), no (1 case) | [31] | |
Prospective study (before/after) 73 subjects | Yes | Sensorineural hearing loss | Pure tone audiometry | Yes | [31] | |
PEG interferons | Prospective study (before/after) 21 subjects | Not stated | None found | Pure tone audiometry, DPOAE | Not applicable | [35] |
Case report (1 subject) | Not stated | Unilateral hearing loss | Not stated | Yes | [36] | |
Case report (1 subject) | Yes | Unilateral hearing loss | Not stated | No | [37] | |
Case report (6 subjects) | Yes (4 of 6) | Five subjects developed unilateral and one bilateral sensorineural hearing loss | Pure tone audiometry | No improvement in three cases, some improvement in two cases, no data in one case | [38] |
Summary of clinical reports describing hearing loss in PDE5- and interferon-treated patients.
Although in the industrialized countries, the hepatitis C and B therapy with pegylated or non-pegylated interferons and ribavirin is being replaced by other pharmacological regimes, one should not ignore the fact that not all countries and hospitals have adopted the new routine and that the interferons are still in use, possibly contributing to drug-related hearing loss.
PDE5 inhibitors block the phosphodiesterase-5 in the smooth muscle cells lining the blood vessels in the cardiovascular system. Phosphodiesterase-5 degrades cyclic GMP, regulating smooth muscle tone. The first PDE5 inhibitor–sildenafil–was introduced in the market in 1998 under the name Viagra. PDE5 inhibitors are used for the treatment of erectile dysfunctions and for pulmonary artery hypertension.
\nIn the year 2007, an alarming report was published by Mukherjee and Shivakumar, in which a case of bilateral profound sensorineural hearing loss was described in 44-year-old man who took 50 mg/day of sildenafil for 2 weeks [23]. Based on that report, FDA issued a warning about possible sudden hearing loss among users of PDE5 inhibitors.
\nOver the past 10 years, evidence suggesting negative influence of PDE5 inhibitors on hearing has accumulated. In a clinical study, Okuyucu et al. [24] reported significant but reversible unilateral hearing loss in four of 18 patients taking PDE5 inhibitors. The hearing loss affected the right ear at 10,000 Hz (p = 0.008).
\nMuch larger epidemiological study published 1 year later by McGwin [25] evaluated the relationship between hearing loss and the use of PDE5 inhibitors in a population-based sample. This USA-based study was designed using self-reported hearing impairment and PDE5i use and included over eleven thousand men who were 40 years or older. Results of this study indicated that men with hearing loss are more than twice as likely to use PDE5 inhibitors, when compared with those not reporting hearing loss. However, no causal relationship could be established in that study.
\nIn 2011, Khan et al. [26] published a report based on data provided by pharmacovigilance agencies Europe, the Americas, East Asia and Australasia, and on published reports. The authors identified among PDE5 inhibitor users 47 cases of sensorineural hearing loss, most of them unilateral. Almost 70% of the subjects (mean age 56.6 years, men-to-women ratio 7:1) reported hearing loss within 24 h after ingestion of PDE5 inhibitors.
\nIn 2012, unilateral sudden sensorineural hearing loss affecting two male PDE5 inhibitor users (age 37 and 43) was described by Barreto and Bahmad [27]. Unfortunately, neither the time after the hearing loss has occurred nor the dosage of PDE5 inhibitors was stated. In addition to the hearing loss, both patients were affected by vertigo and tinnitus. After combination therapy consisting of steroids administered orally and intratympanically, one of the patients recovered partially, whereas the other one was left with permanent profound sensorineural hearing loss.
\nThe causal relationship between the PDE5 inhibitors and (sudden) sensorineural hearing loss remains to be confirmed using experimental models. Au and colleagues using the animal model (C57BL/6J mice) and sildenafil (Viagra) were unable to find the differences in hearing thresholds between the drug- and placebo-treated animals [28]. However, other functional studies in mice with the use of osmotic pumps for drug release demonstrated that the inner ear of animals exposed to sildenafil reacted with hydrops [29].
\nThe epidemiological and case report data indicate that PDE5 inhibitors may have general negative impact on hearing. Moreover, PDE5 inhibitors may induce sudden sensorineural hearing loss that in some cases can be successfully treated with corticosteroids; in some other cases, the patients recover without any treatment; and lastly, it can also leave patients with permanent hearing impairment.
Interferons (IFN) are a group of naturally occurring proteins that are released by several cell types in response to infection or tumors. There are three classes of interferons: type I, type II and type III. Type I interferons include IFN-alpha and IFN-beta. Synthetic and recombinant interferons, alpha and beta, have been used for therapy of viral infections with hepatitis C or B virus. In addition, IFN-beta can be used to treat multiple sclerosis.
\nOne of the first reports associating interferon treatment with hearing loss was published in 1994 [30]. In that report, a group of 49 patients (32 men and 17 women, mean age 48.6, age range 23–67) receiving various brands of interferons for chronic hepatitis B or C were assessed with pure tone audiometry before the onset of treatment and then in consecutive 1-week interval. In case of IFN-alpha, the drug was administered i.m. each day for 2 weeks and then three times a week for 14–22 weeks. In case of IFN-beta, the drug was administered i.v. daily for 6 weeks. The study demonstrated that 45% (22 patients) developed auditory dysfunction: 14 patients (29%) reported having tinnitus and 18 patients (35%) were diagnosed with sudden sensorineural hearing loss. More than half (56%) of the patients treated with interferon-beta (total of 27 subjects) developed auditory disability with unilateral or bilateral hearing loss affecting various frequencies diagnosed in 11 patients (41%). In the group treated with IFN-alpha (total of 22 subjects), seven developed unilateral hearing loss affecting 8000 Hz. Progressive hearing loss leads in two cases to withdrawal from therapy. There was no association between the clinical parameters such as proteinuria, leucopenia, liver functions and the hearing loss. Interestingly, all patients recovered within 2 weeks after finishing the interferon treatment.
\nPublished 1 year later, prospective audiological study of 73 patients treated with IFN-alpha or IFN-beta for hepatitis confirmed the above observations, including the hearing loss exclusively affecting 8000 Hz in patients receiving IFN-alpha [31]. There was, however, one difference: in the larger sample studied, the hearing abilities of one patient have not recovered after discontinuation of therapy. Later, studies confirmed majority of these observations [32] and most importantly the general reversibility of ototoxic effects of IFN-alpha [33].
\nInteresting mechanistic insights of IFN-alpha-induced ototoxicity were delivered from studies using mouse model [34]. There was an elevated ABR threshold in mice treated with IFN-alpha as compared to untreated control group. Moreover, histological findings of cochleae dissected from experimental animals indicated abnormalities in the number (lower) and appearance (cytoplasmic vacuolization) of the spiral limbus fibroblasts in the IFN-alpha-treated mice. These findings point to direct negative effect of IFN-alpha on cochlear biology, which may result in the hearing loss.
Pegylated interferons are chemically “improved” interferons bound to polyethylene glycol (PEG). Pegylation assures longer half-time of interferons in the body. There are three groups of pegylated interferons available in the market–pegylated interferon-alpha-2a (PEG-IFNa2a), pegylated interferon-alpha-2b (PEG-IFNa2b) and pegylated interferon-beta-1a.
\nRibavirin is a guanosine analog (nucleoside inhibitor) that stops viral RNA synthesis. It is used to treat various viral hemorrhagic fevers, and it is the only known drug against rabies. Although new therapeutic approaches are being introduced on the healthcare market for the treatment of hepatitis C (e.g., protease inhibitor telaprevir or boceprevir), ribavirin in combination with PEG-IFN-alpha is still a part of the current standard of care (SOC) therapy in some countries and it is also included in the new therapeutic regime.
\nTherapeutic use of PEG-IFN and ribavirin in hepatitis C infections induces similar otological effects as the therapy with non-pegylated interferons only. However, there is one major difference: the hearing abilities do not recover in the majority of cases. Although some reports describe no hearing disabilities [35] or sudden unilateral sensorineural hearing loss resolving spontaneously within 2 weeks after the end of treatment [36], some other demonstrate that patients may develop irreversible unilateral hearing loss [37] or irreversible unilateral pantonal hearing loss (measured by pure tone audiometry) and tinnitus [38].
According to the United Nations AIDS organization, approximately 36.7 million people worldwide are infected with the HIV virus. The patients with HIV are treated with drugs that inhibit the virus proliferation. Since HIV virus uses very unique enzyme to copy its genome, this enzyme–reverse transcriptase–is a pharmacological target of anti-HIV therapy. The unique thing about the HIV therapy is that it should never be stopped, even if the viral load is undetectable.
\nThe discovery and the beginning of clinical application of reverse transcriptase inhibitors date back to the eighties last century. The first reports about their negative effect on hearing appeared some 10 years later and ever since conflicting conclusions are being drawn from several studies. In some studies, authors found the hearing loss among 30% of HIV patients taking the reverse transcription inhibitors [39–41], whereas in other studies, no association between audiological impairment and antiviral medication was found [42, 43]. Various inclusion criteria, diverse outcome measure methods, sample size and many other factors could contribute to these dissimilar results.
\nIn the controlled environment of experimental laboratory, the results look much more uniform and point at universal ototoxicity of all types of reverse transcriptase inhibitors that are on the market, as measured by the viability of auditory epithelial cell line exposed to various concentrations of 14 types of pharmacological reverse transcription inhibitors as single agents and in combination, as used in the clinics [44].
Paracetamol, also known as acetaminophen (in the USA and Canada) or APAP, is the most commonly used pain killer in North America and Europe. It inhibits selectively cyclooxygenase-2 (COX-2) and may also exert other pain-relieving functions. Recent studies on self-reported professionally diagnosed hearing loss and use of analgesics indicated that regular use of paracetamol significantly increases the risk of hearing loss in men [45] and women [46]. The large size of samples with which the studies were performed (26,917 men and 62,261 women) makes both studies particularly credible.
\nThe main conclusion from this study was that the long-term use of paracetamol (acetaminophen) increases the risk of developing hearing loss in men and women.
\nThe mechanism of paracetamol-induced hearing loss was experimentally addressed in vitro [47]. The authors demonstrated that in the mouse auditory epithelium cell line, paracetamol and its metabolite NAPQI (N-acetyl-p-benzoquinoneimine) induce ototoxicity by causing oxidative stress as well as endoplasmic reticulum (ER) stress. These basic research results possibly explain the ototoxicity seen in people who regularly consume paracetamol. The question about usage of paracetamol and its frequency should be included in the surveys/questionnaires of patients with otologic and audiologic considerations.
\nHydrocodone is a semi-synthetic opioid used for pain therapy and in common anti-cough medications. Hydrocodone is often prescribed in combination with paracetamol. In a report describing 12 patients with a history of hydrocodone overuse and progressive irreversible sensorineural hearing loss, the authors implicated nonresponsiveness of this type of hearing loss to corticosteroid therapy [48]. The authors reported that seven of eight patients who underwent consecutive cochlear implantation benefited from this type of auditory rehabilitation. Similar recent case report described a patient with unilateral hearing loss attributed to abuse of hydrocodone and paracetamol [49]. Also this patient was treated with cochlear implant.
\nThe information delivered from the in vitro model with auditory epithelial cell line suggested that the combination of hydrocodone and paracetamol results in ototoxicity not due to hydrocodone but rather due to paracetamol [50]. The authors suggested that the contribution of hydrocodone to clinically seen ototoxicity may lay in hydrocodone assisting the addiction to the drug combination.
Methadone is an opioid drug for treating pain. In addition, it is used for therapy of people addicted to opioids.
\nIn the year 2014, about 7 million US citizens were abusing prescription drugs (source: National Center for Health Statistics). One of these drugs is methadone. Six recent case reports exposed an unknown before side effect of methadone abuse–the hearing loss [51–55]. The patients described in reports were young (age range 20–37) and were admitted to the hospitals because of methadone overuse. In all reported cases, the patients were deaf upon awakening (one perceived tinnitus), and in four of six cases, hearing loss was only temporary condition. The remaining two patients were unfortunately left with severe sensorineural hearing loss for the remaining observation time (2 and 9 months).
Since the beginning of transplantology in the sixties, several people with incurable diseases of liver, kidney and other organs received the donor tissues as therapeutic procedure. This type of therapy is combined with an inevitable immune reaction against the non-self tissue. To prevent these reactions, immunosuppressants are used. Among them, cyclosporine A and tacrolimus (FK506) are commonly used to prevent graft rejection reaction. Both drugs decrease in various ways the activation of lymphocytes T and thus inhibit the graft rejection process. The immunosuppressants must be taken continuously.
\nRifai et al. [56] performed a large study involving 521 liver transplant patients. The study was based on self-reported hearing loss and showed that of 521 individuals, 141 (27%) developed hearing loss following transplantation, particularly in those patients who were receiving tacrolimus as principal immunosuppression. This study was followed by recent trial, where instead of self-reported hearing loss, audiometric measurements were performed [57]. Of 70 liver transplant patients included in that study, 32 reported hearing loss and tinnitus following the transplantation. The types of hearing loss included sudden hearing loss and progressive hearing loss, which developed more than 3 years after transplantation. Audiometry confirmed the patients’ reports and identified 12 patients with mild, 28 with moderate and 25 with severe hearing loss following the transplantation. The association between tacrolimus and hearing loss was seen again in this study.
\nAnother group of transplant patients is the renal transplant group. Kidney transplantation is a surgical procedure performed since the mid-fifties last century; however, postsurgical survival was very low, because of the graft rejection [58]. The introduction of cyclosporine A in the eighties significantly improved the post-transplant survival rate but brought another type of problems, namely adverse reactions such as hearing loss. Renal patients are known to often have hearing impairments [59], and it was shown that the renal transplantation restores the hearing abilities, when measured 1 year after surgery. However, some renal transplant patients who are on a long-term immunosuppressant therapy such as cyclosporine A or tacrolimus develop hearing disabilities including sudden sensorineural hearing loss [60–62] or a progressive hearing loss [63].
\nParticularly, worrying tendency is seen among the pediatric renal transplant patients. A prospective study of 27 children (mean age 14) with normal hearing prior to kidney transplantation determined after a mean follow-up of 30 months that 17 children developed sensorineural hearing loss [60]. Two of 17 children were diagnosed with sudden hearing loss and the rest of the group with a progressive bilateral hearing loss.
\nIt is likely that the ototoxic effect of immunosuppressants depends on the length of time of intake. Groups studying noise-induced hearing loss have successfully used cyclosporine A and tacrolimus to protect the auditory epithelium in mice from the noise-induced injury [64]. However, the dosage was single and not–like in the case of transplant patients–years long.
\nThe treatment of hearing impairment occurring in organ transplant recipients includes hearing aids and cochlear implantation [65]. However, one should not ignore the fact that these patients are immunocompromised, and therefore, the risk of wound infection after CI should be taken under consideration during postsurgical management.
The auditory system requires a lot of energy produced in mitochondria [66–69]. Mitochondrial pathologies induced by genetic mutations are often associated with hearing loss [70–72]. Similarly, substances known to damage mitochondria such as aminoglycosides or cisplatin are known as ototoxic and contribute significantly to the hearing loss and tinnitus [73].
\nThe substances listed in the present chapter can all damage the mitochondria. The damaging mechanism varies, and for instance, IFN-alpha impairs the transcription of mitochondrial DNA, whereas nucleoside analogues impair the replication of mitochondrial DNA [74]. In agreement with this, severe mitochondrial toxicity manifested by hyperlactatemia and pancreatitis was described in some cases involving patients with HIV/hepatitis C virus treated with pegylated interferon and ribavirin [75]. Paracetamol was also shown to have negative effect on mitochondria by inducing overproduction of reactive oxygen species (ROS) and inducing endoplasmic reticulum stress [47, 76]. Methadone was shown to impair synthesis of mitochondrial ATP leading to bioenergetics crisis of the affected organism [77]. The reverse transcriptase inhibitors used to slow down the replication of HIV virus were likewise demonstrated to induce mitochondrial toxicity [78, 79]. Lastly, cyclosporine A was shown to inhibit adenine nucleotide net transport into the mitochondria [80], whereas tacrolimus was associated with decreasing the levels of oxidative phosphorylation in mitochondria [81].
\nSince the negative effect of various drugs on mitochondria likely results in a damage of hearing, it is plausible that the mitochondria-supporting substances (such as coenzyme Q10, vitamin B12 with folic acid, sirtuin and many others) given as auxiliary therapy could protect the sense of hearing in patients with hepatitis, HIV, transplant patients or painkiller or PDE5 inhibitor users. In fact, targeting mitochondria is becoming increasingly popular [82], and there were some successful attempts in treatment of hearing conditions using mitochondrial supplements [83–89].
The appearance of new drugs to treat ever more conditions is an inevitable and welcomed progress of medical and pharmaceutical sciences. However, assuring the drug safety in terms of hearing disability is difficult, and it often requires very long and regular intake periods, which are outside of regular phase I, II or III clinical trials. As for the duration of phase IV (the postmarketing surveillance trials), which is usually set for 2 years, perhaps it could be extended specifically for the monitoring of audiological conditions.
\nThe ototoxicity of prescription or over-the-counter drugs is a global problem. Collaboration between audiologists or otologists and other healthcare providers is necessary to protect the patient’s auditory health. Auditory consultations ought to be a routine during the treatment of patients with viral hepatitis C or B receiving interferons and ribavirin or HIV-positive individuals taking anti-reverse transcriptase drug cocktail. Moreover, patients undergoing solid organ transplantation should be audiologically monitored. The option of audiological care for children treated for any of the above infectious diseases or undergoing transplantation should be presented to their parents. Lastly, frequent users of painkillers and recreational drugs should be informed about the risks of the medications they are reaching for every day.
\nDuring the unavoidable drug therapies, preventive means such as mitochondrial protection and supplementation during the drug treatment and audiological monitoring as well as fitting the patients with hearing aids or cochlear implants, could help to keep the hearing healthy or at least to restore it to some degree.
\nThe good condition of hearing is as important as that of heart, lung or other organs. Informing the community about ototoxicity and keeping up to date with the case reports and other scientific communications may help to save the sense of hearing.
Cyclosporine A | Fungal metabolite that suppresses immune reaction. It inhibits the activation of lymphocytes T by binding to cyclophilin and inhibiting calcineurin |
Endocochlear potential | Voltage of +80mV in the scala media, generated by the stria vascularis, essential for the auditory transduction |
Interferon (IFN)-alpha | Small signaling protein produced and released mainly by white blood cells in response to viral infection |
Interferon (IFN)-beta | Small signaling protein produced and released mainly by fibroblasts in response to viral infection |
Intratympanic injections | Injections through the eardrum into the middle ear cavity |
Mycobacterium tuberculosis | Infectious microorganism causing tuberculosis |
Nucleoside | Glycosylamine (e.g., cytidine, uridine, adenosine, guanosine or thymidine), primary DNA or RNA molecule. Also known as nucleotide without phosphate group |
Phosphodiesterase-5 (PDE5) | Enzyme that catalyzes the hydrolysis of cyclic GMP and regulates tonus of smooth muscle cells |
PDE5i | Phosphodiesterase-5 inhibitors |
Polyethylene glycol (PEG) | Polymer of ethylene oxide. PEG can be bound to proteins, therefore slowing their decay time in the body |
Protease inhibitor | Inhibitor of enzymes that degrade proteins. Viral proteases are essential for viruses to complete their life cycle |
Reverse transcriptase (RT) | Enzyme that synthesizes DNA using as a template RNA, a process called reverse transcription. This process is specific for viral replication and is used for instance by HIV virus |
Tacrolimus (FK-506) | Bacterial derivative isolated from Streptomyces tsukubaensis. Tacrolimus inhibits activation of lymphocytes T via inhibiting calcineurin. Similar but not identical in action to cyclosporine A |
Among the many lessons being learnt from the ongoing coronavirus disease 2019 (COVID-19) pandemic is that the state of health of each country may be intricately linked to all other countries on the globe. This comes to buttress what the world witnessed during epidemics in the recent past, particularly the Ebola virus disease of 2014–2016. Impliedly, whatever happens in the health system of any country in the 21st century is likely to have some effect on many other countries due to the high interconnectedness and interdependence of our world. Frequent and rapid travel possibilities have facilitated movement of disease causing agents such as seen in the emergence of COVID-19. Millions of lives and properties are lost in the wake of infectious diseases. Infectious diseases may have killed more humans than wars have ever done in human existence. These call for strengthening international health security especially in resource-constraint regions of the world so as to fight future epidemics and other diseases. This may be done by instituting appropriate healthcare policies based on local contexts and establishment of requisite healthcare infrastructure. Also, the World Health Organisation (WHO) should be strengthened and resourced as well as a demonstration of a high sense of commitment on the part of countries to adhere to international health treaties [1, 2].
\nEmerging health threats are constituted by a number of new, unknown and evolving health conditions that a group of people encounter every now and then. These complications may result from environmental destruction, infectious diseases, population and lifestyle events, chemical exposure and natural disasters. The possibility of deliberate or accidental release of pathogens as bioweapons should also not be lost on us. These health threats may be faced from time to time and their effects may be experienced on a daily basis. Additionally, the emerging burden of disease in Africa, a resource-constraint region, shows a trend in which the predominantly infectious disease-burdened region is now grappling with non-communicable diseases [3].
\nIn the midst of the deadly COVID-19 pandemic, resource-scarce countries may potentially marshal some inherent resources to combat emerging health threats. While the availability of a full functioning and inclusive healthcare system is desirable in all countries including low- and middle- income countries (LMICs), to effectively tackle emerging and re-emerging health threats, LMICs may start off by strengthening their low-level resources while scaling up with the construction of the needed huge infrastructural healthcare facilities.
\nAs being witnessed in some places, particularly in developing countries, readiness of the populace to follow through with the COVID-19 protocols without extreme recourse to challenging the need for instituting those protocols vis-à-vis infringement on human rights, disease mitigating measures have the potential to achieve worthwhile results in the direst of circumstances. This is contrary to what transpired in the West, especially in the early days of the emergence of COVID-19, where there were elaborate roadblocks set in the path of these same protocols. For instance, while the generality of the Ghanaian population, and indeed some parts of Africa, largely accepted and embraced the wearing of face masks and used same as a fashion trend, that was to be missing in the West.
\nIn protecting a country’s health security, the said country is indirectly contributing to protecting and promoting international health. Unfortunately, about 70% of the world’s countries assert that they cannot independently fight off an outbreak [4]. This calls for urgent steps in scaling up the healthcare resources of these countries. Technical and financial assistance for epidemic preparedness should be advocated and closely monitored. For example, intensive personnel training, spearheaded by the Centres for Disease Control and Prevention (CDC), highly contributed to Nigeria’s success at fighting the 2014 EBOLA epidemic [5]. Prevention, early detection and treatment are the surest and most efficient ways to fight off epidemics. Despite advanced countries have the moral obligation to assist their less-developed counterparts, owing to our interdependence, the latter needs to harness local resources aimed at achieving same target.
\nGood health is essential for the full functionality of humans. Determinants of quality and adequate health security of a population include a number of factors. These include the availability of a well-laid out quality healthcare policy and programmes, health facilities including hospitals and fully-functional diagnostic laboratories as well as a qualified and highly-motivated healthcare workforce. The availability of these varies from place to place, globally.
\nHealth security in the developed world is one of topmost priority to governments in those countries. In such places, there is massive investment in both basic and applied health research, for example. The availability of comprehensive healthcare policy complemented with advanced, state-of-the-art healthcare infrastructure enabled these countries to adequately provide for the health needs of their people. Such countries have effective and elaborate surveillance system in place to quickly identify any emerging health threat and provide the necessary remedy in a timely and effective manner, in most stances. When they even delay in doing so, it sounds to reason that the turn-around time would have even be higher should same condition be found in the developing world.
\nIn resource-scarce regions of the world such as parts of Africa and Asia, however, there is a wide gap in providing the essentials needed for quality healthcare. These affect the overall quality of healthcare services rendered to people in these areas. More importantly, should there be an epidemic such as the EBOLA virus disease of 2014–2016 in parts of West Africa, there might be dare consequences for the lives of people not only in the epicentres of the infections but potentially, everywhere else.
\nInadequate healthcare infrastructure to combat infectious disease outbreaks is a major occurrence in many LMICs. Despite the need for foreign aids to scale-up the number of key healthcare infrastructures in LMICs, these should not in any way be strictly tied to complicated strings that have the potential to affect the sovereignty and overall human security of these countries.
\nEarly detection of outbreaks, which is essential for containment, takes place in a well-functioning healthcare system [6]. In places where the healthcare system is not properly functioning and where some groups of people do not have access to the country’s healthcare system, outbreaks of infections may go undetected and unreported for months hence causing more havoc in the population. This may occur mostly in developing and resource-scarce countries, as shown by the EBOLA virus disease of 2014 in Guinea, West Africa. Moreover, the implementation of sanctions such as travel bans instead of provision of financial and technical support to countries that report the presence of unusual pathogens and infections in their jurisdictions may deter some of these countries from reporting such outbreaks early enough to world regulatory bodies such as WHO despite being obligated under the international health regulations to report such issues.
\nTo obtain papers for the current work, literature search was conducted in electronic databases and search engines, namely; Google scholar, PubMed and Google search engine. Phrases such as international health security, WHO phases of pandemic, fighting COVID-19 in Africa, second wave of COVID-19 and emerging health threats in Africa were searched. After going through the suggested papers by the searches, the papers used were selected. Papers included were written in English language. Additionally, based on the content of the current chapter, WHO and CDC, two prominent healthcare agencies, were heavily relied on to obtain the requisite papers for the present work.
\nPandemics are marked by phases which identify key observations including their emergence and possible interventions. Similarly, COVID-19 has noticeable phases. These phases are important as they reflect possible preventive and mitigation measures to adopt at any point in the course of the pathogen invasion. For instance, instituting social and physical distancing protocols and the decision to close a country’s borders to traffic (air, land and sea) may be largely influenced by the rate of spread of an epidemic or a pandemic. The COVID-19 phases presented here are based on the WHO pandemic phase descriptions used for influenza [7]. In phase one, no novel coronavirus found in animals was deemed to cause infections in humans hence no need for mitigating measures. In Phase two, however, a novel coronavirus in animals was deemed to be the causative agent of a human infection. Specifically, a pneumonia outbreak with unknown aetiology was noticed in Wuhan city, Hubei province of China in late December, 2019 [8]. Subsequently, this outbreak was found to have commenced at a seafood market in the Wuhan city. Thereafter (12 January 2020), China shared data on a newly discovered coronavirus, initially named 2019 novel coronavirus (2019-nCoV), which was found to cause the pneumonia reported in the previous month.
\nAbout a month later, 11 February 2020, the International Committee on Taxonomy of Viruses (ICTV) officially named the virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and WHO named the condition caused by this virus, coronavirus disease 2019 (COVID-19) [9]. The name of the virus reflects the family of viruses from which SARS-CoV-2 emanates from. Collectively, SARS-CoV-2 together with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) constitute a subfamily of coronaviruses called β-coronavirus, a viral group [10]. Coronaviruses infect both man and animals leading to both acute and chronic conditions [11]. A phase three of the viral spread would be the situation where the virus does not lead to community level transmission because there is no human-to-human contact transmission. Impliedly, the virus in the animal contact may have led to few cases of infection and appropriate containment measures taken to prevent its spread. However, this was not to be the case of COVID-19 as it led to community level or horizontal transmissions. Therefore, phase three of COVID-19 had the virus spreading within the Wuhan city and the Hubei province. Consequently, the first imported case of COVID-19 from Wuhan City, globally, was reported by Thailand on 13 January 2020 [8]. This commenced the cross-country transmission of the disease and phase four of the spread of the pandemic. On 11 March 2020, owing to the over 118,000 confirmed cases in 114 countries in which 4,291 lives were lost, WHO declared COVID-19 a pandemic [12]. This is the Phase five of the spread of the virus.
\nA post-peak period of the pandemic occurs where there is a reduction in pandemic levels (number of cases) in most countries to levels below the observed peak levels. While this might have occurred in specific WHO regions such as Africa (in July), South-East Asia (in September) and Eastern Mediterranean (in November), the global post-peak period is, presently, unknown due to increasing cases in the Americas and across Europe [13]. However, currently, there is a second wave of spread of the virus in which other variants, different from the initially reported strain of the virus, are being found in some countries. With the raging second wave in countries such as the United Kingdom and South Africa, all countries need to strengthen their surveillance as well as mitigating measures so as to avoid the spread of the virus. Finally, a post-pandemic phase will set in when the disease will be reduced to normal levels. During such periods, surveillance and infection preparedness should still be put in place so as to prevent any future outbreak. The WHO phases, largely, correlate with the CDC influenza phases being applied to the surveillance and management of COVID-19 in the United States. These phases are, namely; investigation, recognition, initiation, acceleration, deceleration and preparation with the first four phases termed prepandemic intervals and the remaining, dubbed; pandemic intervals [14].
\nAs at 14 December 2020, globally, there are over 70 million confirmed cases of COVID-19 resulting in about 1.6 million deaths with about 47 million recoveries [15, 16]. The current epicentre of the disease which doubles as the region with the highest number of cases, the Americas, has recorded over 30 million cases, representing about 42% of global infection rate with the United States of America alone accounting for about 16 million of this. Asia, where COVID-19’s patient zero is located, currently falls below Europe based on the number of confirmed cases of COVID-19. The lowest case infection rate, till date, has been recorded in the WHO African region where a total of 1.6 million cases have been reported, that is, about 2.3% of the global infection rate. Similarly, while the Americas have reported 780, 904 deaths so far, the Africa region has reported 35, 879 COVID-19 associated deaths (that is about 2.6% and 2.2% death rate, respectively, in the two regions; both of which are around the global death rate of about 2.3%). There are a number of possibility that may have accounted for the significant variations in the number of cases and deaths reported in the different regions of the world. These may include genetic and temperature variations. Presently, there is a second wave of COVID-19 infections in a number of countries across the globe particularly in Europe.
\nThe outbreak of COVID-19 in China, Asia, and subsequent report of its spread to Europe led many researchers, scientists and policy makers to probe how well the different regions of the world may combat the deadly infectious disease. While there was high hope for the more advanced countries to fiercely fight off COVID-19, owing to the superior healthcare infrastructure in those countries, many wonder how resource-scarce regions will fare in dealing with the pandemic. As expected, many countries put in measures to combat the virus. These included closure of entry points like airports, lockdowns and purchase of personal protective equipment.
\nPer the current death rate data as well as adherence to COVID-19 protocols, Africa may be doing fairly well in the management of the pandemic. The region has one of the lowest COVID-19 death rate (as stated above) and a recovery rate of as high as 85% [17], exceeding the global average rate of 67%. With this appreciable recovery rate, some lessons might be learnt from the management of the pandemic so as to improve healthcare in the region.
\nThe world’s population is projected to witness a huge rise in its ageing index, particularly in developing areas such as Africa [18]. Ageing is associated with increasing probability of proneness to infections due to reduced immune strength. Should these occur without corresponding improvement in healthcare infrastructure and services, there may be dare consequences on the population in these areas in the years ahead. In cases where there are hospitals to admit the aged, in-hospital infection risk needs to be critically checked.
\nAlso, the increasing population of LMICs portends a fertile avenue for the emergence and spread of infections. Infectious diseases account for about half of the total death in Africa [19]. With increasing population implies that inadequate and overcrowded healthcare facilities may serve as vital spreading grounds for infections. Closely related to the increasing population is unplanned and uncoordinated urbanisation in these countries. Due to a number of factors including, predominantly, the burning desire to seek for jobs in the urban and peri-urban areas in these countries, there is bound to be excessive urbanisation. The effect of this was felt in major cities across Africa during the COVID-19 lockdowns initiated in some of these cities. In Accra, Ghana, for example, it was a nightmare providing for most of these people who moved to the cities in search of non-existent jobs hence have no savings to depend on during the brief period of lockdown. If left uncheck, increasing population and its associated urbanisation may pose major obstacles in the fight against emerging and re-emerging infectious diseases in LMICs.
\nThe effect of human-induced global environmental health challenges as evidenced by the problems associated with climate change may be harshly felt by LMICs in the coming years. While these countries may argue that they contribute less to climate change, in comparison to advanced economies, they (LMICs) may severely experience the blunt of climate change-associated problems such as emergence of environmental health conditions owing to their insufficient healthcare resources to combat same. Conversely, the advanced countries have high quality and adequate healthcare infrastructure to, somewhat, more effectively fight off health complications resulting from the changing environmental trends. Low resource settings need to adopt some local, contextualised measures to combat emerging and re-emerging infections in the years ahead.
\nCommunity and traditional leadership can be marshalled to combat some healthcare challenges particularly in remote areas where mainstream healthcare facilities are either lacking completely or highly insufficient. Community mitigation measures have to be initiated and/or intensified through education and awareness campaigns. A large part of the population of many LMICs including Ghana live in remote areas who, due to information gap, do not have a good understanding of developments in relation to many health conditions; just as the emergence of COVID-19 had shown.
\nTo make good use of community involvement in disease prevention and control, effective and efficient community engagement approach needs to be designed and implemented. In particular, key community leaders such as chiefs, assembly and unit committee members/opinion leaders should be involved in the local awareness creation and educational campaigns against diseases. These individuals are well respected in their communities and so would contribute to the dissemination of multilingual, contextually relevant public education and awareness campaign [20]. Where there are Community-based Health Planning and Services (CHPS) centres (mini health centres), the work of the community leaders will complement the activities of the CHPS staff. Also, most villages now have public address platforms where relevant, local information are passed on to residents. This is being used in some places during the COVID-19 pandemic to educate inhabitants. Such awareness creation may be intensified and repeated a number of times on these community platforms. In Kenya, East Africa, for instance, daily broadcast of COVID-19 adverts in local languages in communities were carried out. Central governments should also encourage community-based non-governmental organisations (NGOs) and decentralised governmental institutions located across the various districts to assist in public education on key health issues. This is because these organisations have established good working relationship with their respective communities and so have good understanding and knowledge of the local dynamics hence are able to deliver impactful awareness and education on major health conditions in their catchment areas.
\nWhen it matters most, when the lives of entire communities, cities and countries in some of the world’s poorest places is threatened, ordinary citizens rose to the call. These citizens drew on their inherent ingenuity and devised preventive or protective apparatus against COVID-19. From very simple devices such as a handwashing plastic container with a tap fixed at one side of its lower part, popularly called Veronica bucket in Ghana, mechanised washing devices to solar and electricity powered handwashing apparatus as well as locally-produced digitised thermometer, a number of devices were manufactured within a short space of time during the COVID-19 pandemic. Interestingly, each new device manufactured showed to be an improvement over an existing similar device.
\nSimilarly, many African countries saw the need to increase local productions of personal protective equipment (PPE). Ghana, for example, had unprecedented governmental support for the local textile industry to produce PPE including medical gowns and face masks in large quantities. Hitherto, these PPE are imported from countries such as China. Also, the increased level of technological innovation during the pandemic will be essential if the continent can fight emerging health threats in the future. Since the virus was found to be localised on surfaces including currencies, the predominant cash economies in Africa were at a disadvantage. Technological improvement led to an increasing pace of cashless payments including mobile money payments for public transportation and cost of purchased items. These and other innovative strategies were seen in places such as Ghana, Nigeria and Kenya.
\nGiving the innovative ideas shared and devices produced during the COVID-19 outbreak in many LMICs, it is not far-fetched to suggest that when people feel that their very basic existence as a community or nation is threatened, they are likely to come up with strategies and programmes to ameliorate the supposed daunting challenges. These innovations can be utilised in fighting emerging infectious diseases in many places.
\nCapacity building of the requisite human resource capital is critical if resource-scarce regions of the world will be able to win the war against emerging health threats. The often too inadequate healthcare professionals in these countries can no longer stand the test of time. Healthcare professionals ranging from health promotion officers, public health experts, community health assistants, laboratory technicians, pharmacists, nurses and medical doctors ought to be trained and frequently undergo continuous professional development so as to boost their capacity to effectively tackle health challenges in contemporary times. As has been clearly shown by COVID-19, advanced countries which serve as health tourism destinations for some citizens of LMICs cannot be available for use at certain times since they are also overburdened by cases in their respective countries. It, therefore, implies that elaborate and concerted efforts should be taken, going forward, to boost the capacity of healthcare professionals in LMICs if these countries are to survive the next deadly epidemic or pandemic.
\nEstablishment of a state-of-the-art advanced laboratory alone is not enough. While this is a critical necessity, its maintenance is even more important taking into perspective the lack of maintenance culture in many developing countries. The importance of advanced laboratories in infectious disease prevention and management cannot be overemphasised. Accurate diagnoses and case management are dependent on accurate laboratory investigations. In the same vein, accurate laboratory investigations are obtained from well-equipped, advanced laboratories, with sophisticated equipment. Unfortunately, most countries in LMICs lack the availability of such laboratories. Apart from the need for the establishment of such laboratories, maintenance culture, ironically, in resource-scarce countries is abysmally poor. Ordinarily, one would expect that such countries would rather maintain the few equipment and facilities in their possession. A culture of maintenance needs to be urgently developed in these countries. Standard operating procedures, where they exist, should be strengthen and vigorously followed. In instances where these do not exist presently, strenuous steps should be taken to, as a matter of urgency, put in such protocols. Without this, even should the establishment of advanced laboratories come to fruition, they will not adequately serve the purpose for their establishment. People who default in adhering to the maintenance routine should be penalised severely. This is because refusal to strictly adhere to such practices will result in mass murder in the foreseeable future as those facilities cannot be utilised when they are needed should the next epidemic or pandemic occur.
\nActive involvement of the private sector was seen in the fight against COVID-19. In Ghana, for instance, the private sector and individuals mobilised and built an infectious disease centre, in record time, for the government and people of Ghana. More importantly, this is the first centre wholly built to serve as an infectious disease centre in the country. This is a great initiative that must be modelled, going forward, so as to help strengthen healthcare infrastructure in the country. Likewise, it is an initiative worthy of emulation by other LMICs.
\nAs could be seen from the ongoing pandemic, no one country can successfully fight against a deadly infectious disease. Foreign assistance and careful utilisation of grants/aids and loans obtained from donor agencies and countries must be considered in the development of the healthcare system of LMICs. Unfortunately, misuse and abuse of healthcare support and aids have retarded the development of healthcare system in many of these countries. If countries will make any headway in confronting the challenges posed by emerging health threats in the 21st century, appropriate strategies have to be put in place to curb corruption in the health sector. The abuse of such financial assistance only enriches the few individuals involved but leaves the lives of countless number of people in danger as the intended infrastructure to be built will not see the light of day. Both the receiving country and the donor agency should enhance monitoring measures to ensure effective utilisation of such donations and apply severe sanctions on culprits who will engage in nefarious acts. It is through such means that resources can be put to their intended uses and provide the needed healthcare infrastructure in LMICs enabling the world to prepare and contain emerging infections.
\nMany countries in the global south have instituted health promotion programmes as an integral part of their national health policies. This is a cost-effective approach that can be utilised by resource-constraint countries. Health promotion ensures the adoption and inculcation of appropriate behavioural changes in the population so as to produce desirable results. Health promotion promises to achieve appreciable success in fighting diseases such as malaria and tuberculosis (TB) in Africa.
\nEmerging health threats in Africa such as cardiovascular diseases and obesity whose causes are linked to sedentary lifestyle and associated behavioural tendencies can be fought through extensive and coordinated health promotion approach. With the increasing burden of non-communicable diseases on the continent, health promotion may be instrumental in managing these conditions [3]. The middle class in these countries spend hours unend in their air-conditioned houses, cars and offices with little room for physical exercise. Fast food, rich in calories, in recent years, is a major delicacy for many in some developing countries. Frequent and consistent exercise and change in dietary content, for instance, need to be taken up seriously by the middle class in these countries who due to the nature of their work tend to live sedentary lifestyles. For instance, immune enhancing diet was highlighted by the government and health experts during the peak of COVID-19 in Ghana. This strategy could be used to fight off many infections.
\nOver the years, deadly epidemics and pandemics have originated from human-pathogen contacts [21]. Notably, deadly infectious diseases such as EBOLA virus disease, influenza H1N1 and COVID-19 have been linked to animals such as bat and swine. There is the need for determined efforts by countries to reduce, where appropriate, these possible contacts. Similarly, the increasing change in human-animal ecosystem needs to be checked since this may be an avenue for spread of zoonotic infections.
\nThere might be increasing contacts with hitherto un-encountered animal species. Human-pathogen contacts leading to infections of zoonosis types, for instance, can be reduced if appropriate steps are put in place. It is expedient that governments should institute awareness creation campaigns to educate the populace on the need to avoid excessive contacts of suspected animals. Bushmeat (meat delicacy obtained from wild animals) should be reduced as many of these animals may carry pathogens which may be harmful to human health. Being a major hub of bushmeat, LMICs need to increase surveillance of the consumption of the delicacy so as to reduce zoonotic infectious diseases [18, 19]. Hunters and other persons who may patronise these delicacies should be on the lookout for unusual signs and symptoms so as to quickly report to the hospital should any unknown sign and symptom be seen or felt. These would help prevent or reduce the possibility of getting infected with zoonotic infections in the future.
\nThe fight against emerging and re-emerging infections and diseases needs to be won by all; irrespective of geographical differences. Through the collective efforts of both resource-scarce and advanced countries, appropriate measures could be put in place to strengthen the healthcare system of all countries. This is very necessary to build a resilient international health security owing to the interconnectedness of our world in contemporary times in which an outbreak in the remotest places can in no time reach the busiest of cities with its damning trails. Despite the need for advanced countries and donor agencies to assist resource-constraint regions of the world in building both the human and infrastructural capacity in the less developed countries with the ultimate aim of safeguarding the health of both regions, it is expedient that the less-developed nations draw on the strength of their basic and local potentials, as being exhibited in the COVID-19 fight. The battle against the next possible epidemic or pandemic will be won if and only if individual countries institute appropriate measures (or are assisted to) so as to prevent, detect and contain any future outbreak.
\nNone.
General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed.
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