Malaria: Transmission, Diagnosis, Treatment and Prevention in Indonesia

Abstract

Malaria is a disease caused by Plasmodium and is characterized by recurrent fever, anemia, and hepatosplenomegaly. There are five species of Plasmodium that can infect humans. P. falciparum causes the most deaths, as do P. vivax, P. ovale, and P. malariae which usually cause mild malaria. The aim of this research is to determine the meaning, classification, epidemiology, symptoms, pathogenesis, diagnosis, mode of transmission, prevention, and treatment of malaria. Research method: This research is a descriptive observational study with a literature review design using databases from Google Scholar, accredited national journal Sinta, and reputable international journals such as Scopus, PubMed, Web of Science, and others. The research results show that malaria cases are still high in Indonesia every year. There are several risk factors for malaria such as attitude, behavior, environment, and physical environmental factors where you live, such as (temperature, humidity, livestock pens, houses without screen ventilation, stagnant water, or breeding places). Malaria treatment depends on several factors, including the type of Plasmodium that causes infection, the severity of the disease, and the disease the individual is suffering from. Prevention efforts need to be made by addressing various risk factors for malaria.

1. Introduction

The disease caused by Plasmodium is malaria, which is characterized by recurrent fever, anemia, and hepatosplenomegaly. This disease varies from acute to chronic. During the acute phase, attacks of fever sometimes occur. During subsequent chronic stages, there are latent phases separated at relapse in recent times [1]. Malaria is also a health problem that causes death, especially in high-risk groups such as infants, pregnant women, children under five. Malaria also causes anemia and reduces work [2]. Malaria is an endemic disease in Indonesia and affects all components of the blood. The most common complications are anemia and thrombocytopenia. This is a concern of the scientific literature because it is associated with mortality [3]. Indonesia is a tropical country so that malaria is an infectious disease, especially in some areas which are said to be endemic, especially outside Java, such as Jayapura and others [4].

The type of Plasmodium that causes the infection determines the intensity of the symptoms of malaria. Four species of Plasmodium are known: Plasmodium vivax, is one of the most common infections causing vuvax or tertian malaria or vivax; Plasmodium falciparum, which causes tropical malaria or falciparum malaria, and causes malaria quartana or malriae, nephrotic syndrome and plasmodium ovale which are found in the West Pacific and Africa, resulting in milder outbreaks and frequent outbreaks [5]. There are other species that also cause malaria, that is Plasmodium knowlesi [6]. In severe cases will occur malaria cerebral which also has a fatal impact. Nationally, cases have decreased but are still frequently found throughout Indonesia. This disease requires expertise from an appropriate clinical perspective in determining the diagnosis and therapy in patients. Currently, the management of cerebral malaria in Indonesia is guided by the 2017 Malaria Case Management Book [5].

In many countries around the world, malaria is still a public health problem. Even though the Malaria Implementation and Eradication Program has been started since 1959, the mortality and morbidity rates are still high in this country of Indonesia. Every year, 300 million people are attacked and 2–4 million die. Therefore, the Ministry of Health assesses malaria as a very important problem [1].

In 2010 in Indonesia there were 65% of endemic districts where only about 45% of the population in these districts was at risk of contracting malaria. Based on the results of a community survey during 2007–2010, the prevalence of malaria in Indonesia decreased from 1.39% (Riskesdas 2007) to 0.6% (Riskesdas 2010). Meanwhile, based on reports received during 2000–2009, the malaria morbidity rate tended to decrease, namely 3.62 per 1000 population in 2000 to 1.85 per 1000 population in 2009 and 1.96 in 2010. Meanwhile, the death rate due to malaria reached 1.3% [2, 7].

The national prevalence of malaria based on the 2010 Riskesdas results was 0.6% where provinces with API above the national average were West Nusa Tenggara, Maluku, North Maluku, Central Kalimantan, Bangka Belitung, Riau Islands, Bengkulu, Jambi, Central Sulawesi, Gorontalo and Aceh. The highest prevalence rates were found in eastern Indonesia, namely in West Papua (10.6%), Papua (10.1%) and East Nusa Tenggara (4.4%) [2].

Symptoms that patients show upon their arrival at Manado Central Hospital (now known as Bethesda Omolon Hospital and Prof.dr. R.D.Kandou Hospital. In 1993, malaria cases at Bethesda Tomohon Hospital showed objective symptoms of icterus 3.0%, hepatomegaly 43%, splenomegaly 40.7%, and pallor 6.6%.Other common symptoms are vomiting 31–37%, dizziness 75–82%, nausea 74–76%, chills 64–82%, and fever 92–96% [1].

In North Sulawesi, Indonesia, especially in North Sulawesi Hospitals and Health Centers, malaria itself is a disease that is often found. Malaria infection accounts for 9% of hospitalizations, there are 400 cases of mild malaria and 30–40 cases of severe malaria each year, and 6–7 of them die every year. There is a mortality rate from malaria reaching 15.7% in the most common problems that arise are jaundice and kidney failure in Manado City [1].

In South Jayapura District, Indonesia, it is an endemic area with the third highest malaria rate of the 5 districts in Jayapura city. Malaria cases in Jayapura City in 2019 were 28,648 cases with an API of 92.55/1000 population, in 2020 there were 28,075 cases with an API of 89.35/1000 population, while in 2021 there were 30,235 cases with an API of 99.49/1000 population [8].

However, equipment and human resources still greatly influence how quickly and precisely treatment is provided in city and district hospitals. As of December 2009, only a few hospitals, mainly in Manado and Minahasa, had data on malaria patients [1].

1. Problem Formulation

   1. What is the meaning or definition of malaria?

   2. What is the epidemiology of malaria?

   3. How is malaria classified?

   4. What is the scope of malaria?

   5. What are the symptoms of malaria?

   6. What are the risk factors for malaria

   7. What is the pathogenesis of malaria?

   8. What is the immune response to malaria?

   9. What are the diagnoses for malaria?

   10. What are the modes of transmission of malaria?

   11. What are the ways to prevent malaria?

   12. What are the ways to treat malaria?

2. Objective

   1. To understand the meaning of malaria

   2. To understand the epidemiology of malaria

   3. To understand the classification of malaria

   4. To understand the scope of malaria

   5. To understand the symptoms of malaria

   6. To understand the risk factors for malaria

   7. To understand the pathogenesis of malaria

   8. To understand the immune response to malaria

   9. To understand the diagnosis of malaria

   10. To understand how malaria is transmitted

   11. To understand how to prevent malaria

   12. To understand how to treat malaria

3. Benefit

It is hoped that writing this paper will be useful for readers, especially for people in endemic areas to prevent malaria from occurring. Become a source of scientific literature related to malaria.

2. Methodology

Research method: This research is a descriptive observational study with a literature review design with databases from Google Scholar, Sinta accredited national journals, and reputable international journals such as Scopus, Pubmed, Web of Science and others.

3. Result and discussion

3.1 Definition of malaria

Malaria is an infectious disease caused by the bite of the Anopheles mosquito and Plasmodium parasites. Headache, vomiting, chills, fever, and pain in joints and muscles are symptoms of malaria. If treated properly, certain drugs can cure malaria [9]. Malaria is a disease that attacks humans, birds, monkeys and other primates, reptiles and rodents caused by infection with protozoa of the genus Plasmodium. The incidence or transmission of infectious diseases is determined by risk factors/determinants called host, agent and environment [10].

The main cause of this disease is the female Anopheles mosquito which spreads the infection by biting. Anopheles mosquito bites contain parasites in their saliva which enter the blood of the humans they bite. Parasites migrate to the liver, where they mature and reproduce. There are five species of Plasmodium that infect and can infect humans. P. falciparum causes the most deaths, as do P. vivax, P. ovale and P. malaria usually cause milder forms of malaria. P. knowlesi rarely causes disease in humans. A rapid antigen-based test or a microscopic blood test of a blood sample is usually used to diagnose malaria. Due to cost and complexity, methods for detecting parasite DNA using polymerase chain reactions have not been widely used in areas where malaria is common [9].

3.2 Epidemiology of malaria

Even though there has been a reduction in Annual Parasite Incidence (API) nationally, in areas with high malaria cases the API rate is still very high compared to the national rate, whereas in areas with low malaria cases extraordinary events (KLB) often occur as a result of imported cases. In 2011 the number of reported malaria deaths was 388 case [2].

Information from the World Health Organization (World Health Organization) in 2013 reported that there were 197 million cases of malaria with 548,000 deaths, and 78% of these cases included child deaths under the age of 5 [11]. Furthermore, according to WHO, there were 198 million cases of malaria worldwide in 2014, namely 584. Malaria is widespread in many places around the world, especially in tropical and subtropical regions such as Indonesia. In Indonesia, about 35 percent of the population lives in malaria-prone areas. 584,000 deaths from severe malaria each year. Malaria epidemics occur almost every year in several endemic areas in Indonesia [4]. Areas such as East Nusa Tenggara, West Nusa Tenggara, Maluku, North Maluku, Central Kalimantan, Bangka-Belitung, Riau Islands and Bengkulu are included in the malaria red zone. Next are Jambi, Central Sulawesi, West Sulawesi, Gorontalo and Aceh [4].

Research results related to the prevalence of malaria show that Malaria sufferers were more at the age of 24–35 years, namely as many as 264 sufferers (41.1%), malaria sufferers were more in the female sex as many as 323 people (50.3%), malaria sufferers were more in patients who worked as private employees, namely 410 people (63.9%). More malaria sufferers were found living in urban areas, namely 447 sufferers (69.6%) [12].

Here are some common approaches to treating malaria: Malaria is a disease that is naturally transmitted by pathogens (Plasmodium spp.), definitive hosts (Anopheles spp. and intermediate hosts (humans) [4].

The epidemiological components of malaria consist of: the first pathogen, Plasmodium spp. parasites. Parasites that live in the human body reproduce by consuming red blood cells (RBC), causing anemia in the infected or the host. Second, there are two types of hosts: Humans as intermediate hosts (temporary, because sexual reproduction does not occur) and mosquitoes as definitive hosts (permanent, because sexual reproduction does not occur). Anopheles spp. is a species of mosquito that transmits malaria. However, not all species causes malaria. Plasmodium is spread by malaria, which is bitten by a mosquito (carrier) and then enters the carrier’s body via blood cells in various asexual stages. Endemic malaria [4].

3.3 Classification of malaria

Malaria is an infectious disease caused by Plasmodium parasites which can be characterized by fever, hepatosplenomegaly, and anemia. Plasmodium lives and reproduces in human red blood cells. This disease is naturally transmitted through the bite of a female Anopheles mosquito.

Plasmodium species in humans are:

1. Plasmodium falciparum (P. falciparum).

2. Plasmodium vivax (P. vivax)

3. Plasmodium ovale (P. ovale)

4. Plasmodium malariae (P. malariae)

5. Plasmodium knowlesi (P. knowlesi)

The most common types of Plasmodium found in Indonesia are P. falciparum and P. vivax, while P. malariae can be found in several provinces, including Lampung, East Nusa Tenggara, and Papua. P ovale has been found in East Nusa Tenggara and Papua. In 2010 on the island of Borneo it was reported that P. knowlesi could infect humans where previously it only infected primates/monkeys and until now [2].

According to Harijanto [13], Malaria is further divided according to its Plasmodium type, including:

3.3.1 Plasmodium falciparum (tropical malaria)

Tropical malaria, also known as tropical falciparum malaria, is the most severe form of malaria. This disease is characterized by anemia, fever, blood parasites, and splenomegaly, often causing complications. The disease lasts 9–14 days. Tropical malaria affects all types of red blood cells caused by Plasmodium falciparum. The only Plasmodium species with duplicated nuclear chromatin in the form of a ring or small rings one-third the diameter of a normal red cell. Spread of tropical malaria is classified when Plasmodium falciparum infects red cells for life, often resulting in the formation of blood cell parasites that produce multiple protrusions that can adhere to the endothelial lining of capillary walls due to thrombotic occlusion and local ischemia. This infection is more serious than other infections and causes many complications such as cerebral malaria, gastrointestinal disorders and black hemorrhagic fever.

3.3.2 Plasmodium malariae (Kwartama malaria)

Tropozoites of Plasmodium malariae which are smaller than Plasmodium vivax have more compact or bluer cytoplasm. Mature trophozoites have dark brown to black grains and are often grouped in groups.

3.3.3 Plasmodium ovale (malaria ovale)

Malaria ovale, known as Plasmodium ovale, is similar in shape to Plasmodium malariae, but the schizont consists of only eight merozoites and has a black mass in the center. Red blood cells infected with Plasmodium ovale are usually oval or irregular in shape with a visible ciliated pattern. Of all the types of malaria caused by Plasmodium ovale, malaria ovale is the mildest. The incubation period varies from 11 to 16 days, but the latent period can be up to 4 years. Attacks last 3 to 4 days without treatment, rarely more than 10 days, and occur at night.

3.3.4 Plasmodium vivax (tertian malaria)

Plasmodium vivax infection, or tertian malaria, can sometimes affect the young red blood cells, which are larger than normal red blood cells. It resembles Plasmodium falciparum in appearance, but vivax trophozoites become amoebae with age. Consists of 12–24 oval merozoites with yellow pigment at the poles. Oval gametocytes occupy almost all of the red blood cells, eccentric chromatin and yellow pigment. Symptoms of this type of malaria last 48 hours as shown in the malaria triad, causing intermittent fever every 4 days, with a peak of fever occurring every 72 hours. Of all the Plasmodium and malaria species that invade the body, tropical malaria is the most important. It is manifested by unstable fever, anemia, splenomegaly, multiple parasites and frequent complications [13].

3.4 Scope malaria

Malaria is a disease in the world, especially in tropical and subtropical regions, the cause of which is the Plasmodium parasite, which is transmitted through the bite of the Anopheles mosquito [14].

The scope of malaria covers several important aspects, including:

1. Geographical breakdown: of 100 countries worldwide, mainly in sub-Saharan Africa, Latin America and parts of Asia. The region where malaria is most common is Africa where malaria is endemic.

2. The Anopheles mosquito is the main cause of malaria. They bite an infected person and then transmit the Plasmodium parasite to other people when they bite.

3. Causes and Types of Parasites: Five different types of Plasmodium cause malaria: Plasmodium malariae, Plasmodium vivax, Plasmodium ovale, Plasmodium falciparum, Plasmodium knowlesi is the main cause of malaria, the most dangerous of all.

4. Clinical Symptoms: Symptoms of malaria include fever, chills, severe headache, nausea, vomiting and fatigue. If left untreated, malaria can become a life-threatening disease. Prevention: Prevention of malaria involves controlling mosquito vectors through use of insecticide-treated nets, use of antimalarial drugs for prophylaxis, administration of vaccines (such as RTS, S vaccine), and use of mosquito bite prevention measures such as anti-mosquito lotions and repellents

5. Diagnostics and treatment: Diagnosis of malaria involves microscopic examination of blood for the detection of Plasmodium parasites or use of an antigen-based rapid malaria test. Treatment depends on the type of Plasmodium causing the infection and the severity of the disease. Effective antimalarial drugs such as artemisinin-based combination therapy (ACT) are used to treat malaria infection.

6. Social and economic impacts: Malaria has significant social and economic impacts, especially in areas with a high prevalence. Malaria can cause school and work absences, reduced productivity, and a large economic burden on individuals and communities. Tackling the malaria problem requires a comprehensive approach, including vector prevention, effective treatment, access to diagnosis and treatment, and research for the development of more effective vaccines. Global efforts such as vector control campaigns, distribution of insecticide-treated nets, and vaccination initiatives have helped reduce the global burden of malaria. Significant.

7. Genetic Aspects of Malaria: Several genetic factors are the main determinants for child survival in malaria endemic countries. Identification of the genes involved and how they affect the risk of malaria can provide a mechanism for studying the host-parasite relationship. Several gene polymorphisms associated with malaria are Human Red Blood Cell Polymorphisms [15].

3.5 Symptoms of malaria

Manifestations of malaria are fever, anemia and enlargement of the spleen [16].

In people who have been taking antimalarial drugs for prevention, symptoms of malaria may appear later, usually 8 to 25 days after infection. In all types of malaria, the illness is generally flu-like and can mimic sepsis, gastroenteritis, and viruses. Symptoms include: Headache, fever and chills, arthralgia, vomiting, hemolytic anemia, jaundice, urinary hemoglobin, retinal damage and seizures. The main symptoms of malaria are paroxysmal symptoms, including cyclic fever and persistent chills. Then infection with P. vivax and P. ovale on the second day, called tertiary fever, and every third day, called quarantine fever, with P. falciparum can cause recurring fever every 36 to 48 hours or less. One, almost constant fever. Plasmodium falciparum, commonly called falciparum malaria, is the main cause of severe malaria. Symptoms of falciparum malaria appear 9 to 30 days after infection. Neurologic symptoms such as nystagmus, postural disturbances, opisthotonos, seizures or coma are common in individuals with cerebral malaria [17].

3.6 Risk factors of malaria

3.6.1 Characteristics of the physical environment

Based on the results of the research that has been carried out, factors that can occur are caused by the roof/wall of the house that is not tightly closed due to the type of wall made of boards or plywood, there is no ceiling, the ventilation of the house does not use gauze, there is a pool of water or breeding place such as (gutters, ponds and swamps) as well as houses close to resting place or bushes. The factors that have been described will result in the presence of Anopheles sp. mosquitoes if not immediately addressed and corrected.

3.6.2 Behavioral characteristics

Lack of public knowledge about the importance of preventing malaria in their environment and lack of support for malaria cases. It can be concluded that the factors that cause malaria are related to the individual’s lack of concern for the environment around his home. Physical environment variables such as the density of the walls of the house, the screens on the ventilation, and the ceilings of the house haverelationship with malaria incidence. In addition, behavioral variables such as actions also play a role in the spread of the disease.

To reduce the risk of malaria, people are expected to keep their homes free of mosquitoes by installing tight walls, ceilings and screens for ventilation. In addition, they expect more attention to the environment around the house by adopting environmental management practices, that is, H. save, empty, clean and empty clogged drains and trim bushes.

Malaria control efforts involve environmental management, prevention of mosquito bites, treatment of infected cases, as well as education and community participation. This aims to reduce the presence of mosquito vectors and stop the Plasmodium transmission cycle in the human population [8].

3.7 Pathogenesis of malaria

The rupture of the blood schizont is caused by the release of several antigens and can cause fever in the body. Macrophage cells, monocytes and lymphocytes can be stimulated by antigens to release cytokine types including Tumor Necrosis Factor. And IL-6 V then enters the hypothalamus, the body’s temperature control center. In the four plasmodia it takes a different time for sizogony [2, 18].

Excessive destruction of red blood cells in the malaria parasite is the cause of decreased hemoglobin values, and anemia also occurs due to disturbances in the spinal cord in forming red blood cell [19]. As a result of hemolysis, there is sequestration of erythrocytes in the spleen and other organs, and depression in the bone marrow [16]. In severe cases, cerebral malaria will occur in a febrile patient with decreased consciousness [5]. Cerebral malaria is an acute encephalopathy that meets three criteria, namely coma that cannot be awakened, or coma that persists for >30 minutes after the seizure and is accompanied by P. falciparum indicated by a blood smear [20].

Infected or uninfected red blood cells are damaged, causing anemia. Plasmodium ovale and Plasmodium vivax infect immature erythrocytes, making up 2% of total erythrocytes, and P. malariae only infects mature erythrocytes, making up 1% of total erythrocytes. All types of red blood cells are infected with Plasmodium falciparum, so anemia can occur in both acute and chronic infections. Plasmodium lesions are caused by splenic macrophages and lymphocytes, which are reticular endothelial cells. These inflammatory cells enlarge the spleen. Malignant malaria caused by P. falciparum has a unique pathogenesis. Once infected with P. falciparum, the parasite’s red blood cells spread through the capillaries of the body’s organs. In addition, the bumps that form on the surface of infected red blood cells contain various P. falciparum antigens. Cytokines such as TNF and IL-6, produced by macrophages, monocytes and lymphocytes, activate capillary endothelial cell receptor expression. Cell adhesion occurs when nodules attach to endothelial cell receptors in capillaries. This process causes tissue ischemia due to capillary occlusion. The “asterisk” method - clustering - also supports this inhibition (Figure 1) [22].

Figure 1.

Plasmodium life cycle in general [21].

3.8 Immune response against malaria

The immune response to malaria infection involves a number of complex mechanisms. When the malaria parasite (Plasmodium) enters the human body through the bite of a vector mosquito, the body’s immune system will respond to fight the infection. Following are some of the important stages in the immune response to malaria:

1. Initial stage: After the parasites enter the body, they will enter the liver and reproduce there. During this stage, the initial immune response will involve immune cells such as macrophages and dendritic cells that recognize the parasite and respond by secreting immune-stimulating molecules such as cytokines.

2. Erythrocyte phase: After leaving the liver, the parasite enters red blood cells (erythrocytes) and multiplies there. At this stage, the parasite changes shape and secretes waste products that can trigger an immune response.

3. T cell response: In the fight against malaria infection, T cells, also known as cytotoxic T cells and helper T cells, play an important role. They can recognize parasitic proteins on the surface of infected red blood cells and then act by killing those cells or sending signals to trigger a new immune response.

4. Antibody response: The immune system also produces antibodies to fight parasites. Antibodies are proteins made by plasma cells that can bind to parasites and destroy them, helping to stop them from growing and preventing them from invading more red blood cells.

5. Inflammation: Malaria infection often causes systemic inflammation involving the release of cytokines and other inflammatory molecules. This can cause malaria symptoms such as fever, aches, and malaise.

It is important to note that Plasmodium has the ability to evade or trick the human immune system by changing their protein surface on a regular basis. This allows them to evade detection by the immune system and makes it difficult to develop an effective immune response.

The immune response to malaria can be complex and varies depending on the type of parasite, individual immunity, and other factors. Because of this complexity the development of an effective vaccine for malaria has become a significant challenge in the management of this disease. However, research and efforts are continuing to understand the mechanisms of the immune response and develop effective vaccination strategies [15, 23].

3.9 Diagnosis of malaria

In areas where malaria is rare, the diagnosis of malaria requires a high degree of suspicion, which can be triggered by:

1. Recent travel notes

2. The spleen develops

3. fever

4. Low platelet count

5. Higher than normal blood bilirubin levels in combination with a normal white blood cell count.

Blood smear microscopy or rapid antigen-based test (RDT) is often used to confirm the diagnosis of malaria. In 2010, approximately 165 million meninges were tested for malaria, and microscopy is the most commonly used method of identifying malaria parasites. Despite its widespread use, microscopy has two major drawbacks [2].

In border areas, many testing facilities are not well equipped and the accuracy of results depends on the performance of blood membrane testing kits and the number of parasites in the blood. The sensitivity of blood samples varies between 75 and 90°, up to 50% under optimal conditions. Commercially available RDTs are often more accurate than blood films in predicting the presence of malaria parasites, but their diagnostic sensitivity and specificity vary widely between manufacturers and cannot be determined. Any healthy person who has traveled to a malaria endemic area should be suspected of having malaria and examined where tests are available. In places where laboratory diagnostic tests cannot be performed, the use of pre-existing fever as an indication for treatment of malaria has become widespread. As a result, the popular notion that “fever is synonymous with malaria if proven otherwise” has spread. Malaria over diagnosis and poor non-malarial therapy limit this approach, consume limited resources, reduce trust in the health system and increase drug resistance. Although assays that rely on polymerase chain reaction have been developed, their complexity has prevented their widespread use in areas where malaria is common. Increased resistance to polymerase chains has been developed, but because of its complexity it is not widespread in areas where malaria is common [2].

3.10 Transmission of malaria

The determinants of malaria transmission are divided into two broad categories. First, the factors that have a direct effect, the average mosquito bites humans in a day, the average Plasmodium gametocytes in the population, the length of the sporogonic cycle in the mosquito’s body, the average daily survival rate of mosquitoes. Second, indirect factors, including environment and climate, rainfall, drought, management of the artificial environment, changes in vector biting patterns, air temperature, humidity, importation of malaria parasites through population movements and migration of non-immune populations [24].

One of the ways that malaria can be transmitted is by the bite of a vector mosquito infected with Plasmodium. Here are some ways of transmitting malaria:

1. Anopheles mosquito bites: The main cause of malaria is the bite of the Anopheles mosquito. When a mosquito bites a person infected with malaria, Plasmodium in their blood can enter the mosquito’s body. When the mosquito bites another person, Plasmodium infects the person bitten and causes a malaria infection.

2. Blood transfusion: In rare cases, malaria can also be transmitted by blood transfusion. When a person with malaria donates blood, Plasmodium in the blood can infect the recipient.

3. The use of syringes that are contaminated with blood containing Plasmodium can also be a source of malaria transmission. This can happen if needles are used simultaneously by people infected with malaria and other people without adequate sterilization procedures.

4. Perinatal Transmission: It is possible for malaria to be transmitted from a pregnant woman who is infected with malaria to her baby during pregnancy or childbirth. This is known as perinatal transmission [4].

3.11 Prevention of malaria

Efforts to eradicate malaria in Indonesia have not achieved optimal results due to several factors such as the prevalence of malaria mosquitoes, the high number of cases, human resources, costs and infrastructure. Therefore, the best course of action is to prevent and stop the spread of the parasite. Many efforts can be made to prevent and eradicate the spread of malaria parasite [25].

Methods for preventing mosquito bites are particularly important in high prevalence areas. It is recommended to wear long sleeves and long pants when going out, especially at night, in rural or suburban areas with lots of rice fields, swamps or fish ponds (ideal breeding grounds for malaria-carrying mosquitoes).

Efforts to reduce morbidity and mortality are carried out through a malaria eradication program whose activities include early diagnosis, prompt and appropriate treatment, and vector surveillance and control in terms of public education and understanding of environmental health, all of which are aimed at breaking the chain of malaria transmission.

Resistance cases of malaria parasites to chloroquine were first discovered in East Kalimantan in 1973 for P. falciparum, and in 1991 for P. vivax in Nias. Since 1990, cases of resistance have been reported to have spread in all provinces in Indonesia. In addition, there have also been reports of resistance to Sulfadoxine-pyrimethamine (SP) in several places in Indonesia. This situation can increase the morbidity and mortality of malaria. Therefore, to overcome this problem of resistance (multiple drug resistance) and the existence of new anti-malarial drugs that are more patent, the government has recommended drugs of choice to replace chloroquine and SP, namely a combination of artemisinin derivatives with other anti-malarial drugs which are commonly referred to as Artemisinin based [2].

3.12 Treatment of malaria

Treatment of malaria depends on several factors, including the type of Plasmodium causing the infection, the severity of the disease, and the individual’s health condition [9].

1. Antimalarial drugs: Antimalarial drug therapy is the main step in the treatment of malaria. Several types of drugs are used including:

   • Artemisinin-based combination therapy (ACT) This is the standard treatment for malaria caused by Plasmodium falciparum. ACT combines artemisinin compounds with other antimalarial drugs to treat infections.

   • Chloroquine: Chloroquine is usually used to treat malaria caused by Plasmodium malariae, Plasmodium vivax and Plasmodium ovale. However, many areas of the world report resistance to chloroquine, limiting its use. Other drugs: There are other antimalarial drugs used in the treatment of malaria, such as mefloquine, doxycycline, atovaquone/proguanil, and kinin. The choice of drug depends on the type of Plasmodium and the level of resistance in the affected area [26].

2. Supportive therapy. In severe cases of malaria, supportive therapy may be required. This involves monitoring and managing symptoms such as high fever, dehydration, electrolyte disturbances, anemia, and organ dysfunction. In some cases, hospitalization may be required for more intensive monitoring and adequate treatment.

3. Prevention of complications: Malaria can cause serious complications, such as severe anemia, respiratory problems, kidney failure and neurological disorders. Prevention and treatment of these complications is also an important part of malaria management.

It is important to note that antimalarial drug resistance is becoming an increasingly serious problem in some areas. Therefore, it is important to follow medication recommendations and consult a doctor who is experienced in treating malaria. In addition to treatment, prevention of malaria is essential, including the use of insecticide-treated nets and the prophylactic use of antimalarial drugs for those living in or traveling to remote areas. Use of mosquito repellents and control of mosquito vectors through eradication programs or the use of chemical insecticides (Table 1) [9].

No	Researcher	Research title	Results	Discussion
1	Ragil Setiabudi, [27]	Systematic Review: Risk of Malaria as an Infectious Disease in Indonesia	Based on the similarity of variables between researchers, there are 21 significant risk factors statistically, namely the presence of mosquito breeding places, without screens/barriers on ventilation of the house, not using mosquito coils, presence of bushes, presence of puddles water, presence of paddy fields, presence of ditches/gutches, presence of animal cages, poor housekeeping, house walls not tight, no ceiling, construction of non-permanent house floors, frequent activities outside the home at night, not using mosquito nets when sleeping, hanging clothes in the house, not using pesticides/insecticides, not using mosquito repellant/topical repellant, low education, income below the minimum wage, non-compliance with taking medication, malnutrition status with an average OR = 5.30. Minimum value OR = 0.26 and maximum value OR = 16.92. There are only two protective factors, namely frequent using mosquito nets on the bed (OR = 0.26) and having a ceiling (OR = 0.69).	Risk factors for malaria incidence in Indonesia which means statistically there are 21 namely the presence of mosquito breeding places, without gauze/barrier on ventilation house, do not use mosquito coils, the presence of bushes, the presence of standing water, there are rice fields, there are ditches/ditches, existence of animal cages, cleanliness bad house, the walls of the house are not tight, no ceiling house, construction house floors are not permanent, often outdoor activities at night did not use mosquito nets at the time sleep, hang clothes inside house, do not use pesticides/insecticides, do not use repellant/repellent topical medication mosquitoes, primary education, income in below the minimum wage, non-compliance taking medication, poor nutritional status.; The average OR for the incidence of Malaria is 5.30 The protective factor for the occurrence of Malaria is the frequent use of mosquito nets on the bed and the presence of a ceiling
2	Utami, Tya Palpera; Hasyim, Hamzah; Kaltsum, Ummi; Dwifitri, Uthu; Meriwati, Yanti; Yuniwarti, Yuniwarti; Paridah, Yusro; Zulaiha, Zulaiha [28]	Risk Factors Causing Malaria in Indonesia: Literature Review	Malaria is still a disease with high cases in Indonesia for everyone the year. Factors that cause malaria in Indonesia consist of factors people’s behavior and attitudes (nighttime activities, use of anti-inflammatory drugs) mosquitoes and use of mosquito nets), environmental factors and the physical environment place of residence (presence of livestock pens, presence of bushes, presence of watery rice fields, temperature, humidity, presence of wires on ventilation, the condition of the ceiling of the residence, and the density of the walls of the house). One of ways to prevent and combat malaria by increasing individual and environmental sanitation.	Community behavior and attitudes; Public awareness can be seen from the preventive measures taken such as [1] The habit of staying out late at night, [2] Carrying out environmental health activities, [3] Using mosquito nets. The purpose of using mosquito nets while sleeping is to limit mosquitoes that are infected with bite healthy people and healthy mosquitoes bite sick people, [4] Using household mosquito repellents. Household insecticides are anti-mosquito products that are often used by the community, such as mosquito coils and anti-mosquito sprays [5] Use of mosquito repellents [6]. Use of Body Cover, [7] Installation of Gauze Wire on window doors to prevent mosquitoes from entering the house; Environmental factor; Physical environmental factors of the house (temperature, humidity, the presence of wires on the ventilation, the existence of the ceiling of the house, and the density of the walls of the house). The spread of malaria depends on the interaction between the carrier agent, the host and the environment. The environment that plays a role in the bionomic development of mosquitoes is the physical environment and the biological environment.; The environment has a major influence on the incidence of malaria. The existence of brackish water lakes, stagnant water in forests, rice fields, fish ponds, clearing of forests and mining in an area will increase because these places are places where malaria mosquitoes spread.
3	Suwito; Hadi, Upik Kesumawati; Sigit, Singgih H; Sukowati, Dan Supratman [29]	Climate Relations,; Density; Anopheles mosquito; and Genesis; Malaria disease	A. sundaicus mosquito is a type of mosquito that is influential in; Rajabasa Subdistrict and Weather Mirror Field have no relationship means the number of Anopheles mosquitoes.	The Rajabasa sub-district found 10 species of Anopheles that came into contact with humans, namely A. sundaicus, A. vagus, A. tessellatus, A. aconitus, A. subpictus, A. annularis, A. kochi, A. minimus, A. barbirostris and A. maculatus. The Padangcermin sub-district found eight species of Anopheles that came into contact with humans, namely A. sundaicus, A. subpictus, A. barbirostris, A. kochi, A. aconitus, A. tessellatus, A. vagus and A. hyrcanus group. The A. sundaicus mosquito is the dominant species in Rajabasa and Padang-mirror sub-districts, as shown by the very high number of bites per person per hour (MHD) compared to other species.; The increase in air humidity and rainfall is directly proportional to the increase in mosquito density. Rainfall has a significant relationship with mosquito density; Anopheles, while the density of Anopheles mosquitoes has a significant relationship with malaria cases 1 month later.
4	Permadani, Yudea; Patungo, Viertianingsih; Nompo, R [30]	literature Review: Community Behavior in Malaria Prevention	Research result This literature shows that the level of knowledge, the attitudes and actions of the community in the prevention of malaria are still low so that it affects the low malaria prevention behavior such as the use of mosquito nets in the community and use of mosquito repellents and installation of wire netting on house ventilation.; Public awareness in preventing malaria is shown in behavior community through keeping the environment clean, insecticide-treated mosquito nets, wire netting on ventilation houses, counseling health workers and the use of anti-mosquito drugs. This behavior delivers	Environmental hygiene; The environment is very important in the prevention of malaria. The areas where people live mostly have bushes around the house, some people also live near rivers where there is still a lot of plastic waste scattered which causes mosquitoes to breed. The existence of malaria mosquitoes in an area is very dependent on the environment, where they are often found mosquito breeding around terraced rice fields and irrigation canals.; Another effort is to do 3 M (draining, closing and burying) Draining is cleaning a place that is often used as a water reservoir such as a bathtub, water bucket, drinking water reservoir, refrigerator water reservoir and others.; Wire mesh on house ventilation; Installation of wire netting in the ventilation holes of the house is one step to limit the entry of malaria-transmitting mosquitoes into the house.; Mosquito repellent; The most widely used types of mosquito repellents are the types of mosquito coils and anti-mosquito lotions. People who are used to using mosquito repellents while sleeping or outside the home are aware of the dangers of malaria; Health worker education; Apart from installing ventilation screens at home, health workers very rarely conduct counseling so that not much information is obtained by the community about the incidence of malaria
5.	Fitriani Kahar, Djoko Priyatno, Beatrix Marta Meo [31]	Study Of Erythrocyte Index In Malaria Positive Diagnosis Patients	Research on examining the value of the erythrocyte index in patients with a positive diagnosis of malaria using the manual method can be concluded that there is an MCV that is less than normal is 50%, normal is 50% and which is more than normal is 0%. MCH less than is 35%, normal 65%, and more than normal 0%. MCHC that is less than normal and more than normal is 0% while the normal is 100%.	In addition, a definite diagnosis of malaria is by microscopic examination and finding malaria parasites in the blood and supported by clinical symptoms in patients. On positive patient blood smears malaria, visible differences in blood cells red and forms of the malaria parasite. Next, check the quantity erythrocyte and hematocrit values. Malaria infection is one of the main infectious diseases that occur in the world that causes infection in humans; humans with fever periodic occurrence of fever due to infection from malaria parasites (including protozoa) transmitted by Anopheles mosquitoes.; Manifestations of malaria are fever, anemia and spleen enlargement.; The life cycle of the parasite takes place in humans and in mosquitoes.

Table 1.

Table of literature research results.

4. Conclusions

Tackling the malaria problem requires a comprehensive approach that includes vector prevention, effective treatment, access to diagnosis and treatment, and research to develop more effective vaccines. Global efforts such as vector control campaigns, distribution of insecticide-treated bed nets and vaccination initiatives have helped reduce the global burden of malaria.

There are several risk factors for the occurrence of malaria such as attitudes, behavior, environment and physical environmental factors of residence such as (temperature, humidity, presence of cattle pens, the house is not ventilated through gauze, there are stagnant water or breeding grounds. Treatment of Malaria Treatment of malaria depends on several factors, including the type of Plasmodium that causes the infection, the severity of the disease and the individual’s illness. It is necessary to carry out prevention efforts by addressing various risk factors for malaria to prevent cases of malaria. One way to prevent and overcome malaria is to improve individual and environmental sanitation.

Acknowledgments

Thank you to the Poltekkes Kemenkes Semarang who have contributed invaluable in writing this scientific paper, and to the team that has assisted in collecting data in this study.

Conflict of interest

No conflicts of interest are disclosed by the authors.

Funding

Nil.

Notes/thanks/other declarations

The concept of this paper was developed by F.K, Y.S, S.Y.D.W, D.A, and NQ, who also wrote the script. The final manuscript submitted has been read and approved by all authors.