Malaria
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Malaria is a mosquito-borne infectious disease that affects vertebrates and Anopheles mosquitoes.<ref name="www.who.int-2">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref><ref name="WHO-2014" /> Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches.<ref name="Caraballo-2014" /><ref>Template:Cite journal</ref> In severe cases, it can cause jaundice, seizures, coma, or death.<ref name="Caraballo-2014" /><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito.<ref name="www.who.int-4">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="US CDC-2023" /> If not properly treated, people may have recurrences of the disease months later.<ref name="WHO-2014" /> In those who have recently survived an infection, reinfection usually causes milder symptoms.<ref name="Caraballo-2014" /> This partial resistance disappears over months to years if the person has no continuing exposure to malaria.<ref name="Caraballo-2014">Template:Cite journal</ref> The mosquitoes themselves are harmed by malaria, causing reduced lifespans in those infected by it.<ref>Template:Cite journal</ref>
Malaria is caused by single-celled microorganisms of the genus Plasmodium.<ref name="www.who.int-4" /> It is spread exclusively through bites of infected female Anopheles mosquitoes.<ref name="www.who.int-4" /><ref>Template:Cite journal</ref> The mosquito bite introduces the parasites from the mosquito's saliva into the blood.<ref name="WHO-2014" /> The parasites travel to the liver, where they mature and reproduce.<ref name="Caraballo-2014" /> Five species of Plasmodium commonly infect humans.<ref name="www.who.int-4" /> The three species associated with more severe cases are P. falciparum (which is responsible for the vast majority of malaria deaths), P. vivax, and P. knowlesi (a simian malaria that spills over into thousands of people a year).<ref name="WHO">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> P. ovale and P. malariae generally cause a milder form of malaria.<ref name="Caraballo-2014" /><ref name="www.who.int-4" /> Malaria is typically diagnosed by the microscopic examination of blood using blood films, or with antigen-based rapid diagnostic tests.<ref name="Caraballo-2014" /> Methods that use the polymerase chain reaction to detect the parasite's DNA have been developed, but they are not widely used in areas where malaria is common, due to their cost and complexity.<ref name="Nadjm-2012">Template:Cite journal</ref>
The risk of disease can be reduced by preventing mosquito bites through the use of mosquito nets and insect repellents or with mosquito-control measures such as spraying insecticides and draining standing water.<ref name="Caraballo-2014" /> Several medications are available to prevent malaria for travellers in areas where the disease is common.<ref name="WHO-2014" /> Occasional doses of the combination medication sulfadoxine/pyrimethamine are recommended in infants and after the first trimester of pregnancy in areas with high rates of malaria.<ref name="WHO-2014" /> As of 2023, two malaria vaccines have been endorsed by the World Health Organization.<ref name="WHO recommends R21-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The recommended treatment for malaria is a combination of antimalarial medications that includes artemisinin.<ref name="Rawat-2021">Template:Cite journal</ref>Template:Sfn<ref name="Caraballo-2014" /><ref name="WHO-2014" /> The second medication may be either mefloquine (noting first its potential toxicity and the possibility of death), lumefantrine, or sulfadoxine/pyrimethamine.<ref name="World Health Organization-2010">Template:Cite book</ref> Quinine, along with doxycycline, may be used if artemisinin is not available.<ref name="World Health Organization-2010" /> In areas where the disease is common, malaria should be confirmed if possible before treatment is started due to concerns of increasing drug resistance.<ref name="WHO-2014" /> Resistance among the parasites has developed to several antimalarial medications; for example, chloroquine-resistant P. falciparum has spread to most malaria-prone areas, and resistance to artemisinin has become a problem in some parts of Southeast Asia.<ref name="WHO-2014">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
The disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator.<ref>Template:Cite book</ref><ref name="Caraballo-2014" /> This includes much of sub-Saharan Africa, Asia, and Latin America.<ref name="WHO-2014" /> In 2023, some 263 million cases of malaria worldwide resulted in an estimated 597,000 deaths.<ref name="Daily 2025" /> Around 95% of the cases and deaths occurred in sub-Saharan Africa. Rates of disease decreased from 2010 to 2014, but increased from 2015 to 2021.Template:Sfn According to UNICEF, nearly every minute, a child under five died of malaria in 2021,<ref name="UNICEF DATA-2">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and "many of these deaths are preventable and treatable".<ref name="UNICEF-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Malaria is commonly associated with poverty and has a significant negative effect on economic development.<ref name="Gollin-2007" /><ref name="Worrall-2005" /> In Africa, it is estimated to result in losses of US$12 billion a year due to increased healthcare costs, lost ability to work, and adverse effects on tourism.<ref name="Greenwood-2005" /> The malaria caseload in India was slashed by 69 per cent from 6.4 million (64 lakh) in 2017 to two million (20 lakh) in 2023. Similarly, the estimated malaria deaths decreased from 11,100 to 3,500 (a 68-per cent decrease) in the same period.<ref>Template:Cite news</ref>
EtymologyEdit
The term malaria originates from Medieval Template:Langx 'bad air', a part of miasma theory; the disease was formerly called ague or marsh fever due to its association with swamps and marshland.<ref>Template:Cite journal</ref> The term appeared in English at least as early as 1768.<ref>Template:Cite book</ref> Malaria was once common in most of Europe and North America,<ref name="Lindemann-1999" /> where it is no longer endemic,<ref name="Gratz-2006" /> though imported cases do occur.Template:Sfn The scientific study of malaria is called malariology.<ref>“Malariology.” Merriam-Webster.com Dictionary, Merriam-Webster, https://www.merriam-webster.com/dictionary/malariology. Accessed 18 Nov. 2024.</ref>
Signs and symptomsEdit
Adults with malaria tend to experience chills and fever—classically in periodic intense bouts lasting around six hours, followed by a period of sweating and fever relief—as well as headache, fatigue, abdominal discomfort, and muscle pain.<ref name="Despommier-2019">Template:Cite book</ref> Children tend to have more general symptoms: fever, cough, vomiting, and diarrhea.<ref name="Despommier-2019" />
Initial manifestations of the disease—common to infection with all malaria parasite species—are similar to flu-like symptoms,<ref name="Bartoloni-2012" /> and can resemble other conditions such as sepsis, gastroenteritis, and viral diseases.<ref name="Nadjm-2012" /> The presentation may include headache, fever, shivering, joint pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage, and convulsions.<ref name="Beare-2006" />
The classic symptom of malaria is paroxysm—a cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days (tertian fever) in P. vivax and P. ovale infections, and every three days (quartan fever) for P. malariae. P. falciparum infection can cause recurrent fever every 36–48 hours, or a less pronounced and almost continuous fever.<ref name="Ferri-2009" />
Symptoms typically begin 10–15 days after the initial mosquito bite, but can occur as late as several months after infection with some P. vivax strains.<ref name="Despommier-2019" /> Travellers taking preventative malaria medications may develop symptoms once they stop taking the drugs.<ref name="Despommier-2019" />
Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection.<ref name="Bartoloni-2012" /> Individuals with cerebral malaria frequently exhibit neurological symptoms, including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the eyes to turn together in the same direction), opisthotonus, seizures, or coma.<ref name="Bartoloni-2012" />
ComplicationsEdit
Malaria has several serious complications, including the development of respiratory distress, which occurs in up to 25% of adults and 40% of children with severe P. falciparum malaria. Possible causes include respiratory compensation of metabolic acidosis, noncardiogenic pulmonary oedema, concomitant pneumonia, and severe anaemia. Although rare in young children with severe malaria, acute respiratory distress syndrome occurs in 5–25% of adults and up to 29% of pregnant women.<ref name="Taylor-2012" /> Coinfection of HIV with malaria increases mortality.<ref name="Korenromp-2005" /> Kidney failure is a feature of blackwater fever, where haemoglobin from lysed red blood cells leaks into the urine.<ref name="Bartoloni-2012" />
Infection with P. falciparum may result in cerebral malaria, a form of severe malaria that involves encephalopathy. It is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever.<ref name="Beare-2011" /> An enlarged spleen, enlarged liver or both of these, severe headache, low blood sugar, and haemoglobin in the urine with kidney failure may occur.<ref name="Bartoloni-2012" /> Complications may include spontaneous bleeding, coagulopathy, and shock.<ref>Davidson's Principles and Practice of Medicine/21st/351</ref>
Cerebral malaria can bring about death within forty-eight hours of the first symptoms of the infection being evident.
Malaria during pregnancy can cause stillbirths, infant mortality, miscarriage, and low birth weight,<ref name="Hartman-2010" /> particularly in P. falciparum infection, but also with P. vivax.<ref name="Rijken-2012" />
CauseEdit
Malaria is caused by infection with parasites in the genus Plasmodium.<ref name="US CDC-2022">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In humans, malaria is caused by six Plasmodium species: P. falciparum, P. malariae, P. ovale curtisi, P. ovale wallikeri, P. vivax and P. knowlesi.<ref name="Ashley-2018">Template:Cite journal</ref> Among those infected, P. falciparum is the most common species identified (~75%) followed by P. vivax (~20%).<ref name="Nadjm-2012" /> Although P. falciparum traditionally accounts for the majority of deaths,<ref name="Sarkar-2009" /> recent evidence suggests that P. vivax malaria is associated with potentially life-threatening conditions about as often as with a diagnosis of P. falciparum infection.<ref name="Baird-2013" /> P. vivax proportionally is more common outside Africa.<ref name="Arnott-2012" /> Some cases have been documented of human infections with several species of Plasmodium from higher apes, but except for P. knowlesi—a zoonotic species that causes malaria in macaques<ref name="Collins-2012" />—these are mostly of limited public health importance.<ref name="Collins-2009" />
The Anopheles mosquitos initially get infected by Plasmodium by taking a blood meal from a previously Plasmodium infected person or animal.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Parasites are then typically introduced by the bite of an infected Anopheles mosquito. Some of these inoculated parasites, called "sporozoites", probably remain in the skin,<ref>Template:Cite journal</ref> but others travel in the bloodstream to the liver, where they invade hepatocytes.<ref name="Cowman-2016">Template:Cite journal</ref> They grow and divide in the liver for 2–10 days, with each infected hepatocyte eventually harboring up to 40,000 parasites.<ref name="Cowman-2016" /> The infected hepatocytes break down, releasing these invasive Plasmodium cells, called "merozoites", into the bloodstream. In the blood, the merozoites rapidly invade individual red blood cells, replicating over 24–72 hours to form 16–32 new merozoites.<ref name="Cowman-2016" /> The infected red blood cell lyses, and the new merozoites infect new red blood cells, resulting in a cycle that continuously amplifies the number of parasites in an infected person.<ref name="Cowman-2016" /> Over rounds of this infection cycle, a small portion of parasites do not replicate, but instead develop into early sexual stage parasites called male and female "gametocytes". These gametocytes develop in the bone marrow for 11 days, then return to the blood circulation to await uptake by the bite of another mosquito.<ref name="Cowman-2016" /> Once inside a mosquito, the gametocytes undergo sexual reproduction, and eventually form daughter sporozoites that migrate to the mosquito's salivary glands to be injected into a new host when the mosquito bites.<ref name="Cowman-2016" />
The liver infection causes no symptoms; all symptoms of malaria result from the infection of red blood cells.<ref name="Ashley-2018" /> Symptoms develop once there are more than around 100,000 parasites per milliliter of blood.<ref name="Ashley-2018" /> Many of the symptoms associated with severe malaria are caused by the tendency of P. falciparum to bind to blood vessel walls, resulting in damage to the affected vessels and surrounding tissue. Parasites sequestered in the blood vessels of the lung contribute to respiratory failure. In the brain, they contribute to coma. In the placenta they contribute to low birthweight and preterm labor, and increase the risk of abortion and stillbirth.<ref name="Ashley-2018" /> The destruction of red blood cells during infection often results in anemia, exacerbated by reduced production of new red blood cells during infection.<ref name="Ashley-2018" />
Only female mosquitoes feed on blood; male mosquitoes feed on plant nectar and do not transmit the disease. Females of the mosquito genus Anopheles prefer to feed at night. They usually start searching for a meal at dusk, and continue through the night until they succeed.<ref name="Arrow-2004" /> However, in Africa, due to the extensive use of bed nets, they began to bite earlier, before bed-net time.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Malaria parasites can also be transmitted by blood transfusions, although this is rare.<ref name="Owusu-Ofori-2010" />
Recurrent malariaEdit
Symptoms of malaria can recur after varying symptom-free periods. Depending upon the cause, recurrence can be classified as either recrudescence, relapse, or reinfection. Recrudescence is when symptoms return after a symptom-free period due to failure to remove blood-stage parasites by adequate treatment.Template:Sfn Relapse is when symptoms reappear after the parasites have been eliminated from the blood but have persisted as dormant hypnozoites<ref>Template:Cite journal</ref> in liver cells. Relapse commonly occurs between 8 and 24 weeks after the initial symptoms and is often seen in P. vivax and P. ovale infections.<ref name="Nadjm-2012" /> P. vivax malaria cases in temperate areas often involve overwintering by hypnozoites, with relapses beginning the year after the mosquito bite.<ref name="White-2011" /> Reinfection means that parasites were eliminated from the entire body but new parasites were then introduced. Reinfection cannot readily be distinguished from relapse and recrudescence, although recurrence of infection within two weeks of treatment ending is typically attributed to treatment failure.Template:Sfn People may develop some immunity when exposed to frequent infections.<ref name="Tran-2012" />
PathophysiologyEdit
Malaria infection develops via two phases: one that involves the liver (exoerythrocytic phase), and one that involves red blood cells, or erythrocytes (erythrocytic phase). When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver where they infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days.<ref name="Bledsoe-2005" />
After a potential dormant period in the liver, these organisms differentiate to yield thousands of merozoites, which, following rupture of their host cells, escape into the blood and infect red blood cells to begin the erythrocytic stage of the life cycle.<ref name="Bledsoe-2005" /> The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.<ref name="Vaughan-2008" />
The parasites multiply asexually within red blood cells, periodically breaking out to infect new ones. This repeated cycle results in synchronized waves of merozoites escaping and invading red blood cells, which cause the characteristic fever patterns.<ref name="Bledsoe-2005" />
Some P. vivax sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead, produce hypnozoites that remain dormant for periods ranging from several months (7–10 months is typical) to several years.<ref name="White-2011" /> After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in P. vivax infections,<ref name="White-2011" /> although their existence in P. ovale is uncertain.<ref name="Richter-2010" />
The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen.<ref name="Tilley-2011" /> The blockage of the microvasculature causes symptoms such as those in placental malaria.<ref name="Mens-2010" /> Sequestered red blood cells can breach the blood–brain barrier and cause cerebral malaria.<ref name="Rénia-2012" />
Genetic resistanceEdit
{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Due to the high levels of mortality and morbidity caused by malaria—especially the P. falciparum species—it has placed the greatest selective pressure on the human genome in recent history. Several genetic factors provide some resistance to it including sickle cell trait, thalassaemia traits, glucose-6-phosphate dehydrogenase deficiency, and the absence of Duffy antigens on red blood cells.<ref>Template:Cite journal</ref><ref name="Kwiatkowski-2005" /><ref name="Hedrick-2011" />
The effect of sickle cell trait on malaria immunity illustrates some evolutionary trade-offs that have occurred because of endemic malaria. Sickle cell trait causes a change in the haemoglobin molecule in the blood. Normally, red blood cells have a very flexible, biconcave shape that allows them to move through narrow capillaries; however, when the modified haemoglobin S molecules are exposed to low amounts of oxygen, or crowd together due to dehydration, they can stick together forming strands that cause the cell to distort into a curved sickle shape. In these strands, the molecule is not as effective in taking or releasing oxygen, and the cell is not flexible enough to circulate freely. In the early stages of malaria, the parasite can cause infected red cells to sickle, and so they are removed from circulation sooner. This reduces the frequency with which malaria parasites complete their life cycle in the cell. Individuals who are homozygous (with two copies of the abnormal haemoglobin beta allele) have sickle-cell anaemia, while those who are heterozygous (with one abnormal allele and one normal allele) experience resistance to malaria without severe anaemia. Although the shorter life expectancy for those with the homozygous condition would tend to disfavour the trait's survival, the trait is preserved in malaria-prone regions because of the benefits provided by the heterozygous form.<ref name="Hedrick-2011" /><ref name="Weatherall-2008" />
Liver dysfunctionEdit
Liver dysfunction as a result of malaria is uncommon and usually only occurs in those with another liver condition such as viral hepatitis or chronic liver disease. The syndrome is sometimes called malarial hepatitis.<ref name="Bhalla-2006" /> While it has been considered a rare occurrence, malarial hepatopathy has seen an increase, particularly in Southeast Asia and India. Liver compromise in people with malaria correlates with a greater likelihood of complications and death.<ref name="Bhalla-2006" />
Effects on vaccine responseEdit
Malaria infection affects the immune responses following vaccination for various diseases. For example, malaria suppresses immune responses to polysaccharide vaccines. A potential solution is to give curative treatment before vaccination in areas where malaria is present.<ref name="Cunnington-2010">Template:Cite journal</ref>
DiagnosisEdit
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Due to the non-specific nature of malaria symptoms, diagnosis is typically suspected based on symptoms and travel history, then confirmed with a laboratory test to detect the presence of the parasite in the blood (parasitological test). In areas where malaria is common, the World Health Organization (WHO) recommends clinicians suspect malaria in any person who reports having fevers, or who has a current temperature above 37.5 °C without any other obvious cause.<ref name="WHO-2021a">Template:Cite book</ref> Malaria should be suspected in children with signs of anemia: pale palms or a laboratory test showing hemoglobin levels below 8 grams per deciliter of blood.<ref name="WHO-2021a" /> In areas of the world with little to no malaria, the WHO recommends only testing people with possible exposure to malaria (typically travel to a malaria-endemic area) and unexplained fever.<ref name="WHO-2021a" />
In sub-Saharan Africa, testing is low, with only about one in four (28%) of children with a fever receiving medical advice or a rapid diagnostic test in 2021. There was a 10-percentage point gap in testing between the richest and the poorest children (33% vs 23%). Additionally, a greater proportion of children in Eastern and Southern Africa (36%) were tested than in West and Central Africa (21%).<ref name="UNICEF DATA-2" /> According to UNICEF, 61% of children with a fever were taken for advice or treatment from a health facility or provider in 2021. Disparities are also observed by wealth, with an 18 percentage point difference in care-seeking behaviour between children in the richest (71%) and the poorest (53%) households.<ref name="UNICEF DATA-2" />
Malaria is usually confirmed by the microscopic examination of blood films or by antigen-based rapid diagnostic tests (RDT). Microscopy—i.e. examining Giemsa-stained blood with a light microscope—is the gold standard for malaria diagnosis.<ref name="Ashley-2018" /> Microscopists typically examine both a "thick film" of blood, allowing them to scan many blood cells in a short time, and a "thin film" of blood, allowing them to clearly see individual parasites and identify the infecting Plasmodium species.<ref name="Ashley-2018" /> Under typical field laboratory conditions, a microscopist can detect parasites when there are at least 100 parasites per microliter of blood, which is around the lower range of symptomatic infection.<ref name="WHO-2021a" /> Microscopic diagnosis is relatively resource intensive, requiring trained personnel, specific equipment and a consistent supply of microscopy slides and stains.<ref name="WHO-2021a" />
In places where microscopy is unavailable, malaria is diagnosed with RDTs, rapid antigen tests that detect parasite proteins in a fingerstick blood sample.<ref name="WHO-2021a" /> A variety of RDTs are commercially available, targeting the parasite proteins histidine rich protein 2 (HRP2, detects P. falciparum only), lactate dehydrogenase, or aldolase.<ref name="WHO-2021a" /> The HRP2 test is widely used in Africa, where P. falciparum predominates.<ref name="Ashley-2018" /> However, since HRP2 persists in the blood for up to five weeks after an infection is treated, an HRP2 test sometimes cannot distinguish whether someone currently has malaria or previously had it.<ref name="WHO-2021a" /> Additionally, some P. falciparum parasites in the Amazon region lack the HRP2 gene, complicating detection.<ref name="WHO-2021a" /> Some P. falciparum species also have genetic deletions of the genes coding for the HRP2 antigen; leading to possible false negative results.<ref name="Daily 2025">Template:Cite journal</ref> Rapid tests also cannot quantify the parasite burden in a person.<ref name="Daily 2025" /> RDTs are fast and easily deployed to places without full diagnostic laboratories.<ref name="WHO-2021a" /" /> However they give considerably less information than microscopy, and sometimes vary in quality from producer to producer and lot to lot.<ref name="WHO-2021a" />
Serological tests to detect antibodies against Plasmodium from the blood have been developed, but are not used for malaria diagnosis due to their relatively poor sensitivity and specificity. Highly sensitive nucleic acid amplification tests have been developed, but are not used clinically due to their relatively high cost, and poor specificity for active infections.<ref name="WHO-2021a"/>
ClassificationEdit
Malaria is classified into either "severe" or "uncomplicated" by the World Health Organization (WHO).<ref name="Nadjm-2012" /> It is deemed severe when any of the following criteria are present, otherwise it is considered uncomplicated.Template:Sfn
- Decreased consciousness
- Significant weakness such that the person is unable to walk
- Inability to feed
- Two or more convulsions
- Low blood pressure (less than 70 mmHg in adults and 50 mmHg in children)
- Breathing problems
- Circulatory shock
- Kidney failure or hemoglobin in the urine
- Bleeding problems, or hemoglobin less than 50 g/L (5 g/dL)
- Pulmonary oedema
- Blood glucose less than 2.2 mmol/L (40 mg/dL)
- Acidosis or lactate levels of greater than 5 mmol/L
- A parasite level in the blood of greater than 100,000 per microlitre (μL) in low-intensity transmission areas, or 250,000 per μL in high-intensity transmission areas
Cerebral malaria is defined as a severe P. falciparum-malaria presenting with neurological symptoms, including coma (with a Glasgow coma scale less than 11, or a Blantyre coma scale less than 3), or with a coma that lasts longer than 30 minutes after a seizure.Template:Sfn
PreventionEdit
Methods used to prevent malaria include medications, mosquito elimination and the prevention of bites. As of 2023, there are two malaria vaccines, approved for use in children by the WHO: RTS,S and R21.<ref name="WHO recommends R21-2023"/><ref name="www.who.int-3">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The presence of malaria in an area requires a combination of high human population density, high Anopheles mosquito population density and high rates of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these is lowered sufficiently, the parasite eventually disappears from that area, as happened in North America, Europe, and parts of the Middle East. However, unless the parasite is eliminated from the whole world, it could re-establish if conditions revert to a combination that favors the parasite's reproduction. Furthermore, the cost per person of eliminating anopheles mosquitoes rises with decreasing population density, making it economically unfeasible in some areas.<ref name="World Health Organization-1958" />
Prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the initial costs required are out of reach of many of the world's poorest people. There is a wide difference in the costs of control (i.e. maintenance of low endemicity) and elimination programs between countries. For example, in China—whose government in 2010 announced a strategy to pursue malaria elimination in the Chinese provinces—the required investment is a small proportion of public expenditure on health. In contrast, a similar programme in Tanzania would cost an estimated one-fifth of the public health budget.<ref name="Sabot-2010" /> In 2021, the World Health Organization confirmed that China has eliminated malaria.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2023, the World Health Organization confirmed that Azerbaijan, Tajikistan, and Belize have eliminated malaria.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
In areas where malaria is common, children under five years old often have anaemia, which is sometimes due to malaria. Giving children with anaemia in these areas preventive antimalarial medication improves red blood cell levels slightly but does not affect the risk of death or need for hospitalisation.<ref>Template:Cite journal</ref>
Mosquito controlEdit
Vector control refers to methods used to decrease malaria by reducing the levels of transmission by mosquitoes. For individual protection, the most effective insect repellents are based on DEET or picaridin.<ref name="Kajfasz-2009" /> However, there is insufficient evidence that mosquito repellents can prevent malaria infection.<ref>Template:Cite journal</ref> Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are effective, have been commonly used to prevent malaria, and their use has contributed significantly to the decrease in malaria in the 21st century.<ref name="Fox-2022">Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="Pluess-2010" /> ITNs and IRS may not be sufficient to eliminate the disease, as these interventions depend on how many people use nets, how many gaps in insecticide there are (low coverage areas), if people are not protected when outside of the home, and an increase in mosquitoes that are resistant to insecticides.<ref name="Fox-2022" /> Modifications to people's houses to prevent mosquito exposure may be an important long term prevention measure.<ref name="Fox-2022" />
Insecticide-treated netsEdit
Mosquito nets help keep mosquitoes away from people and reduce infection rates and transmission of malaria. Nets are not a perfect barrier and are often treated with an insecticide designed to kill the mosquito before it has time to find a way past the net. Insecticide-treated nets (ITNs) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net.<ref name="Raghavendra-2011" /> Between 2000 and 2008, the use of ITNs saved the lives of an estimated 250,000 infants in Sub-Saharan Africa.<ref name="Howitt-2012" /> According to UNICEF, only 36% of households had sufficient ITNs for all household members in 2019.<ref name="UNICEF DATA">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2000, 1.7 million (1.8%) African children living in areas of the world where malaria is common were protected by an ITN. That number increased to 20.3 million (18.5%) African children using ITNs in 2007, leaving 89.6 million children unprotected<ref name="Noor-2009" /> and to 68% African children using mosquito nets in 2015.<ref name="UNICEF-2015" /> The percentage of children sleeping under ITNs in sub-Saharan Africa increased from less than 40% in 2011 to over 50% in 2021.<ref name="UNICEF DATA-2" /> Most nets are impregnated with pyrethroids, a class of insecticides with low toxicity. They are most effective when used from dusk to dawn.<ref>Template:Harvnb</ref> It is recommended to hang a large "bed net" above the center of a bed and either tuck the edges under the mattress or make sure it is large enough such that it touches the ground.<ref>Template:Cite book</ref> ITNs are beneficial towards pregnancy outcomes in malaria-endemic regions in Africa but more data is needed in Asia and Latin America.<ref>Template:Cite journal</ref>
In areas of high malaria resistance, piperonyl butoxide (PBO) combined with pyrethroids in mosquito netting is effective in reducing malaria infection rates.<ref name="Gleave-2021">Template:Cite journal</ref> Questions remain concerning the durability of PBO on nets as the effect on mosquito mortality was not sustained after twenty washes in experimental trials.<ref name="Gleave-2021" />
UNICEF notes that the use of insecticide-treated nets has been increased since 2000 through accelerated production, procurement and delivery, stating that "over 2.5 billion ITNs have been distributed globally since 2004, with 87% (2.2 billion) distributed in sub-Saharan Africa. In 2021, manufacturers delivered about 220 million ITNs to malaria endemic countries, a decrease of 9 million ITNs compared with 2020 and 33 million less than were delivered in 2019".<ref name="UNICEF-2023"/> As of 2021, 66% of households in sub-Saharan Africa had ITNs, with figures "ranging from 31 per cent in Angola in 2016 to approximately 97 per cent in Guinea-Bissau in 2019".<ref name="UNICEF-2023"/> Slightly more than half of the households with an ITN had enough of them to protect all members of the household, however.<ref name="UNICEF-2023"/>
Indoor residual sprayingEdit
Indoor residual spraying is the spraying of insecticides on the walls inside a home. After feeding, many mosquitoes rest on a nearby surface while digesting the bloodmeal, so if the walls of houses have been coated with insecticides, the resting mosquitoes can be killed before they can bite another person and transfer the malaria parasite.<ref name="Enayati-2010" /> As of 2006, the World Health Organization recommends 12 insecticides in IRS operations, including DDT and the pyrethroids cyfluthrin and deltamethrin.<ref name="WHO-2006" /> This public health use of small amounts of DDT is permitted under the Stockholm Convention, which prohibits its agricultural use.<ref name="van den Berg-2009" /> One problem with all forms of IRS is insecticide resistance. Mosquitoes affected by IRS tend to rest and live indoors, and due to the irritation caused by spraying, their descendants tend to rest and live outdoors, meaning that they are less affected by the IRS.<ref name="Pates-2005" /> Communities using insecticide treated nets, in addition to indoor residual spraying with 'non-pyrethroid-like' insecticides found associated reductions in malaria.<ref name="Pryce-2022">Template:Cite journal</ref> Additionally, the use of 'pyrethroid-like' insecticides in addition to indoor residual spraying did not result in a detectable additional benefit in communities using insecticide treated nets.<ref name="Pryce-2022" />
Housing modificationsEdit
Housing is a risk factor for malaria and modifying the house as a prevention measure may be a sustainable strategy that does not rely on the effectiveness of insecticides such as pyrethroids.<ref name="Fox-2022" /><ref>Template:Cite journal</ref> The physical environment inside and outside the home that may improve the density of mosquitoes are considerations. Examples of potential modifications include how close the home is to mosquito breeding sites, drainage and water supply near the home, availability of mosquito resting sites (vegetation around the home), the proximity to live stock and domestic animals, and physical improvements or modifications to the design of the home to prevent mosquitoes from entering,<ref name="Fox-2022" /> such as window screens.
In addition to installing window screens, house screening measures include screening ceilings, doors, and eaves. In 2021, the World Health Organization's (WHO) Guideline Development Group conditionally recommended screening houses in this manner to reduce malaria transmission.<ref name="WHO Guidelines for Malaria-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> However, the WHO does point out that there are local considerations that need to be addressed when incorporating these techniques. These considerations include the delivery method, maintenance, house design, feasibility, resource needs, and scalability.<ref name="WHO Guidelines for Malaria-2023" />
Several studies have suggested that screening houses can have a significant effect on malaria transmission. Beyond the protective barrier screening provides, it also does not call for daily behavioral changes in the household.<ref name="Nalinya-2022">Template:Cite journal</ref> Screening eaves can also have a community-level protective effect, ultimately reducing mosquito-biting densities in neighboring houses that do not have this intervention in place.<ref name="Nalinya-2022" />
In some cases, studies have used insecticide-treated (e.g., transfluthrin) or untreated netting to deter mosquito entry.<ref name="Nalinya-2022" /> One widely used intervention is the In2Care BV EaveTube. In 2021, In2Care BV received funding from the United States Agency for International Development to develop a ventilation tube that would be installed in housing walls.<ref name="USAID DIV Impacts-2024">{{#invoke:citation/CS1|citation |CitationClass=web }}Template:Dead linkTemplate:Cbignore</ref> When mosquitoes approach households, the goal is for them to encounter these EaveTubes instead. Inside these EaveTubes is insecticide-treated netting that is lethal to insecticide-resistant mosquitoes.<ref name="USAID DIV Impacts-2024" /> This approach to mosquito control is called the Lethal House Lure method. The WHO is currently evaluating the efficacy of this product for widespread use.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Mass drug administrationEdit
Mass drug administration (MDA) involves the administration of drugs to the entire population of an area regardless of disease status.<ref>Template:Cite journal</ref> A subtype, known as seasonal malaria chemoproprophylaxis (or chemoprevention) involves giving those vulnerable to complications from malaria (such as young children under 5, or pregnant women) medications to prevent malaria.<ref name="Daily 2025" /> This may be done during certain seasons, where mosquitos are more likely to spread the disease. Malaria vaccination, when combined with seasonal chemoprevention has been shown to prevent more cases of malaria compared to vaccination alone.<ref name="Dicko 2024">Template:Cite journal</ref>
A 2021 Cochrane review on the use of community administration of ivermectin found that, to date, low quality evidence shows no significant effect on reducing incidence of malaria transmission from the community administration of ivermectin.<ref>Template:Cite journal</ref>
Mosquito-targeted drug deliveryEdit
One potential way to reduce the burden of malaria is to target the infection in mosquitoes, before it enters the mammalian host (during sporogeny).<ref>Template:Cite journal</ref> Drugs may be used for this purpose which have unacceptable toxicity profiles in humans. For example, aminoquinoline derivates show toxicity in humans,<ref name="WHO" /> but this has not been shown in mosquitoes. Primaquine is particularly effective against Plasmodium gametocytes. Likewise, pyrroloquinazolinediamines show unacceptable toxicity in mammals,<ref>Template:Cite journal</ref> but it is unknown whether this is the case in mosquitoes. Pyronaridine, thiostrepton, and pyrimethamine have been shown to dramatically reduce ookinete formation in P. berghei, while artefenomel, NPC-1161B, and tert-butyl isoquine reduce exflagellation in P. Falciparum.<ref>Template:Cite journal</ref>
Other mosquito control methodsEdit
People have tried a number of other methods to reduce mosquito bites and slow the spread of malaria. Efforts to decrease mosquito larvae by decreasing the availability of open water where they develop, or by adding substances to decrease their development, are effective in some locations.<ref>Template:Cite journal</ref> Electronic mosquito repellent devices, which make very high-frequency sounds that are supposed to keep female mosquitoes away, have no supporting evidence of effectiveness.<ref name="Enayati-2007" /> There is a low certainty evidence that fogging may have an effect on malaria transmission.<ref>Template:Cite journal</ref> Larviciding by hand delivery of chemical or microbial insecticides into water bodies containing low larval distribution may reduce malarial transmission.<ref>Template:Cite journal</ref> There is insufficient evidence to determine whether larvivorous fish can decrease mosquito density and transmission in the area.<ref>Template:Cite journal</ref>
MedicationsEdit
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There are a number of medications that can help prevent or interrupt malaria in travellers to places where infection is common. Many of these medications are also used in treatment. In places where Plasmodium is resistant to one or more medications, three medications—mefloquine, doxycycline, or the combination of atovaquone/proguanil (Malarone)—are frequently used for prevention.<ref name="Tickell-Painter-2017" /> Doxycycline and the atovaquone/proguanil are better tolerated while mefloquine is taken once a week.<ref name="Tickell-Painter-2017">Template:Cite journal</ref> Areas of the world with chloroquine-sensitive malaria are uncommon.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Antimalarial mass drug administration to an entire population at the same time may reduce the risk of contracting malaria in the population, however the effectiveness of mass drug administration may vary depending on the prevalence of malaria in the area.<ref name="Shah-2021">Template:Cite journal</ref> Other factors such as drug administration plus other protective measures such as mosquito control, the proportion of people treated in the area, and the risk of reinfection with malaria may play a role in the effectiveness of mass drug treatment approaches.<ref name="Shah-2021" />
The protective effect does not begin immediately, and people visiting areas where malaria exists usually start taking the drugs one to two weeks before they arrive, and continue taking them for four weeks after leaving (except for atovaquone/proguanil, which only needs to be started two days before and continued for seven days afterward).<ref name="Freedman-2008" /> The use of preventive drugs is often not practical for those who live in areas where malaria exists, and their use is usually given only to pregnant women and short-term visitors. This is due to the cost of the drugs, side effects from long-term use, and the difficulty in obtaining antimalarial drugs outside of wealthy nations.<ref name="Fernando-2011" /> During pregnancy, medication to prevent malaria has been found to improve the weight of the baby at birth and decrease the risk of anaemia in the mother.<ref>Template:Cite journal</ref> The use of preventive drugs where malaria-bearing mosquitoes are present may encourage the development of partial resistance.<ref name="Turschner-2009" />
Giving antimalarial drugs to infants through intermittent preventive therapy can reduce the risk of having malaria infection, hospital admission, and anaemia.<ref>Template:Cite journal</ref>
Mefloquine is more effective than sulfadoxine-pyrimethamine in preventing malaria for HIV-negative pregnant women. Cotrimoxazole is effective in preventing malaria infection and reduce the risk of getting anaemia in HIV-positive women.<ref>Template:Cite journal</ref> Giving Dihydroartemisinin/piperaquine and mefloquine in addition to the daily cotrimoxazole to HIV-positive pregnant women seem to be more efficient in preventing malaria infection than cotrimoxazole alone.<ref>Template:Cite journal</ref>
Prompt treatment of confirmed cases with artemisinin-based combination therapies (ACTs) may also reduce transmission.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Research on malaria vaccinesEdit
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Malaria vaccines have been another goal of research. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunising mice with live, radiation-attenuated sporozoites, which provided significant protection to the mice upon subsequent injection with normal, viable sporozoites. Since the 1970s, there has been considerable progress in developing similar vaccination strategies for humans.<ref name="Vanderberg-2009" />
In 2013, WHO and the malaria vaccine funders group set a goal to develop vaccines designed to interrupt malaria transmission with malaria eradication's long-term goal.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The first vaccine, called RTS,S, was approved by European regulators in 2015.<ref name="Walsh-2015" /> As of 2023, two malaria vaccines have been licensed for use.<ref name="WHO recommends R21-2023"/> Other approaches to combat malaria may require investing more in research and greater primary health care.Template:Sfn Continuing surveillance will also be important to prevent the return of malaria in countries where the disease has been eliminated.<ref>Template:Cite journal</ref>
As of 2019 it is undergoing pilot trials in 3 sub-Saharan African countries—Ghana, Kenya and Malawi—as part of the WHO's Malaria Vaccine Implementation Programme (MVIP).<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Immunity (or, more accurately, tolerance) to P. falciparum malaria does occur naturally, but only in response to years of repeated infection.<ref name="Tran-2012" /><ref>Template:Cite journal</ref> An individual can be protected from a P. falciparum infection if they receive about a thousand bites from mosquitoes that carry a version of the parasite rendered non-infective by a dose of X-ray irradiation.<ref name="Hill-2011" /> The highly polymorphic nature of many P. falciparum proteins results in significant challenges to vaccine design. Vaccine candidates that target antigens on gametes, zygotes, or ookinetes in the mosquito midgut aim to block the transmission of malaria. These transmission-blocking vaccines induce antibodies in the human blood; when a mosquito takes a blood meal from a protected individual, these antibodies prevent the parasite from completing its development in the mosquito.<ref name="Crompton-2010" /> Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have been inadequate on their own.<ref name="Graves-2006b" /> For example, SPf66 was tested extensively in areas where the disease was common in the 1990s, but trials showed it to be insufficiently effective.<ref name="Graves-2006a" />
As of 2020, the RTS,S vaccine has been shown to reduce the risk of malaria by about 40% in children in Africa.<ref name="www.who.int-3" /><ref name="WHO PP-2016">Template:Cite journal</ref> A preprint study of the R21 vaccine has shown 77% vaccine efficacy.Template:Update inline<ref>Template:Cite journal</ref>
In 2021, researchers from the University of Oxford reported findings from a Phase IIb trial of a candidate malaria vaccine, R21/Matrix-M, which demonstrated efficacy of 77% over 12-months of follow-up. This vaccine is the first to meet the World Health Organization's Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy.<ref>Malaria vaccine becomes first to achieve WHO-specified 75% efficacy goal Template:Webarchive, News Release 23 April 2021, University of Oxford</ref>
Germany-based BioNTECH SE is developing an mRNA-based malaria vaccine BNT165<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> which has recently initiated a Phase 1 study [clinicaltrials.gov identifier: NCT05581641] in December 2022. The vaccine, based on the circumsporozoite protein (CSP) is being tested in adults aged 18–55 yrs at 3 dose levels to select a safe and tolerable dose of a three-dose schedule. Unlike GSK's RTS,S (AS01) and Serum Institute of India's R21/MatrixM, BNT-165 is being studied in adult age groups meaning it could be developed for Western travelers as well as those living in endemic countries. For the travelers profile, a recent commercial assessment forecast potential gross revenues of BNT-165 at $479m (2030) 5-yrs post launch, POS-adjusted revenues.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
OthersEdit
Community participation and health education strategies promoting awareness of malaria and the importance of control measures have been successfully used to reduce the incidence of malaria in some areas of the developing world.<ref name="Lalloo-2006" /> Recognising the disease in the early stages can prevent it from becoming fatal. Education can also inform people to cover over areas of stagnant, still water, such as water tanks that are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people. This is generally used in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas.<ref name="Mehlhorn-2016" /> Intermittent preventive therapy is another intervention that has been used successfully to control malaria in pregnant women and infants,<ref name="Bardají-2012" /> and in preschool children where transmission is seasonal.<ref name="Meremikwu-2012a" />
TreatmentEdit
Malaria is treated with antimalarial medications; the ones used depend on the type and severity of the disease.<ref>Template:Cite journal</ref> While medications against fever are commonly used, their effects on outcomes are not clear.<ref>Template:Cite journal</ref><ref name="Meremikwu-2012b" /> Providing free antimalarial drugs to households may reduce childhood deaths when used appropriately. Programmes which presumptively treat all causes of fever with antimalarial drugs may lead to overuse of antimalarials and undertreat other causes of fever. Nevertheless, the use of malaria rapid-diagnostic kits can help to reduce over-usage of antimalarials.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Uncomplicated malariaEdit
Simple or uncomplicated malaria may be treated with oral medications. Artemisinin drugs are effective and safe in treating uncomplicated malaria.<ref>Template:Cite journal</ref> Artemisinin in combination with other antimalarials (known as artemisinin-combination therapy, or ACT) is about 90% effective when used to treat uncomplicated malaria.<ref name="Howitt-2012" /> The most effective treatment for P. falciparum infection is the use of ACT, which decreases resistance to any single drug component.<ref>Template:Cite journal</ref><ref name="Kokwaro-2009" /> Artemether-lumefantrine (six-dose regimen) is more effective than the artemether-lumefantrine (four-dose regimen) or other regimens not containing artemisinin derivatives in treating falciparum malaria.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Another recommended combination is dihydroartemisinin and piperaquine.Template:Sfn<ref name="Keating-2012" /><ref>Template:Cite journal</ref> Artemisinin-naphthoquine combination therapy showed promising results in treating falciparum malaria but more research is needed to establish its efficacy as a reliable treatment.<ref>Template:Cite journal</ref> Artesunate plus mefloquine performs better than mefloquine alone in treating uncomplicated falciparum malaria in low transmission settings.<ref>Template:Cite journal</ref> Atovaquone-proguanil is effective against uncomplicated falciparum with a possible failure rate of 5% to 10%; the addition of artesunate may reduce failure rate.<ref>Template:Cite journal</ref> Azithromycin monotherapy or combination therapy has not shown effectiveness in treating Plasmodium falciparum or Plasmodium vivax malaria.<ref>Template:Cite journal</ref> Amodiaquine plus sulfadoxine-pyrimethamine may achieve less treatment failures when compared to sulfadoxine-pyrimethamine alone in uncomplicated falciparum malaria.<ref>Template:Cite journal</ref> There is insufficient data on chlorproguanil-dapsone in treating uncomplicated falciparum malaria.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> The addition of primaquine with artemisinin-based combination therapy for falciparum malaria reduces its transmission at day 3–4 and day 8 of infection.<ref>Template:Cite journal</ref> Sulfadoxine-pyrimethamine plus artesunate is better than sulfadoxine-pyrimethamine plus amodiaquine in controlling treatment failure at day 28. However, the latter is better than the former in reducing gametocytes in blood at day 7.<ref>Template:Cite journal</ref>
Infection with P. vivax, P. ovale or P. malariae usually does not require hospitalisation. Treatment of P. vivax malaria requires both elimination of the parasite in the blood with chloroquine or with artemisinin-based combination therapy and clearance of parasites from the liver with an 8-aminoquinoline agent such as primaquine or tafenoquine.<ref name="Waters-2011" /><ref>Template:Cite journal</ref> These two drugs act against blood stages as well, the extent to which they do so still being under investigation.<ref>Template:Cite journal</ref>
To treat malaria during pregnancy, the WHO recommends the use of quinine plus clindamycin early in the pregnancy (1st trimester), and ACT in later stages (2nd and 3rd trimesters).<ref>Template:Cite journal</ref><ref name="Manyando-2012" /> There is limited safety data on the antimalarial drugs in pregnancy.<ref>Template:Cite journal</ref>
Severe and complicated malariaEdit
Cases of severe and complicated malaria are almost always caused by infection with P. falciparum. The other species usually cause only febrile disease.<ref>Template:Cite journal</ref> Severe and complicated malaria cases are medical emergencies since mortality rates are high (10% to 50%).<ref>Template:Cite journal</ref>
Recommended treatment for severe malaria is the intravenous use of antimalarial drugs. For severe malaria, parenteral artesunate was superior to quinine in both children and adults.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Sinclair-2012" /> In another systematic review, artemisinin derivatives (artemether and arteether) were as efficacious as quinine in the treatment of cerebral malaria in children.<ref>Template:Cite journal</ref> Treatment of severe malaria involves supportive measures that are best done in a critical care unit. This includes the management of high fevers and the seizures that may result from it. It also includes monitoring for poor breathing effort, low blood sugar, and low blood potassium.<ref name="Sarkar-2009" /> Artemisinin derivatives have the same or better efficacy than quinolones in preventing deaths in severe or complicated malaria.<ref>Template:Cite journal</ref> Quinine loading dose helps to shorten the duration of fever and increases parasite clearance from the body.<ref>Template:Cite journal</ref> There is no difference in effectiveness when using intrarectal quinine compared to intravenous or intramuscular quinine in treating uncomplicated/complicated falciparum malaria.<ref>Template:Cite journal</ref> There is insufficient evidence for intramuscular arteether to treat severe malaria.<ref>Template:Cite journal</ref> The provision of rectal artesunate before transfer to hospital may reduce the rate of death for children with severe malaria.<ref>Template:Cite journal</ref> In children with malaria and concomitant hypoglycaemia, sublingual administration of glucose appears to result in better increases in blood sugar after 20 minutes when compared to oral administration, based on very limited data.<ref>Template:Cite journal</ref>
Cerebral malaria is the form of severe and complicated malaria with the worst neurological symptoms.<ref>Template:Cite journal</ref> There is insufficient data on whether osmotic agents such as mannitol or urea are effective in treating cerebral malaria.<ref>Template:Cite journal</ref> Routine phenobarbitone in cerebral malaria is associated with fewer convulsions but possibly more deaths.<ref>Template:Cite journal</ref> There is no evidence that steroids would bring treatment benefits for cerebral malaria.<ref>Template:Cite journal</ref>
Managing cerebral malariaEdit
Cerebral malaria usually makes a patient comatose. If the cause of the coma is in doubt, testing for other locally prevalent causes of encephalopathy (bacterial, viral or fungal infection) should be carried out. In areas where there is a high prevalence of malaria infection (e.g. tropical region) treatment can start without testing first.<ref name="US CDC-2022"/> To manage the cerebral malaria when confirmed the following can be done:
- People who are in coma should be given meticulous nursing care ( monitor vital signs, turn patient every 2 hours, avoid lying the patient in a wet bed etc.)
- A sterile urethral catheter should be inserted to help with urinating
- To aspirate stomach content, a sterile nasogastric tube should be inserted.
- In the occasion of convulsions, a slow intravenous injection of benzodiazepine is administered.<ref>Template:Cite book</ref>
There is insufficient evidence to show that blood transfusion is useful in either reducing deaths for children with severe anaemia or in improving their haematocrit in one month.<ref>Template:Cite journal</ref> There is insufficient evidence that iron chelating agents such as deferoxamine and deferiprone improve outcomes of those with malaria falciparum infection.<ref>Template:Cite journal</ref>
Monoclonal antibodiesEdit
A 2022 clinical trial shows that a monoclonal antibody mAb L9LS offers protection against malaria. It binds the Plasmodium falciparum circumsporozoite protein (CSP-1), essential to disease, and makes it ineffective.<ref name="Nature Biotech-2022">Template:Cite journal</ref>
ResistanceEdit
Drug resistance poses a growing problem in 21st-century malaria treatment.<ref name="Sinha-2014" /> In the 2000s (decade), malaria with partial resistance to artemisins emerged in Southeast Asia.<ref name="O'Brien-2011" /><ref name="Fairhurst-2012" /> Resistance is now common against all classes of antimalarial drugs apart from artemisinins. Treatment of resistant strains became increasingly dependent on this class of drugs. The cost of artemisinins limits their use in the developing world.<ref name="White-2008" /> Malaria strains found on the Cambodia–Thailand border are resistant to combination therapies that include artemisinins, and may, therefore, be untreatable.<ref name="Wongsrichanalai-2008" /> Exposure of the parasite population to artemisinin monotherapies in subtherapeutic doses for over 30 years and the availability of substandard artemisinins likely drove the selection of the resistant phenotype.<ref name="Dondorp-2010" /> Resistance to artemisinin has been detected in Cambodia, Myanmar, Thailand, and Vietnam,<ref>Template:Cite journal</ref> and there has been emerging resistance in Laos.<ref name="Briggs-2014">Template:Cite news</ref><ref name="Ashley-2014" /> Resistance to the combination of artemisinin and piperaquine was first detected in 2013 in Cambodia, and by 2019 had spread across Cambodia and into Laos, Thailand and Vietnam (with up to 80 percent of malaria parasites resistant in some regions).<ref>Template:Cite news</ref>
There is insufficient evidence in unit packaged antimalarial drugs in preventing treatment failures of malaria infection. However, if supported by training of healthcare providers and patient information, there is improvement in compliance of those receiving treatment.<ref>Template:Cite journal</ref>
PrognosisEdit
When properly treated, people with malaria can usually expect a complete recovery.<ref name="US CDC-2010b" /> However, severe malaria can progress extremely rapidly and cause death within hours or days.<ref name="Trampuz-2003" /> In the most severe cases of the disease, fatality rates can reach 20%, even with intensive care and treatment.<ref name="Nadjm-2012" /> Over the longer term, developmental impairments have been documented in children who have had episodes of severe malaria.<ref name="Fernando-2010" /> Chronic infection without severe disease can occur in an immune-deficiency syndrome associated with a decreased responsiveness to Salmonella bacteria and the Epstein–Barr virus.<ref name="Riley-2013" />
During childhood, malaria causes anaemia during a period of rapid brain development, and also direct brain damage resulting from cerebral malaria.<ref name="Fernando-2010" /> Some survivors of cerebral malaria have an increased risk of neurological and cognitive deficits, behavioural disorders, and epilepsy.<ref name="Idro-2010" /> Malaria prophylaxis was shown to improve cognitive function and school performance in clinical trials when compared to placebo groups.<ref name="Fernando-2010" />
EpidemiologyEdit
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The WHO estimates that in 2021 there were 247 million total cases of malaria resulting in 619,000 deaths.Template:Sfn Children under five years old are the most affected, accounting for 67% of malaria deaths worldwide in 2019.<ref name="WHO-2021">Template:Cite book</ref> About 125 million pregnant women are at risk of infection each year; in Sub-Saharan Africa, maternal malaria is associated with up to 200,000 estimated infant deaths yearly.<ref name="Hartman-2010" /> Since 2015, the WHO European Region has been free of malaria. The last country to report an indigenous malaria case was Tajikistan in 2014.Template:Sfn There are about 1300–1500 malaria cases per year in the United States.<ref name="Taylor-2012" /> The United States eradicated malaria as a major public health concern in 1951,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> though small outbreaks persist.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Locally acquired mosquito-borne malaria occurred in the United States in 2003, when eight cases of locally acquired P. vivax malaria were identified in Florida, and again in May 2023, in four cases, as well as one case in Texas,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and in August in one case in Maryland.<ref>Template:Cite news</ref> About 900 people died from the disease in Europe between 1993 and 2003.<ref name="Kajfasz-2009" /> Both the global incidence of disease and resulting mortality have declined in recent years. According to the WHO and UNICEF, deaths attributable to malaria in 2015 were reduced by 60%<ref name="UNICEF-2015">Template:Cite book</ref> from a 2000 estimate of 985,000, largely due to the widespread use of insecticide-treated nets and artemisinin-based combination therapies.<ref name="Howitt-2012" /> Between 2000 and 2019, malaria mortality rates among all ages halved from about 30 to 13 per 100,000 population at risk. During this period, malaria deaths among children under five also declined by nearly half (47%) from 781,000 in 2000 to 416,000 in 2019.<ref name="UNICEF DATA"/>
Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa. Eighty-five to ninty percent of malaria fatalities occur in Sub-Saharan Africa.<ref name="Layne-2006" /> An estimate for 2009 reported that countries with the highest death rate per 100,000 of population were Ivory Coast (86.15), Angola (56.93) and Burkina Faso (50.66).<ref name="Provost-2011" /> A 2010 estimate indicated the deadliest countries per population were Burkina Faso, Mozambique and Mali.<ref name="Murray-2012" /> The Malaria Atlas Project aims to map global levels of malaria, providing a way to determine the global spatial limits of the disease and to assess disease burden.<ref name="Guerra-2007" /><ref name="Hay-2010" /> This effort led to the publication of a map of P. falciparum endemicity in 2010 and an update in 2019.<ref name="Gething-2011" /><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> As of 2021, 84 countries have endemic malaria.Template:Sfn
The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other.<ref name="Greenwood-2002" /> Malaria is prevalent in tropical and subtropical regions because of rainfall, consistent high temperatures and high humidity, along with stagnant waters where mosquito larvae readily mature, providing them with the environment they need for continuous breeding.<ref name="Jamieson-2006" /> In drier areas, outbreaks of malaria have been predicted with reasonable accuracy by mapping rainfall.<ref name="Abeku-2007" /> Malaria is more common in rural areas than in cities. For example, several cities in the Greater Mekong Subregion of Southeast Asia are essentially malaria-free, but the disease is prevalent in many rural regions, including along international borders and forest fringes.<ref name="Cui-2012" /> In contrast, malaria in Africa is present in both rural and urban areas, though the risk is lower in the larger cities.<ref name="Machault-2011" />
According to the World Health Organization's 2023 World Malaria Report, there were an estimated 263 million malaria cases globally in 2023, up from 252 million in 2022. The number of malaria deaths stood at 597,000 in 2023, a slight decrease from 600,000 in 2022. The African region continues to bear a disproportionate share of the global malaria burden, accounting for approximately 94% of all cases and 95% of deaths.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Climate changeEdit
Climate change is likely to affect malaria transmission, but the degree of effect and the areas affected is uncertain.<ref name="Climate Change and Human Health—Risk and Responses">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Greater rainfall in certain areas of India, and following an El Niño event is associated with increased mosquito numbers.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Since 1900 there has been substantial change in temperature and rainfall over Africa.<ref>Template:Cite journal</ref> However, factors that contribute to how rainfall results in water for mosquito breeding are complex, incorporating the extent to which it is absorbed into soil and vegetation for example, or rates of runoff and evaporation.<ref name="Smith-2020">Template:Cite journal</ref> Recent research has provided a more in-depth picture of conditions across Africa, combining a malaria climatic suitability model with a continental-scale model representing real-world hydrological processes.<ref name="Smith-2020" />
Changes in geographic distributionEdit
Climate change has led to shifts in malaria-endemic regions, with the disease expanding into higher altitudes and previously malaria-free areas.<ref name=Caminade14>Template:Cite journal</ref> Rising temperatures allow mosquitoes to survive in regions that were once too cold for them, including highland areas in Africa, South America, and parts of Asia.<ref name=Caminade14/> A study analyzing malaria cases in Ethiopian and Colombian highlands found a strong correlation between increased temperatures and malaria incidence, demonstrating that climate change has made previously inhospitable areas suitable for transmission.<ref name=Siraj14>Template:Cite journal</ref>
Increased transmission seasonEdit
Malaria transmission is highly sensitive to temperature and rainfall patterns.<ref name=Siraj14/> Climate change has led to longer transmission seasons in tropical regions, where mosquitoes can breed year-round due to prolonged periods of high humidity and warm temperatures.<ref name=Sewe21>Template:Cite journal</ref> Research suggests that in parts of sub-Saharan Africa, the malaria transmission season has lengthened by several months, particularly in regions where warming has pushed temperatures into the optimal range for Plasmodium falciparum development.<ref name=Sewe21/> In regions such as West Africa and parts of India, increasing temperatures and prolonged rainy seasons have contributed to a rise in malaria cases.<ref name=Sewe21/> Some studies predict that by 2050, many malaria-endemic areas will experience a 20–30% increase in transmission duration due to warming trends.<ref name=Caminade14/>
Effects of extreme weather eventsEdit
Extreme weather events, such as heavy rainfall, flooding, and droughts, are increasing in frequency and intensity due to climate change, creating favorable conditions for malaria outbreaks.<ref name=Bouma96>Template:Cite journal</ref> Flooding provides ideal breeding grounds for mosquitoes by forming stagnant water pools, while droughts can also exacerbate malaria by forcing human populations to store water in open containers, which serve as mosquito habitats.<ref name=Bouma96/> This effect has been observed in parts of sub-Saharan Africa and South Asia, where prolonged drought periods were followed by spikes in malaria cases.<ref name=Bouma96/> A review of malaria outbreaks linked to climate variability found that El Niño events, which increase rainfall and temperatures in malaria-endemic regions, have been associated with significant surges in cases.<ref>Template:Cite journal</ref>
Resistance and adaptation of vectorsEdit
Higher temperatures accelerate the development of Plasmodium parasites within mosquitoes, potentially leading to increased transmission efficiency.<ref name=Shapiro17>Template:Cite journal</ref> Additionally, rising temperatures and changing environmental conditions have been linked to the spread of insecticide resistance in mosquito populations, complicating malaria control efforts.<ref name=Shapiro17/> A global survey found that Anopheles mosquitoes in Africa, Asia, and South America have developed increased resistance to commonly used insecticides such as pyrethroids.<ref>Template:Cite journal</ref>
Urbanization and malaria trendsEdit
Urbanization has a great effect on malaria. There are better healthcare and infrastructure in the cities which then reduce malaria. Whereas poorer areas with bad sanitation allow mosquitoes to thrive which then increase malaria.<ref>Template:Cite journal</ref> Some African cities have more malaria cases compared to suburban areas. In Bangkok, it has been shown that malaria has dropped due to better control.<ref>Template:Cite journal</ref>
HistoryEdit
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Although the parasite responsible for P. falciparum malaria has been in existence for 50,000–100,000 years, the population size of the parasite did not increase until about 10,000 years ago, concurrently with advances in agriculture<ref name="Harper-2010"/> and the development of human settlements. Close relatives of the human malaria parasites remain common in chimpanzees. Some evidence suggests that the P. falciparum malaria may have originated in gorillas.<ref name="Prugnolle-2011"/>
References to the unique periodic fevers of malaria are found throughout history.<ref name="Cox-2002"/> Ancient Indian physician Sushruta believed that the disease was caused due to biting insects,<ref>Template:Cite book</ref> long before the Roman Columella associated the disease with insects from swamps.<ref name="Strong-1944" /> Hippocrates described periodic fevers, labelling them tertian, quartan, subtertian and quotidian.<ref name="Strong-1944">Template:Cite book</ref> Malaria may have contributed to the decline of the Roman Empire,<ref name="BBC News-2001"/> and was so pervasive in Rome that it was known as the "Roman fever".<ref name="Sallares-2002"/> Several regions in ancient Rome were considered at-risk for the disease because of the favourable conditions present for malaria vectors. This included areas such as southern Italy, the island of Sardinia, the Pontine Marshes, the lower regions of coastal Etruria and the city of Rome along the Tiber. The presence of stagnant water in these places was preferred by mosquitoes for breeding grounds. Irrigated gardens, swamp-like grounds, run-off from agriculture, and drainage problems from road construction led to the increase of standing water.<ref name="Hays-2005"/>
Malaria is not referenced in the medical books of the Mayans or Aztecs. Despite this, antibodies against malaria have been detected in some South American mummies, indicating that some malaria strains in the Americas might have a pre-Columbian origin.<ref>Template:Cite journal</ref> European settlers and the West Africans they enslaved likely brought malaria to the Americas starting in the 16th century.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Scientific studies on malaria made their first significant advance in 1880, when Charles Louis Alphonse Laveran—a French army doctor working in the military hospital of Constantine in Algeria—observed parasites inside the red blood cells of infected people for the first time.<ref>Template:Cite journal</ref> He, therefore, proposed that malaria is caused by this organism, the first time a protist was identified as causing disease.<ref name="The Nobel Foundation"/> For this and later discoveries, he was awarded the 1907 Nobel Prize for Physiology or Medicine. A year later, Carlos Finlay, a Cuban doctor treating people with yellow fever in Havana, provided strong evidence that mosquitoes were transmitting disease to and from humans.<ref name="Tan-2008"/> This work followed earlier suggestions by Josiah C. Nott,<ref name="Chernin-1983"/> and work by Sir Patrick Manson, the "father of tropical medicine", on the transmission of filariasis.<ref name="Chernin-1977"/>
In April 1894, a Scottish physician, Sir Ronald Ross, visited Sir Patrick Manson at his house on Queen Anne Street, London. This visit was the start of four years of collaboration and fervent research that culminated in 1897 when Ross, who was working in the Presidency General Hospital in Calcutta, proved the complete life-cycle of the malaria parasite in mosquitoes.<ref name="Cox-2010" /> He thus proved that the mosquito was the vector for malaria in humans by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds.<ref name="Cox-2010" /> For this work, Ross received the 1902 Nobel Prize in Medicine. After resigning from the Indian Medical Service, Ross worked at the newly established Liverpool School of Tropical Medicine and directed malaria-control efforts in Egypt, Panama, Greece and Mauritius.<ref name="CDC Malaria website"/> The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed in 1900. Its recommendations were implemented by William C. Gorgas in the health measures undertaken during construction of the Panama Canal. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against the disease.<ref name="Simmons-1979"/>
In 1896, Amico Bignami discussed the role of mosquitoes in malaria.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 1898, Bignami, Giovanni Battista Grassi and Giuseppe Bastianelli succeeded in showing experimentally the transmission of malaria in humans, using infected mosquitoes to contract malaria themselves which they presented in November 1898 to the Accademia dei Lincei.<ref name="Cox-2010">Template:Cite journal</ref>
The first effective treatment for malaria came from the bark of cinchona tree, which contains quinine. This tree grows on the slopes of the Andes, mainly in Peru. The indigenous peoples of Peru made a tincture of cinchona to control fever. Its effectiveness against malaria was found and the Jesuits introduced the treatment to Europe around 1640; by 1677, it was included in the London Pharmacopoeia as an antimalarial treatment.<ref name="Kaufman-2005"/> It was not until 1820 that the active ingredient, quinine, was extracted from the bark, isolated and named by the French chemists Pierre Joseph Pelletier and Joseph Bienaimé Caventou.<ref name="Pelletier-1820"/><ref name="Kyle-1974"/>
Quinine was the predominant malarial medication until the 1920s when other medications began to appear. In the 1940s, chloroquine replaced quinine as the treatment of both uncomplicated and severe malaria until resistance supervened, first in Southeast Asia and South America in the 1950s and then globally in the 1980s.<ref name="Achan-2011"/>
The medicinal value of Artemisia annua has been used by Chinese herbalists in traditional Chinese medicines for 2,000 years.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> In 1596, Li Shizhen recommended tea made from qinghao specifically to treat malaria symptoms in his "Compendium of Materia Medica", however the efficacy of tea, made with A. annua, for the treatment of malaria is dubious, and is discouraged by the World Health Organization (WHO).<ref>Template:Cite bookTemplate:Page needed</ref><ref>Template:Cite journal</ref> Artemisinins, discovered by Chinese scientist Tu Youyou and colleagues in the 1970s from the plant Artemisia annua, became the recommended treatment for P. falciparum malaria, administered in severe cases in combination with other antimalarials.<ref name="Hsu-2006"/> Tu says she was influenced by a traditional Chinese herbal medicine source, The Handbook of Prescriptions for Emergency Treatments, written in 340 by Ge Hong.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> For her work on malaria, Tu Youyou received the 2015 Nobel Prize in Physiology or Medicine.<ref name="NobelPrize.org">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Plasmodium vivax was used between 1917 and the 1940s for malariotherapy—deliberate injection of malaria parasites to induce a fever to combat certain diseases such as tertiary syphilis. In 1927, the inventor of this technique, Julius Wagner-Jauregg, received the Nobel Prize in Physiology or Medicine for his discoveries. The technique was dangerous, killing about 15% of patients, so it is no longer in use.<ref name="Vogel-2013"/>
The first pesticide used for indoor residual spraying was DDT.<ref name="US CDC-2010a"/> Although it was initially used exclusively to combat malaria, its use quickly spread to agriculture. In time, pest control, rather than disease control, came to dominate DDT use, and this large-scale agricultural use led to the evolution of pesticide-resistant mosquitoes in many regions. The DDT resistance shown by Anopheles mosquitoes can be compared to antibiotic resistance shown by bacteria. During the 1960s, awareness of the negative consequences of its indiscriminate use increased, ultimately leading to bans on agricultural applications of DDT in many countries in the 1970s.<ref name="van den Berg-2009"/> Before DDT, malaria was successfully eliminated or controlled in tropical areas like Brazil and Egypt by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larval stages, for example by applying the highly toxic arsenic compound Paris Green to places with standing water.<ref name="Killeen-2002"/>
NamesEdit
Various types of malaria have been called by the names below:Template:Citation needed
| Name | Pathogen | Notes |
|---|---|---|
| algid malaria<ref>Template:Cite journal</ref> | Plasmodium falciparum | severe malaria affecting the cardiovascular system and causing chills and circulatory shock |
| bilious malaria | Plasmodium falciparum | severe malaria affecting the liver and causing vomiting and jaundice |
| cerebral malaria | Plasmodium falciparum | severe malaria affecting the cerebrum |
| congenital malaria | various plasmodia | Plasmodium introduced from the mother via the fetal circulation |
| pernicious malaria | Plasmodium falciparum | severe malaria leading to grave illness |
| malignant malaria | Plasmodium falciparum | severe malaria leading to death |
| falciparum malaria, Plasmodium falciparum malaria, | Plasmodium falciparum | |
| ovale malaria, Plasmodium ovale malaria | Plasmodium ovale | |
| quartan malaria, malariae malaria, Plasmodium malariae malaria | Plasmodium malariae | paroxysms every fourth day (quartan), counting the day of occurrence as the first day |
| quotidian malaria | Plasmodium falciparum, Plasmodium vivax, Plasmodium knowlesi | paroxysms daily (quotidian) |
| tertian malaria | Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax | paroxysms every third day (tertian), counting the day of occurrence as the first |
| transfusion malaria | various plasmodia | Plasmodium introduced by blood transfusion, needle sharing, or needlestick injury |
| vivax malaria, Plasmodium vivax malaria | Plasmodium vivax |
Eradication effortsEdit
Malaria has been successfully eliminated or significantly reduced in certain areas, but not globally. Malaria was once common in the United States, but the US eliminated malaria from most parts of the country in the early 20th century using vector control programs, which combined the monitoring and treatment of infected humans, draining of wetland breeding grounds for agriculture and other changes in water management practices, and advances in sanitation, including greater use of glass windows and screens in dwellings.<ref name="Meade-2010"/> The use of the pesticide DDT and other means eliminated malaria from the remaining pockets in southern states of the US in the 1950s, as part of the National Malaria Eradication Program.<ref name="Williams-1963"/> Most of Europe, North America, Australia, North Africa and the Caribbean, and parts of South America, Asia and Southern Africa have also eliminated malaria.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The WHO defines "elimination" (or "malaria-free") as having no domestic transmission (indigenous cases) for the past three years. They also define "pre-elimination" and "elimination" stages when a country has fewer than 5 or 1, respectively, cases per 1000 people at risk per year. In 2021, the total of international and national funding for malaria control and elimination was $3.5 billion—only half of what is estimated to be needed.<ref name="UNICEF DATA-2"/> According to UNICEF, to achieve the goal of a malaria-free world, annual funding would need to more than double to reach the US$6.8 billion target.<ref name="UNICEF DATA-2" />
In parts of the world with rising living standards, the elimination of malaria was often a collateral benefit of the introduction of window screens and improved sanitation.<ref name="Gladwell-2001"/> A variety of usually simultaneous interventions represents best practice. These include antimalarial drugs to prevent or treat infection; improvements in public health infrastructure to diagnose, sequester and treat infected individuals; bednets and other methods intended to keep mosquitoes from biting humans; and vector control strategies<ref name="World Health Organization-2009">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> such as larvaciding with insecticides, ecological controls such as draining mosquito breeding grounds or introducing fish to eat larvae and indoor residual spraying (IRS) with insecticides.
Initial WHO program (1955–1969)Edit
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In 1955 the WHO launched the Global Malaria Eradication Program (GMEP).<ref name="Duintjer-2009">Template:Cite journal</ref> The program relied largely on DDT for mosquito control and rapid diagnosis and treatment to break the transmission cycle.<ref>Template:Cite journal</ref> The program eliminated the disease in "North America, Europe, the former Soviet Union",<ref name="Sadasivaiah-2007"/> and in "Taiwan, much of the Caribbean, the Balkans, parts of northern Africa, the northern region of Australia, and a large swath of the South Pacific"<ref name="Gladwell-2001">Template:Cite news</ref> and dramatically reduced mortality in Sri Lanka and India.<ref name="Harrison-1978"/>
However, failure to sustain the program, increasing mosquito tolerance to DDT, and increasing parasite tolerance led to a resurgence. In many areas early successes partially or completely reversed, and in some cases rates of transmission increased.<ref name="Chapin-1981">Template:Cite journal</ref> Experts tie malarial resurgence to multiple factors, including poor leadership, management and funding of malaria control programs; poverty; civil unrest; and increased irrigation. The evolution of resistance to first-generation drugs (e.g. chloroquine) and to insecticides exacerbated the situation.<ref name="van den Berg-2008">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Feachem-2007">Template:Cite journal</ref> The program succeeded in eliminating malaria only in areas with "high socio-economic status, well-organized healthcare systems, and relatively less intensive or seasonal malaria transmission".<ref name="Sadasivaiah-2007">Template:Cite journal</ref>
For example, in Sri Lanka, the program reduced cases from about one million per year before spraying to just 18 in 1963<ref>Template:Cite book</ref><ref>Template:Cite news</ref> and 29 in 1964. Thereafter the program was halted to save money and malaria rebounded to 600,000 cases in 1968 and the first quarter of 1969. The country resumed DDT vector control but the mosquitoes had evolved resistance in the interim, presumably because of continued agricultural use. The program switched to malathion, but despite initial successes, malaria continued its resurgence into the 1980s.<ref name="Harrison-1978">Template:Cite book</ref><ref>Template:Cite journal</ref>
Due to vector and parasite resistance and other factors, the feasibility of eradicating malaria with the strategy used at the time and resources available led to waning support for the program.<ref name="Nájera-2011">Template:Cite journal</ref> WHO suspended the program in 1969<ref name="Duintjer-2009"/><ref name="Nájera-2011"/> and attention instead focused on controlling and treating the disease. Spraying programs (especially using DDT) were curtailed due to concerns over safety and environmental effects, as well as problems in administrative, managerial and financial implementation.<ref name="Chapin-1981"/> Efforts shifted from spraying to the use of bednets impregnated with insecticides and other interventions.<ref name="Sadasivaiah-2007"/><ref name="Rogan-2005">Template:Cite journal</ref>
After 1969Edit
Target 6C of the Millennium Development Goals included reversal of the global increase in malaria incidence by 2015, with specific targets for children under five years old.<ref name="Sato-2021">Template:Cite journal</ref> Since 2000, support for malaria eradication increased, although some actors in the global health community (including voices within the WHO) view malaria eradication as a premature goal and suggest that the establishment of strict deadlines for malaria eradication may be counterproductive as they are likely to be missed.<ref>Template:Cite journal</ref> One of the targets of Goal 3 of the UN's Sustainable Development Goals is to end the malaria epidemic in all countries by 2030.
In 2006, the organization Malaria No More set a public goal of eliminating malaria from Africa by 2015, and the organization claimed they planned to dissolve if that goal was accomplished. In 2007, World Malaria Day was established by the 60th session of the World Health Assembly. As of 2018, they are still functioning.<ref name="Strom-2011"/>
Template:As of, The Global Fund to Fight AIDS, Tuberculosis, and Malaria has distributed 230 million insecticide-treated nets intended to stop mosquito-borne transmission of malaria.<ref name="Global Fund"/> The U.S.-based Clinton Foundation has worked to manage demand and stabilize prices in the artemisinin market.<ref name="Schoofs-2008"/> Other efforts, such as the Malaria Atlas Project, focus on analysing climate and weather information required to accurately predict malaria spread based on the availability of habitat of malaria-carrying parasites.<ref name="Guerra-2007"/> The Malaria Policy Advisory Committee (MPAC) of the World Health Organization (WHO) was formed in 2012, "to provide strategic advice and technical input to WHO on all aspects of malaria control and elimination".<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
In 2015 the WHO targeted a 90% reduction in malaria deaths by 2030,<ref name="Fletcher-2019" /> and Bill Gates said in 2016 that he thought global eradication would be possible by 2040.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> According to the WHO's World Malaria Report 2015, the global mortality rate for malaria fell by 60% between 2000 and 2015. The WHO targeted a further 90% reduction between 2015 and 2030,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> with a 40% reduction and eradication in 10 countries by 2020.Template:Sfn However, the 2020 goal was missed with a slight increase in cases compared to 2015.<ref name="WHO-2020">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Additionally, UNICEF reported that the number of malaria deaths for all ages increased by 10% between 2019 and 2020, in part due to service disruptions related to the COVID-19 pandemic, before experiencing a minor decline in 2021.<ref name="UNICEF DATA-2"/>
Before 2016, the Global Fund against HIV/AIDS, Tuberculosis and Malaria had provided 659 million ITN (insecticide treated bed nets), organise support and education to prevents malaria. The challenges are high due to the lack of funds, the fragile health structure and the remote indigenous population that could be hard to reach and educate. Most of indigenous population rely on self-diagnosis, self-treatment, healer, and traditional medicine. The WHO applied for fund to the Gates Foundation which favour the action of malaria eradication in 2007.<ref>Template:Cite journal</ref> Six countries, the United Arab Emirates, Morocco, Armenia, Turkmenistan, Kyrgyzstan, and Sri Lanka managed to have no endemic cases of malaria for three consecutive years and certified malaria-free by the WHO despite the stagnation of the funding in 2010.<ref name="Sato-2021"/> The funding is essential to finance the cost of medication and hospitalisation cannot be supported by the poor countries where the disease is widely spread. The goal of eradication has not been met; nevertheless, the decrease rate of the disease is considerable.
While 31 out of 92 endemic countries were estimated to be on track with the WHO goals for 2020, 15 countries reported an increase of 40% or more between 2015 and 2020.<ref name="WHO-2020"/> Between 2000 and 30 June 2021, twelve countries were certified by the WHO as being malaria-free. Argentina and Algeria were declared free of malaria in 2019.<ref name="WHO-2020"/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> El Salvador and China were declared malaria-free in the first half of 2021.<ref>Template:Cite Q</ref><ref name="World Health Organization-2021b">Template:Cite Q.</ref>
Regional disparities were evident: Southeast Asia was on track to meet WHO's 2020 goals, while Africa, Americas, Eastern Mediterranean and West Pacific regions were off-track.<ref name="WHO-2020"/> The six Greater Mekong Subregion countries aim for elimination of P. falciparum transmitted malaria by 2025 and elimination of all malaria by 2030, having achieved a 97% and 90% reduction of cases respectively since 2000.<ref name="WHO-2020"/> Ahead of World Malaria Day, 25 April 2021, WHO named 25 countries in which it is working to eliminate malaria by 2025 as part of its E-2025 initiative.<ref>Template:Cite Q</ref>
A major challenge to malaria elimination is the persistence of malaria in border regions, making international cooperation crucial.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
In 2018, WHO announced that Paraguay was free of malaria, after a national malaria eradication effort that began in 1950.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
In March 2023, the WHO certified Azerbaijan and Tajikistan as malaria-free,<ref name="WHO-2023a">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and Belize in June 2023.<ref name="WHO-2023b">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Cabo Verde, the latest country to eradicate Malaria, was certified in January 2024, bringing the total number of countries and territories certified malaria-free to 44.<ref name="WHO-2024">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In October 2024, the WHO certified Egypt to be malaria-free.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Potential eradication of malaria by year 2050Edit
Experts say that malaria could be eliminated as wild disease of humans by the year 2050. World class experts (41 of them) in fields such as malariology, biomedicine, economics and health policy advocated more funding, a central data repository for dealing with local outbreaks of malaria, and training the workers needed to carry out the plan. Details are published in The Lancet. The report refers to current knowledge, recent research and financial matters to describe a respectable plan.<ref>Malaria could be eradicated by 2050, say global experts| https://www.bmj.com/content/366/bmj.l5501</ref>
The number of countries in which malaria was endemic was reduced from 200 to 86 in the years from 1900 to 2017. A further reduction by another 20 countries occurred by 2020. In light of the indication of possible practical accomplishment, countries and regions are planning further progress. Through the use of optimal diagnostic techniques, effective treatment and vector reduction the world should be nearly free of malaria by 2050. This will require technical improvements in organizational efficiency and more money.<ref>MALARIA ERADICATION WITHIN A GENERATION| https://live-malariaeradicationcommission.pantheonsite.io/sites/default/files/overview-brief-english.pdf</ref>
Society and cultureEdit
Economic consequencesEdit
Malaria is not just a disease commonly associated with poverty; some evidence suggests that it is also a cause of poverty and a major hindrance to economic development.<ref name="Gollin-2007"/><ref name="Worrall-2005"/> Although tropical regions are most affected, malaria's furthest influence reaches into some temperate zones that have extreme seasonal changes. The disease has been associated with major negative economic effects on regions where it is widespread. During the late 19th and early 20th centuries, it was a major factor in the slow economic development of the American southern states.<ref name="Humphreys-2001"/>
A comparison of average per capita GDP in 1995, adjusted for parity of purchasing power, between countries with malaria and countries without malaria gives a fivefold difference (US$1,526 versus US$8,268). In the period 1965 to 1990, countries where malaria was common had an average per capita GDP that increased only 0.4% per year, compared to 2.4% per year in other countries.<ref name="Sachs-2002"/>
Poverty can increase the risk of malaria since those in poverty do not have the financial capacities to prevent or treat the disease. In its entirety, the economic consequences of malaria has been estimated to cost Africa US$12 billion every year. This includes costs of health care, working days lost due to sickness, days lost in education, decreased productivity due to brain damage from cerebral malaria, and loss of investment and tourism.<ref name="Greenwood-2005"/> The disease has a heavy burden in some countries, where it may be responsible for 30–50% of hospital admissions, up to 50% of outpatient visits, and up to 40% of public health spending.<ref name="WHO-2003"/>
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Cerebral malaria is one of the leading causes of neurological disabilities in African children.<ref name="Idro-2010"/> Studies comparing cognitive functions before and after treatment for severe malarial illness continued to show significantly impaired school performance and cognitive abilities even after recovery.<ref name="Fernando-2010"/> Consequently, severe and cerebral malaria have far-reaching socioeconomic consequences that extend beyond the immediate effects of the disease.<ref name="Ricci-2012"/>
Counterfeit and substandard drugsEdit
Sophisticated counterfeits have been found in several Asian countries such as Cambodia,<ref name="Lon-2006"/> China,<ref name="Newton-2008"/> Indonesia, Laos, Thailand, and Vietnam, and are a major cause of avoidable death in those countries.<ref name="Newton-2006"/> The WHO said that studies indicate that up to 40% of artesunate-based malaria medications are counterfeit, especially in the Greater Mekong region. They have established a rapid alert system to rapidly report information about counterfeit drugs to relevant authorities in participating countries.<ref name="Parry-2005"/> There is no reliable way for doctors or lay people to detect counterfeit drugs without help from a laboratory. Companies are attempting to combat the persistence of counterfeit drugs by using new technology to provide security from source to distribution.<ref name="Gautam-2009"/>
Another clinical and public health concern is the proliferation of substandard antimalarial medicines resulting from inappropriate concentration of ingredients, contamination with other drugs or toxic impurities, poor quality ingredients, poor stability and inadequate packaging.<ref name="Caudron-2008"/> A 2012 study demonstrated that roughly one-third of antimalarial medications in Southeast Asia and Sub-Saharan Africa failed chemical analysis, packaging analysis, or were falsified.<ref name="Nayyar-2012"/>
WarEdit
Throughout history, the contraction of malaria has played a prominent role in the fates of government rulers, nation-states, military personnel, and military actions.<ref name="Russell-2009"/> In 1910, Nobel Prize in Medicine-winner Sir Ronald Ross (himself a malaria survivor), published a book titled The Prevention of Malaria that included a chapter titled "The Prevention of Malaria in War". The chapter's author, Colonel C. H. Melville, Professor of Hygiene at Royal Army Medical College in London, addressed the prominent role that malaria has historically played during wars: "The history of malaria in war might almost be taken to be the history of war itself, certainly the history of war in the Christian era. ... It is probably the case that many of the so-called camp fevers, and probably also a considerable proportion of the camp dysentery, of the wars of the sixteenth, seventeenth and eighteenth centuries were malarial in origin."<ref name="Melville-1910"/> In British-occupied India the cocktail gin and tonic may have come about as a way of taking quinine, known for its antimalarial properties.<ref>Template:Cite book</ref>
The Scottish attempt to build a canal near what is now the Panamanian one was largely defeated by malaria. Starting with the establishment of "New Caledonia", The Darièn Gap Project drained the kingdom — not yet part of the United Kingdom — of most of its wealth. The cost of the bail-out from London was the independence of Scotland.
Malaria was the most significant health hazard encountered by U.S. troops in the South Pacific during World War II, where about 500,000 men were infected.<ref name="Bray-2004"/> According to Joseph Patrick Byrne, "Sixty thousand American soldiers died of malaria during the African and South Pacific campaigns."<ref name="Byrne-2008"/>
Significant financial investments have been made to procure existing and create new antimalarial agents. During World War I and World War II, inconsistent supplies of the natural antimalaria drugs cinchona bark and quinine prompted substantial funding into research and development of other drugs and vaccines. American military organisations conducting such research initiatives include the Navy Medical Research Center, Walter Reed Army Institute of Research, and the U.S. Army Medical Research Institute of Infectious Diseases of the US Armed Forces.<ref name="Kakkilaya-2006"/>
Additionally, initiatives have been founded such as Malaria Control in War Areas (MCWA), established in 1942, and its successor, the Communicable Disease Center (now known as the Centers for Disease Control and Prevention, or CDC) established in 1946. According to the CDC, MCWA "was established to control malaria around military training bases in the southern United States and its territories, where malaria was still problematic".<ref name="US CDC-2010c"/>
ResearchEdit
The Malaria Eradication Research Agenda (malERA) initiative was a consultative process to identify which areas of research and development (R&D) must be addressed for worldwide eradication of malaria.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
MedicationsEdit
Malaria parasites contain apicoplasts, organelles related to the plastids found in plants, complete with their own genomes. These apicoplasts are thought to have originated through the endosymbiosis of algae and play a crucial role in various aspects of parasite metabolism, such as fatty acid biosynthesis. Over 400 proteins have been found to be produced by apicoplasts and these are now being investigated as possible targets for novel antimalarial drugs.<ref name="Kalanon-2010"/>
With the onset of drug-resistant Plasmodium parasites, new strategies are being developed to combat the widespread disease. One such approach lies in the introduction of synthetic pyridoxal-amino acid adducts, which are taken up by the parasite and ultimately interfere with its ability to create several essential B vitamins.<ref name="Müller-2010"/><ref name="Du-2011"/> Antimalarial drugs using synthetic metal-based complexes are attracting research interest.<ref name="Biot-2012"/><ref name="Roux-2012"/>
- (+)-SJ733: Part of a wider class of experimental drugs called spiroindolone. It inhibits the ATP4 protein of infected red blood cells that cause the cells to shrink and become rigid like the aging cells. This triggers the immune system to eliminate the infected cells from the system as demonstrated in a mouse model. As of 2014, a Phase 1 clinical trial to assess the safety profile in human is planned by the Howard Hughes Medical Institute.<ref name="John-2014">{{#invoke:citation/CS1|citation
|CitationClass=web }}</ref>
- NITD246 and NITD609: Also belonged to the class of spiroindolone and target the ATP4 protein.<ref name="John-2014"/>
On the basis of molecular docking outcomes, compounds 3j, 4b, 4h, 4m were exhibited selectivity towards PfLDH. The post docking analysis displayed stable dynamic behavior of all the selected compounds compared to Chloroquine. The end state thermodynamics analysis stated 3j compound as a selective and potent PfLDH inhibitor.<ref name="Singh-2021">Template:Cite journal</ref>
New targetsEdit
Targeting Plasmodium liver-stage parasites selectively is emerging as an alternative strategy in the face of resistance to the latest frontline combination therapies against blood stages of the parasite.<ref name="Stanway-2019">Template:Cite journal</ref>
In research conducted in 2019, using experimental analysis with knockout (KO) mutants of Plasmodium berghei, the authors were able to identify genes that are potentially essential in the liver stage. Moreover, they generated a computational model to analyse pre–erytrocytic development and liver–stage metabolism. Combining both methods they identified seven metabolic subsystems that become essential compared to the blood stage. Some of these metabolic pathways are fatty acid synthesis and elongation, tricarboxylic acid, amino acid and heme metabolism among others.<ref name="Stanway-2019"/>
Specifically, they studied three subsystems: fatty acid synthesis and elongation, and amino sugar biosynthesis. For the first two pathways they demonstrated a clear dependence of the liver stage on its own fatty acid metabolism.<ref name="Stanway-2019"/>
They proved for the first time the critical role of amino sugar biosynthesis in the liver stage of P. berghei. The uptake of N–acetyl–glucosamine appears to be limited in the liver stage, being its synthesis needed for the parasite development.<ref name="Stanway-2019"/>
These findings and the computational model provide a basis for the design of antimalarial therapies targeting metabolic proteins.<ref name="Stanway-2019"/><ref>Template:Cite journal</ref>
Genomic researchEdit
The genome of Plasmodium falciparum was sequenced and published in the year 2002.<ref>Template:Cite journal</ref>
A species of malaria plasmodium tends to have rather polymorphic antigens which can serve as immune system targets. Some searches of P. falciparum genes for hotspots of encoded variations found sections of genes that when tested proved to encode for antigens. When such antigens are used for vaccine targets a strain of plasmodium with a different allele for the antigen can sometimes escape the immune response stimulated by the vaccine.<ref>Malaria Genomics, Vaccine Development, and Microbiome| https://www.mdpi.com/2076-0817/12/8/1061</ref>
Two related viruses, MaRNAV-1 and MaRNAV-2 in Plasmodium vivax and in avian Leucocytozoon respectively, were found through RNA-Sequencing of blood. The finding of a virus infecting a human malaria plasmodium is a first discovery of its kind. It should lead to better understanding of malaria biology.<ref>Template:Cite journal</ref>
OtherEdit
A non-chemical vector control strategy involves genetic manipulation of malaria mosquitoes. Advances in genetic engineering technologies make it possible to introduce foreign DNA into the mosquito genome and either decrease the lifespan of the mosquito, or make it more resistant to the malaria parasite. Sterile insect technique is a genetic control method whereby large numbers of sterile male mosquitoes are reared and released. Mating with wild females reduces the wild population in the subsequent generation; repeated releases eventually eliminate the target population.<ref name="Raghavendra-2011"/>
Genomics is central to malaria research. With the sequencing of P. falciparum, one of its vectors Anopheles gambiae, and the human genome, the genetics of all three organisms in the malaria life cycle can be studied.<ref name="Aultman-2002"/> Another new application of genetic technology is the ability to produce genetically modified mosquitoes that do not transmit malaria, potentially allowing biological control of malaria transmission.<ref name="Ito-2002"/>
In one study, a genetically modified strain of Anopheles stephensi was created that no longer supported malaria transmission, and this resistance was passed down to mosquito offspring.<ref>Template:Cite journal</ref>
Gene drive is a technique for changing wild populations, for instance to combat or eliminate insects so they cannot transmit diseases (in particular mosquitoes in the cases of malaria,<ref name="Imperial College-2021">Template:Cite news</ref> zika,<ref name="Flam-2016">Template:Cite news</ref> dengue and yellow fever).<ref name="Fletcher-2019">Template:Cite news</ref>
In a study conducted in 2015, researchers observed a specific interaction between malaria and co-infection with the nematode Nippostrongylus brasiliensis, a pulmonary migrating helminth, in mice.<ref name="Griffiths-2015">Template:Cite journal</ref> The co-infection was found to reduce the virulence of the Plasmodium parasite, the causative agent of malaria. This reduction was attributed to the nematode infection causing increased destruction of erythrocytes, or red blood cells. Given that Plasmodium has a predilection for older host erythrocytes, the increased erythrocyte destruction and ensuing erythropoiesis result in a predominantly younger erythrocyte population, which in turn leads to a decrease in Plasmodium population.<ref name="Griffiths-2015" /> Notably, this effect appears to be largely independent of the host's immune control of Plasmodium.
Finally, a review article published in December 2020 noted a correlation between malaria-endemic regions and COVID-19 case fatality rates.<ref name="Arshad-2020">Template:Cite journal</ref> The study found that, on average, regions where malaria is endemic reported lower COVID-19 case fatality rates compared to regions without endemic malaria.
In 2017, a bacterial strain of the genus Serratia was genetically modified to prevent malaria in mosquitos<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> and in 2023, it has been reported that the bacterium Delftia tsuruhatensis naturally prevents the development of malaria by secreting a molecule called Harmane.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite news</ref>
Other avenue that can contribute to understanding of malaria transmission, is the source of meal for the vector when they have the parasites. Its known that plant sugars are the primary source of nutrients for survival of adult mosquitoes,<ref>Template:Cite journal</ref> therefore utilising this link for management of the vector will contribute in mitigating malaria transmission.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
In a 2018 study of 400 Kenyan school aged children, researchers were able to diagnose malaria with 100% sensitivity based on volatile biomarkers in the skin (molecules that cause odors). And the volatile biomarker signature of those with symptomatic and asymptomatic disease differed significantly. Thus introducing a possible new diagnostic test for the disease.<ref name="De Moraes 2018">Template:Cite journal</ref>
Other animalsEdit
While none of the main four species of malaria parasite that cause human infections are known to have animal reservoirs,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> P. knowlesi is known to infect both humans and non-human primates.<ref name="Collins-2012"/> Other non-human primate malarias (particularly P. cynomolgi and P. simium) have also been found to have spilled over into humans.<ref>Template:Cite journal</ref> Nearly 200 Plasmodium species have been identified that infect birds, reptiles, and other mammals,<ref name="Rich-2006" /> and about 30 of them naturally infect non-human primates.<ref name="Baird-2009" /> Some malaria parasites of non-human primates (NHP) serve as model organisms for human malarial parasites, such as P. coatneyi (a model for P. falciparum) and P. cynomolgi (a model for P. vivax). Diagnostic techniques used to detect parasites in NHP are similar to those employed for humans.<ref name="Ameri-2010" /> Malaria parasites that infect rodents are widely used as models in research, such as P. berghei.<ref name="Mlambo-2008"/> Avian malaria primarily affects species of the order Passeriformes, and poses a substantial threat to birds of Hawaii, the Galapagos, and other archipelagoes. The parasite P. relictum is known to play a role in limiting the distribution and abundance of endemic Hawaiian birds. Global warming is expected to increase the prevalence and global distribution of avian malaria, as elevated temperatures provide optimal conditions for parasite reproduction.<ref name="Lapointe-2012"/>
ReferencesEdit
SourcesEdit
Further readingEdit
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External linksEdit
Template:Sister project links Template:Offline
- WHO site on malaria (Template:Webarchive)
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- PAHO site on malaria (Template:Webarchive)
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