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Malaria is a mosquito-borne infectious disease that affects and Anopheles mosquitoes. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and . In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. The mosquitoes themselves are harmed by malaria, causing reduced lifespans in those infected by it.
Malaria is caused by protozoa of the genus Plasmodium. It is spread exclusively through bites of infected female Anopheles mosquitoes. The mosquito bite introduces the from the mosquito's saliva into the blood. The parasites travel to the liver, where they mature and reproduce. Five species of Plasmodium commonly infect humans. The three species associated with more severe cases are P. falciparum (which is responsible for the vast majority of malaria deaths), Plasmodium vivax, and P. knowlesi (a simian malaria that spills over into thousands of people a year). Plasmodium ovale and P. malariae generally cause a milder form of malaria. Malaria is typically diagnosed by the histology of blood using , or with antigen-based rapid diagnostic tests. 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.
The risk of disease can be reduced by preventing mosquito bites through the use of and or with Mosquito control such as spraying and draining standing water. Several medications are available to prevent malaria for travellers in areas where the disease is common. 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. As of 2023, two have been endorsed by the World Health Organization. The recommended treatment for malaria is a combination of antimalarial medications that includes artemisinin. The second medication may be either mefloquine (noting first its potential toxicity and the possibility of death), lumefantrine, or sulfadoxine/pyrimethamine. (2025). 9789241547925, World Health Organization. ISBN 9789241547925 Quinine, along with doxycycline, may be used if artemisinin is not available. In areas where the disease is common, malaria should be confirmed if possible before treatment is started due to concerns of increasing drug resistance. 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.
The disease is widespread in the Tropics and subtropical regions that exist in a broad band around the equator. (2025). 9780198816805 ISBN 9780198816805 This includes much of sub-Saharan Africa, Asia, and Latin America. In 2023, some 263 million cases of malaria worldwide resulted in an estimated 597,000 deaths. 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. According to UNICEF, nearly every minute, a child under five died of malaria in 2021, and "many of these deaths are preventable and treatable". Malaria is commonly associated with poverty and has a significant negative effect on economic development. 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. The malaria caseload in India decreased by 69% from 6.4 million cases in 2017 to two million cases in 2023. Similarly, the estimated malaria deaths decreased from 11,100 to 3,500 (a 68% decrease) in the same period.
Accessed 18 Nov. 2024.
Initial manifestations of the disease—common to infection with all malaria parasite species—are similar to flu, and can resemble other conditions such as sepsis, gastroenteritis, and . The presentation may include headache, fever, shivering, arthralgia, vomiting, hemolytic anemia, jaundice, hemoglobinuria, Retinopathy, and .
The classic symptom of malaria is paroxysmal attacks—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.
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. Travellers taking preventative malaria medications may develop symptoms once they stop taking the drugs.
Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection. 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, , or coma.
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. An Splenomegaly, hepatomegaly or both of these, severe headache, hypoglycemia, and hemoglobinuria with kidney failure may occur. Complications may include spontaneous bleeding, coagulopathy, and shock.Davidson's Principles and Practice of Medicine/21st/351
Cerebral malaria can bring about death within forty-eight hours of the first symptoms of the infection being evident.
Malaria during pregnancy can cause , infant mortality, miscarriage, and low birth weight, particularly in P. falciparum infection, but also with P. vivax.
The Anopheles mosquitos initially get infected by Plasmodium by taking a blood meal from a previously Plasmodium infected person or animal. Parasites are then typically introduced by the bite of an infected Anopheles mosquito. Some of these inoculated parasites, called "", probably remain in the skin, but others travel in the bloodstream to the liver, where they invade . They grow and divide in the liver for 2–10 days, with each infected hepatocyte eventually harboring up to 40,000 parasites. The infected hepatocytes break down, releasing these invasive Plasmodium cells, called "", 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. 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. 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 "". 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. Once inside a mosquito, the gametocytes undergo sexual reproduction, and eventually form daughter sporozoites that migrate to the mosquito's to be injected into a new host when the mosquito bites.
The liver infection causes no symptoms; all symptoms of malaria result from the infection of red blood cells. Symptoms develop once there are more than around 100,000 parasites per milliliter of blood. 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. The destruction of red blood cells during infection often results in anemia, exacerbated by reduced production of new red blood cells during infection.
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. However, in Africa, due to the extensive use of bed nets, they began to bite earlier, before bed-net time. Malaria parasites can also be transmitted by blood transfusions, although this is rare.
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. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.
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.
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. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in P. vivax infections, although their existence in P. ovale is uncertain.
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 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. The blockage of the microvasculature causes symptoms such as those in placental malaria. Sequestered red blood cells can breach the blood–brain barrier and cause cerebral malaria.
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 hemoglobin 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.
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%). 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.
Malaria is usually confirmed by the microscopic examination of 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. 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. 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. Microscopic diagnosis is relatively resource intensive, requiring trained personnel, specific equipment and a consistent supply of Microscope slide and stains.
In places where microscopy is unavailable, malaria is diagnosed with RDTs, rapid antigen tests that detect parasite proteins in a fingerstick blood sample. A variety of RDTs are commercially available, targeting the parasite proteins histidine rich protein 2 (HRP2, detects P. falciparum only), lactate dehydrogenase, or aldolase. The HRP2 test is widely used in Africa, where P. falciparum predominates. 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. Additionally, some P. falciparum parasites in the Amazon region lack the HRP2 gene, complicating detection. Some P. falciparum species also have genetic deletions of the genes coding for the HRP2 antigen; leading to possible false negative results. Rapid tests also cannot quantify the parasite burden in a person. RDTs are fast and easily deployed to places without full diagnostic laboratories. However they give considerably less information than microscopy, and sometimes vary in quality from producer to producer and lot to lot.
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.
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.
Prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the Capital cost 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 —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. In 2021, the World Health Organization confirmed that China has eliminated malaria. In 2023, the World Health Organization confirmed that Azerbaijan, Tajikistan, and Belize have eliminated malaria.
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.
In areas of high malaria resistance, piperonyl butoxide (PBO) combined with pyrethroids in mosquito netting is effective in reducing malaria infection rates. Questions remain concerning the durability of PBO on nets as the effect on mosquito mortality was not sustained after twenty washes in experimental trials.
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". 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". Slightly more than half of the households with an ITN had enough of them to protect all members of the household, however.
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. 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.
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. 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.
In some cases, studies have used insecticide-treated (e.g., transfluthrin) or untreated netting to deter mosquito entry. 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. 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. 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.
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.
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). 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. 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. The use of preventive drugs where malaria-bearing mosquitoes are present may encourage the development of partial resistance.
Giving antimalarial drugs to infants through intermittent preventive therapy can reduce the risk of having malaria infection, hospital admission, and anaemia.
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. 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.
Prompt treatment of confirmed cases with artemisinin-based combination therapies (ACTs) may also reduce transmission.
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. The first vaccine, called RTS,S, was approved by European regulators in 2015. As of 2023, two have been licensed for use. Other approaches to combat malaria may require investing more in research and greater primary health care. Continuing surveillance will also be important to prevent the return of malaria in countries where the disease has been eliminated.
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).
Immunity (or, more accurately, immune tolerance) to P. falciparum malaria does occur naturally, but only in response to years of repeated infection. 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. Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have been inadequate on their own. For example, SPf66 was tested extensively in areas where the disease was common in the 1990s, but trials showed it to be insufficiently effective.
As of 2020, the RTS,S vaccine has been shown to reduce the risk of malaria by about 40% in children in Africa.
The R-21/Matrix M malaria vaccine was found to reduce cases of malaria by 75% in areas with seasonal spread and by 68% in areas of year-round spread in children in sub-saharan Africa. The R-21/Matrix M malaria vaccine was endorsed by the WHO for the prevention of malaria in children in 2023.
Germany-based BioNTECH SE is developing an mRNA-based malaria vaccine BNT165 which has recently initiated a Phase 1 study clinicaltrials.gov 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.
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. These two drugs act against blood stages as well, the extent to which they do so still being under investigation.
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). There is limited safety data on the antimalarial drugs in pregnancy.
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. In another systematic review, artemisinin derivatives (artemether and arteether) were as efficacious as quinine in the treatment of cerebral malaria in children. Treatment of severe malaria involves supportive measures that are best done in a critical care unit. This includes the management of hyperpyrexia and the seizures that may result from it. It also includes monitoring for poor breathing effort, low blood sugar, and hypokalemia. Artemisinin derivatives have the same or better efficacy than quinolones in preventing deaths in severe or complicated malaria. Quinine loading dose helps to shorten the duration of fever and increases parasite clearance from the body. There is no difference in effectiveness when using intrarectal quinine compared to intravenous or intramuscular quinine in treating uncomplicated/complicated falciparum malaria. There is insufficient evidence for intramuscular arteether to treat severe malaria. The provision of rectal artesunate before transfer to hospital may reduce the rate of death for children with severe malaria. 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.
Cerebral malaria is the form of severe and complicated malaria with the worst neurological symptoms. There is insufficient data on whether osmotic agents such as mannitol or urea are effective in treating cerebral malaria. Routine phenobarbitone in cerebral malaria is associated with fewer but possibly more deaths. There is no evidence that steroids would bring treatment benefits for cerebral malaria.
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. There is insufficient evidence that iron chelating agents such as deferoxamine and deferiprone improve outcomes of those with malaria falciparum infection.
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.
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When properly treated, people with malaria can usually expect a complete recovery. However, severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease, can reach 20%, even with intensive care and treatment. Over the longer term, developmental impairments have been documented in children who have had episodes of severe malaria. 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.
During childhood, malaria causes anaemia during a period of rapid brain development, and also direct brain damage resulting from cerebral malaria. Some survivors of cerebral malaria have an increased risk of neurological and cognitive deficits, behavioural disorders, and epilepsy. Malaria prophylaxis was shown to improve cognitive function and school performance in when compared to placebo groups.
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 ninety percent of malaria fatalities occur in Sub-Saharan Africa. 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). A 2010 estimate indicated the deadliest countries per population were Burkina Faso, Mozambique and Mali. 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. This effort led to the publication of a map of P. falciparum endemicity in 2010 and an update in 2019. As of 2021, 84 countries have endemic malaria.
The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other. 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. In drier areas, outbreaks of malaria have been predicted with reasonable accuracy by mapping rainfall. 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. In contrast, malaria in Africa is present in both rural and urban areas, though the risk is lower in the larger cities.
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.
Since 1900 there has been substantial change in temperature and rainfall over Africa. 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. 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.
References to the unique periodic fevers of malaria are found throughout history. Ancient Indian physician Sushruta believed that the disease was associated with biting insects, long before the Roman Columella associated the disease with insects from swamps. Hippocrates described periodic fevers, labelling them tertian, quartan, subtertian and quotidian. Malaria may have contributed to the decline of the Roman Empire, and was so pervasive in Rome that it was known as the "Roman fever". 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.
Malaria is not referenced in the medical books of the Maya peoples 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. European settlers and the West Africans they enslaved likely brought malaria to the Americas starting in the 16th century.
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. He, therefore, proposed that malaria is caused by this organism, the first time a protist was identified as causing disease. 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. This work followed earlier suggestions by Josiah C. Nott, and work by Sir Patrick Manson, the "father of tropical medicine", on the transmission of filariasis.
In April 1894, a Scottish physician, 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 Kolkata, proved the complete life-cycle of the malaria parasite in mosquitoes. 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. 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. 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.
In 1896, Amico Bignami discussed the role of mosquitoes in malaria. 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.
The first effective treatment for malaria came from the bark of Cinchona, 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 introduced the treatment to Europe around 1640; by 1677, it was included in the London Pharmacopoeia as an antimalarial treatment. 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.
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.
The medicinal value of Artemisia annua has been used by Chinese herbalists in traditional Chinese medicines for 2,000 years. 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). (2025). 9789241594431, World Health Organization. ISBN 9789241594431 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. 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. For her work on malaria, Tu Youyou received the 2015 Nobel Prize in Physiology or Medicine.
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.
The first pesticide used for indoor residual spraying was DDT. 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. 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.
| severe malaria affecting the cardiovascular system and causing chills and circulatory shock |
| severe malaria affecting the liver and causing vomiting and jaundice |
| severe malaria affecting the cerebrum |
| Plasmodium introduced from the mother via the fetal circulation |
| severe malaria leading to grave illness |
| severe malaria leading to death |
| paroxysms every fourth day (), counting the day of occurrence as the first day |
| paroxysms daily () |
| paroxysms every third day (), counting the day of occurrence as the first |
| Plasmodium introduced by blood transfusion, needle sharing, or needlestick injury |
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. 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; mosquito net and other methods intended to keep mosquitoes from biting humans; and vector control strategies such as larvacide with insecticides, ecological controls such as draining mosquito breeding grounds or introducing fish to eat larvae and indoor residual spraying (IRS) with insecticides.
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. 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. 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".
For example, in Sri Lanka, the program reduced cases from about one million per year before spraying to just 18 in 1963 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.
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. WHO suspended the program in 1969 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. Efforts shifted from spraying to the use of Mosquito net impregnated with insecticides and other interventions.
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.
, The Global Fund to Fight AIDS, Tuberculosis, and Malaria has distributed 230 million insecticide-treated nets intended to stop mosquito-borne transmission of malaria. The U.S.-based Clinton Foundation has worked to manage demand and stabilize prices in the artemisinin market. 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. 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".
In 2015 the WHO targeted a 90% reduction in malaria deaths by 2030, and Bill Gates said in 2016 that he thought global eradication would be possible by 2040. 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, with a 40% reduction and eradication in 10 countries by 2020. However, the 2020 goal was missed with a slight increase in cases compared to 2015. 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.
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. 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. 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. 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. El Salvador and China were declared malaria-free in the first half of 2021..
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. 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. 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.
A major challenge to malaria elimination is the persistence of malaria in border regions, making international cooperation crucial.
In 2018, WHO announced that Paraguay was free of malaria, after a national malaria eradication effort that began in 1950.
In March 2023, the WHO certified Azerbaijan and Tajikistan as malaria-free, and Belize in June 2023. Cabo Verde was certified in January 2024, bringing the total number of countries and territories certified malaria-free to 44. In October 2024, the WHO certified Egypt to be malaria-free.
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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.
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. 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.
Cerebral malaria is one of the leading causes of neurological disabilities in African children. 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. Consequently, severe and cerebral malaria have far-reaching socioeconomic consequences that extend beyond the immediate effects of the disease.
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. 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.
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. According to Joseph Patrick Byrne, "Sixty thousand American soldiers died of malaria during the African and South Pacific campaigns."
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.
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".
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 , which are taken up by the parasite and ultimately interfere with its ability to create several essential . Antimalarial drugs using synthetic metal-based complexes are attracting research interest.
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.
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.
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.
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.
These findings and the computational model provide a basis for the design of antimalarial therapies targeting metabolic proteins.
A species of malaria plasmodium tends to have rather polymorphic antigens which can serve as immune system targets. Some searches of P. falciparum
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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.
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. 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.
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.
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, Zika virus, dengue and yellow fever).
In a study conducted in 2015, researchers observed a specific interaction between malaria and co-infection with the nematode Nippostrongylus brasiliensis, a pulmonary migrating Parasitic worm, in mice. 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. 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. 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 and in 2023, it has been reported that the bacterium Delftia tsuruhatensis naturally prevents the development of malaria by secreting a molecule called Harmane.
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, therefore utilising this link for management of the vector will contribute in mitigating malaria transmission.
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.
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