malaria malaria malaria is a mosquito-borne infectious disease that affects humans and other animals. malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. in severe cases, it can cause jaundice, seizures, coma, or death. symptoms usually begin ten to fifteen days after being bitten by an infected 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. not to be confused with miliaria. malariamalaria parasite connecting to a red blood cellpronunciation/məˈlɛəriə/ specialtyinfectious diseasesymptomsfever, vomiting, headache, yellow skincomplicationsseizures, coma, organ failure, anemia, cerebral malariausual onset10–15 days post exposurecausesplasmodium spread by mosquitoesdiagnostic methodexamination of the blood, antigen detection testspreventionmosquito nets, insect repellent, mosquito control, medicationsmedicationantimalarial medicationfrequency247 million (2021)deaths619,000 (2021) malaria is caused by single-celled microorganisms of the plasmodium group. it is spread exclusively through bites of infected anopheles mosquitoes. the mosquito bite introduces the parasites from the mosquito's saliva into a person's blood. the parasites travel to the liver where they mature and reproduce. five species of plasmodium can infect and be spread by humans. most deaths are caused by p. falciparum, whereas p. vivax, p. ovale, and p. malariae generally cause a milder form of malaria. the species p. knowlesi rarely causes disease in humans. malaria is typically diagnosed by the microscopic examination of blood using blood films, 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 mosquito nets and insect repellents or with mosquito-control measures such as spraying insecticides 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 2020, there is one vaccine which has been shown to reduce the risk of malaria by about 40% in children in africa. a pre-print study of another vaccine has shown 77% vaccine efficacy. efforts to develop more effective vaccines are ongoing. the recommended treatment for malaria is a combination of antimalarial medications that includes artemisinin. the second medication may be either mefloquine, lumefantrine, or sulfadoxine/pyrimethamine. quinine, along with doxycycline, may be used if artemisinin is not available. it is recommended that in areas where the disease is common, malaria is 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 malarial areas, and resistance to artemisinin has become a problem in some parts of southeast asia. the disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator. this includes much of sub-saharan africa, asia, and latin america. in 2021 there were 247 million cases of malaria worldwide resulting in an estimated 619,000 deaths. approximately 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. 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. signs and complications main symptoms of malaria 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. children tend to have more general symptoms: fever, cough, vomiting, and diarrhea. initial manifestations of the disease—common to all malaria species—are similar to flu-like symptoms, and can resemble other conditions such as sepsis, gastroenteritis, and viral diseases. the presentation may include headache, fever, shivering, joint pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage, and convulsions. 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. 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, seizures, or coma. complications malaria has several serious complications. among these is 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. coinfection of hiv with malaria increases mortality. kidney failure is a feature of blackwater fever, where haemoglobin from lysed red blood cells leaks into the urine. 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 enlarged spleen, enlarged liver or both of these, severe headache, low blood sugar, and haemoglobin in the urine with kidney failure may occur. complications may include spontaneous bleeding, coagulopathy, and shock. malaria in pregnant women is an important cause of stillbirths, infant mortality, miscarriage and low birth weight, particularly in p. falciparum infection, but also with p. vivax. cause malaria is caused by infection with parasites in the genus plasmodium. in humans, malaria is caused by six plasmodium species: p. falciparum, p. malariae, p. ovale curtisi, p. ovale wallikeri, p. vivax and p. knowlesi. among those infected, p. falciparum is the most common species identified (~75%) followed by p. vivax (~20%). although p. falciparum traditionally accounts for the majority of deaths, 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. p. vivax proportionally is more common outside africa. there have been documented human infections with several species of plasmodium from higher apes; however, except for p. knowlesi—a zoonotic species that causes malaria in macaques—these are mostly of limited public health importance. the life cycle of malaria parasites. sporozoites are introduced by a mosquito bite. they migrate to the liver, where they multiply into thousands of merozoites. the merozoites infect red blood cells and replicate, infecting more and more red blood cells. some parasites form gametocytes, which are taken up by a mosquito, continuing the life cycle. parasites are typically introduced by the bite of an infected anopheles mosquito. what these inoculated parasites, called "sporozoites", do in the skin and lymphatics, exactly, has yet to be accurately determined. however, a percentage of sporozoites follow the bloodstream to the liver, where they invade hepatocytes. 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 this invasive form of 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. 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. however, most of the p. vivax replicating merozoite biomass is now (since 2021) known to be hidden in the spleen and bone marrow (perhaps elsewhere too), thereby supporting the astute, long-standing (since 2011) but previously ignored theory that non-circulating merozoites are the source many p. vivax malarial recurrences (see “recurrent malaria” section below). over rounds of this red blood cell infection cycle in the bloodstream and elsewhere, 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. 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. 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. malaria parasites can also be transmitted by blood transfusions, although this is rare. recurrent malaria symptoms of malaria can recur after varying symptom-free periods. depending upon the cause, recurrence can be classified as recrudescence, relapse, or reinfection. recrudescence is when symptoms return after a symptom-free period and the origin is parasites that survived in the blood as a result of inadequate or ineffective treatment. relapse is when symptoms reappear after the parasites have been eliminated from the blood and the recurrence source is activated parasites which had persisted as dormant hypnozoites in liver cells. relapse commonly occurs after 8–24 weeks and is often seen in p. vivax and p. ovale infections. however, relapse-like p. vivax recurrences are probably being over-attributed to hypnozoite activation. some of them might have an extra-vascular or sequestered merozoite origin, making those recurrences recrudescences, not relapses. newly recognised, non-hypnozoite, possible contributing sources to recurrent peripheral p. vivax parasitemia are erythrocytic forms in the bone marrow and spleen. p. vivax malaria cases in temperate areas often involve overwintering by hypnozoites, with relapses beginning the year after the mosquito bite. reinfection means that the parasites responsible for the past infection were eliminated from the body but a new parasite(s) was introduced. reinfection cannot readily be distinguished from relapse and recrudescence, although recurrence of infection within two weeks of treatment for the initial malarial manifestations is typically attributed to treatment failure. but doing this is not necessarily correct. people may develop some immunity when exposed to frequent infections. pathophysiology further information: plasmodium falciparum § pathogenesis micrograph of a placenta from a stillbirth due to maternal malaria. h&e stain. red blood cells are anuclear; blue/black staining in bright red structures (red blood cells) indicate foreign nuclei from the parasites. electron micrograph of a plasmodium falciparum-infected red blood cell (center), illustrating adhesion protein "knobs" 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