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Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes
symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
that typically include
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
, tiredness,
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis ...
, and
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result of ...
s. In severe cases, it can cause
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
,
seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
,
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
, or
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
. Symptoms usually begin ten to fifteen days after being bitten by an infected
mosquito Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning "gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "litt ...
. 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. Malaria is caused by single-celled microorganisms of the ''
Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a verteb ...
'' group. It is spread exclusively through bites of infected ''
Anopheles ''Anopheles'' () is a genus of mosquito first described and named by J. W. Meigen in 1818. About 460 species are recognised; while over 100 can transmit human malaria, only 30–40 commonly transmit parasites of the genus ''Plasmodium'', which c ...
'' mosquitoes. The mosquito bite introduces the parasites from the mosquito's
saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
into a person's blood. The parasites travel to the
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
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 film A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in th ...
s, or with antigen-based
rapid diagnostic test A rapid diagnostic test (RDT) is a medical diagnostic test that is quick and easy to perform. RDTs are suitable for preliminary or emergency medical screening and for use in medical facilities with limited resources. They also allow point-of-care ...
s. Methods that use the
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
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 net A mosquito net is a type of meshed curtain that is circumferentially draped over a bed or a sleeping area, to offer the sleeper barrier protection against bites and stings from mosquitos, flies, and other pest insects, and thus against the d ...
s and
insect repellent An insect repellent (also commonly called "bug spray") is a substance applied to skin, clothing, or other surfaces to discourage insects (and arthropods in general) from landing or climbing on that surface. Insect repellents help prevent and cont ...
s or with mosquito-control measures such as spraying
insecticide Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to ...
s and draining
standing water Water stagnation occurs when water stops flowing. Stagnant water can be a major environmental hazard. Dangers Malaria and dengue are among the main dangers of stagnant water, which can become a breeding ground for the mosquitoes that transmi ...
. Several medications are available to prevent malaria for travellers in areas where the disease is common. Occasional doses of the combination medication
sulfadoxine/pyrimethamine Sulfadoxine/pyrimethamine, sold under the brand name Fansidar, is a combination medication used to treat malaria. It contains sulfadoxine (a sulfonamide) and pyrimethamine (an antiprotozoal). For the treatment of malaria it is typically used alo ...
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 A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
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, but this study has not yet passed peer review. Efforts to develop more effective vaccines are ongoing. The recommended treatment for malaria is a
combination In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are t ...
of
antimalarial medication Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...
s that includes
artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to ''Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her di ...
. The second medication may be either
mefloquine Mefloquine, sold under the brand name Lariam among others, is a medication used to prevent or treat malaria. When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure. It ...
,
lumefantrine Lumefantrine (or benflumetol) is an antimalarial drug. It is only used in combination with artemether. The term "co-artemether" is sometimes used to describe this combination. Lumefantrine has a much longer half-life compared to artemether, and ...
, or sulfadoxine/pyrimethamine.
Quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg c ...
, along with
doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
, 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 Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...
. Resistance among the parasites has developed to several antimalarial medications; for example,
chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...
-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 The tropics are the regions of Earth surrounding the Equator. They are defined in latitude by the Tropic of Cancer in the Northern Hemisphere at N and the Tropic of Capricorn in the Southern Hemisphere at S. The tropics are also referred to ...
and
subtropical The subtropical zones or subtropics are geographical and climate zones to the north and south of the tropics. Geographically part of the temperate zones of both hemispheres, they cover the middle latitudes from to approximately 35° north and ...
regions that exist in a broad band around the
equator The equator is a circle of latitude, about in circumference, that divides Earth into the Northern and Southern hemispheres. It is an imaginary line located at 0 degrees latitude, halfway between the North and South poles. The term can al ...
. This includes much of
sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the African c ...
,
Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
, and
Latin America Latin America or * french: Amérique Latine, link=no * ht, Amerik Latin, link=no * pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived f ...
. In 2020 there were 241 million cases of malaria worldwide resulting in an estimated 627,000 deaths. Approximately 95% of the cases and deaths occurred in sub-Saharan Africa. Rates of disease have decreased from 2010 to 2014 but increased from 2015 to 2020. 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

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 Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another like ...
. 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 Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss ...
, and can resemble other conditions such as
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
,
gastroenteritis Gastroenteritis, also known as infectious diarrhea and gastro, is an inflammation of the gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydrat ...
, and
viral disease A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Structural Characteristics Basic structural characteristics, ...
s. The presentation may include
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result of ...
,
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
,
shivering Shivering (also called shuddering) is a bodily function in response to cold and extreme fear in warm-blooded animals. When the core body temperature drops, the shivering reflex is triggered to maintain homeostasis. Skeletal muscles begin to s ...
,
joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...
,
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis ...
,
hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonl ...
,
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
, hemoglobin in the urine, retinal damage, and
convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
s. The classic symptom of malaria is
paroxysm Paroxysmal attacks or paroxysms (from Greek παροξυσμός) are a sudden recurrence or intensification of symptoms, such as a spasm or seizure. These short, frequent symptoms can be observed in various clinical conditions. They are usually ...
—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 Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal c ...
symptoms, including
abnormal posturing Abnormal posturing is an involuntary flexion or extension of the arms and legs, indicating severe brain injury. It occurs when one set of muscles becomes incapacitated while the opposing set is not, and an external stimulus such as pain caus ...
,
nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...
,
conjugate gaze palsy Conjugate gaze palsies are neurological disorders affecting the ability to move both eyes in the same direction. These palsies can affect gaze in a horizontal, upward, or downward direction. These entities overlap with ophthalmoparesis and ophtha ...
(failure of the eyes to turn together in the same direction),
opisthotonus Opisthotonus or opisthotonos (from grc, ὄπισθεν, translit=opisthen, lit=behind and grc, τόνος, translit=tonos, lit=tension, label=none) is a state of severe hyperextension and spasticity in which an individual's head, neck and spinal ...
,
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s, or
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
.


Complications

Malaria has several serious complications. Among these is the development of
respiratory distress Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing dis ...
, 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 Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...
, noncardiogenic
pulmonary oedema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due to ...
, concomitant
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...
, and severe
anaemia Anemia or anaemia ( British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...
. Although rare in young children with severe malaria,
acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin colo ...
occurs in 5–25% of adults and up to 29% of pregnant women.
Coinfection Coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with hepatitis ...
of
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
with malaria increases mortality.
Kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
is a feature of
blackwater fever Blackwater fever is a complication of malaria infection in which red blood cells burst in the bloodstream (hemolysis), releasing hemoglobin directly into the blood vessels and into the urine, frequently leading to kidney failure. The disease w ...
, 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 Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
. It is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever. An
enlarged spleen Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulatin ...
,
enlarged liver Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdomi ...
or both of these, severe headache,
low blood sugar Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
, and haemoglobin in the urine with
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
may occur. Complications may include spontaneous bleeding,
coagulopathy Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding (bleeding diathesis), which may occur spo ...
, and shock. Malaria in pregnant women is an important cause of
stillbirth Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...
s,
infant mortality Infant mortality is the death of young children under the age of 1. This death toll is measured by the infant mortality rate (IMR), which is the probability of deaths of children under one year of age per 1000 live births. The under-five morta ...
,
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
and
low birth weight Low birth weight (LBW) is defined by the World Health Organization as a birth weight of an infant of or less, regardless of gestational age. Infants born with LBW have added health risks which require close management, often in a neonatal intensi ...
, particularly in ''P. falciparum'' infection, but also with ''P. vivax''.


Cause

Malaria is caused by infection with parasites in the genus ''
Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a verteb ...
''. 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 A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a huma ...
species that causes malaria in
macaques The macaques () constitute a genus (''Macaca'') of gregarious Old World monkeys of the subfamily Cercopithecinae. The 23 species of macaques inhabit ranges throughout Asia, North Africa, and (in one instance) Gibraltar. Macaques are principall ...
—these are mostly of limited public health importance. Parasites are typically introduced by the bite of an infected ''
Anopheles ''Anopheles'' () is a genus of mosquito first described and named by J. W. Meigen in 1818. About 460 species are recognised; while over 100 can transmit human malaria, only 30–40 commonly transmit parasites of the genus ''Plasmodium'', which c ...
'' mosquito. What these inoculated parasites, called "
sporozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
s", do in the skin and lymphatics, exactly, has yet to be accurately determined. However, a percentage of sporozoites follow the bloodstream to the
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
, where they invade
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s. 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 "
merozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
s" into the bloodstream. In the blood, the merozoites rapidly invade individual
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s, 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 "
gametocyte A gametocyte is a eukaryotic germ cell that divides by mitosis into other gametocytes or by meiosis into gametids during gametogenesis. Male gametocytes are called ''spermatocytes'', and female gametocytes are called ''oocytes''. Development ...
s". 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 gland The salivary glands in mammals are exocrine glands that produce saliva through a system of ducts. Humans have three paired major salivary glands (parotid, submandibular, and sublingual), as well as hundreds of minor salivary glands. Salivary glan ...
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 The litre (international spelling) or liter (American English spelling) (SI symbols L and l, other symbol used: ℓ) is a metric unit of volume. It is equal to 1 cubic decimetre (dm3), 1000 cubic centimetres (cm3) or 0.001 cubic metre (m3). ...
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 Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...
. In the brain, they contribute to
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
. 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 transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
s, 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 Recrudescence is the revival of material or behavior that had previously been stabilized, settled, or diminished. In medicine, it is usually defined as the recurrence of symptoms after a period of remission or quiescence, in which sense it can s ...
,
relapse In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or r ...
, 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 In geography, the temperate climates of Earth occur in the middle latitudes (23.5° to 66.5° N/S of Equator), which span between the tropics and the polar regions of Earth. These zones generally have wider temperature ranges throughout t ...
areas often involve
overwintering Overwintering is the process by which some organisms pass through or wait out the winter season, or pass through that period of the year when "winter" conditions (cold or sub-zero temperatures, ice, snow, limited food supplies) make normal activ ...
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 Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity desc ...
when exposed to frequent infections.


Pathophysiology

Malaria infection develops via two phases: one that involves the
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
(exoerythrocytic phase), and one that involves red blood cells, or
erythrocyte Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s (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. 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. Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells. 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 The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinter ...
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. The blockage of the microvasculature causes symptoms such as those in placental malaria. Sequestered red blood cells can breach the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where neu ...
and cause cerebral malaria.


Genetic resistance

According to a 2005 review, due to the high levels of
mortality Mortality is the state of being mortal, or susceptible to death; the opposite of immortality. Mortality may also refer to: * Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...
and
morbidity A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
caused by malaria—especially the ''P. falciparum'' species—it has placed the greatest
selective pressure Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...
on the
human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual Mitochondrial DNA, mitochondria. These are usually treated s ...
in recent history. Several genetic factors provide some resistance to it including
sickle cell trait Sickle cell trait describes a condition in which a person has one abnormal allele of the hemoglobin beta gene (is heterozygous), but does not display the severe symptoms of sickle cell disease that occur in a person who has two copies of that all ...
,
thalassaemia Thalassemias are inherited blood disorders characterized by decreased hemoglobin production. Symptoms depend on the type and can vary from none to severe. Often there is mild to severe anemia (low red blood cells or hemoglobin). Anemia can result ...
traits,
glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
, and the absence of
Duffy antigen Duffy antigen/chemokine receptor (DARC), also known as Fy glycoprotein (FY) or CD234 (Cluster of Differentiation 234), is a protein that in humans is encoded by the ''ACKR1'' gene. The Duffy antigen is located on the surface of red blood cells, ...
s on red blood cells. The impact 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 A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
; 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 Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. M ...
(with two copies of the abnormal haemoglobin beta
allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...
) 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.


Liver dysfunction

Liver dysfunction as a result of malaria is uncommon and usually only occurs in those with another liver condition such as
viral hepatitis Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. The most common causes of viral hepatitis are the five unrelated hepatotropic v ...
or
chronic liver disease Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease ...
. The syndrome is sometimes called ''malarial hepatitis''. 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.


Diagnosis

Due to the non-specific nature of malaria symptoms, diagnosis is typically suspected based on symptoms and travel history, then confirmed with a parasitological test. In areas where malaria is common, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(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. Malaria should similarly be suspected in children with signs of
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
: pale palms or a laboratory test showing
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
levels below 8
gram The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram. Originally defined as of 1795 as "the absolute weight of a volume of pure water equal to th ...
s per
deciliter The litre (international spelling) or liter (American English spelling) (SI symbols L and l, other symbol used: ℓ) is a metric unit of volume. It is equal to 1 cubic decimetre (dm3), 1000 cubic centimetres (cm3) or 0.001 cubic metre (m3). ...
of blood. In areas 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. Malaria is usually confirmed by the microscopic examination of
blood film A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in th ...
s or by
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
-based rapid diagnostic tests (RDT). Microscopy – i.e. examining
Giemsa Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups of ...
-stained blood with a
light microscope The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microsc ...
– is the
gold standard A gold standard is a monetary system in which the standard economic unit of account is based on a fixed quantity of gold. The gold standard was the basis for the international monetary system from the 1870s to the early 1920s, and from the la ...
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 The litre (international spelling) or liter (American English spelling) (SI symbols L and l, other symbol used: ℓ) is a metric unit of volume. It is equal to 1 cubic decimetre (dm3), 1000 cubic centimetres (cm3) or 0.001 cubic metre (m3). ...
of blood, which is around the lower range of symptomatic infection. Microscopic diagnosis is relatively resource intensive, requiring trained personnel, specific equipment, electricity, and a consistent supply of microscopy slides and stains. In places where microscopy is unavailable, malaria is diagnosed with RDTs,
rapid antigen test A rapid antigen test (RAT), sometimes called a rapid antigen detection test (RADT), antigen rapid test (ART), or loosely just a rapid test, is a rapid diagnostic test suitable for point-of-care testing that directly detects the presence or absen ...
s that detect parasite proteins in a
fingerstick In medicine, some blood tests are conducted on capillary blood obtained by fingerstick (or fingerprick) (or, for neonates, by an analogous heelprick). The site, free of surface arterial flow, where the blood is to be collected is sterilized with ...
blood sample. A variety of RDTs are commercially available, targeting the parasite proteins histidine rich protein 2 (HRP2, detects ''P. falciparum'' only),
lactate dehydrogenase Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one ...
, or
aldolase Fructose-bisphosphate aldolase (), often just aldolase, is an enzyme catalyzing a reversible reaction that splits the aldol, fructose 1,6-bisphosphate, into the triose phosphates dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate ( ...
. 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. 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. 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.


Classification

Malaria is classified into either "severe" or "uncomplicated" by the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO). It is deemed severe when ''any'' of the following criteria are present, otherwise it is considered uncomplicated. * Decreased consciousness * Significant weakness such that the person is unable to walk * Inability to feed * Two or more
convulsions A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
*
Low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...
(less than 70 
mmHg A millimetre of mercury is a manometric unit of pressure, formerly defined as the extra pressure generated by a column of mercury one millimetre high, and currently defined as exactly pascals. It is denoted mmHg or mm Hg. Although not an ...
in adults and 50 mmHg in children) * Breathing problems *
Circulatory shock Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thir ...
*
Kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
or
haemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
in the urine * Bleeding problems, or hemoglobin less than 50 g/L (5 g/dL) *
Pulmonary oedema Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due to ...
*
Blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
less than 2.2 mmol/L (40 mg/dL) *
Acidosis Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describes ...
or lactate levels of greater than 5 mmol/L * A parasite level in the blood of greater than 100,000 per
microlitre The litre (international spelling) or liter (American English spelling) (SI symbols L and l, other symbol used: ℓ) is a metric unit of volume. It is equal to 1 cubic decimetre (dm3), 1000 cubic centimetres (cm3) or 0.001 cubic metre (m3). ...
(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 The Glasgow Coma Scale (GCS) is a clinical scale used to reliably measure a person's level of consciousness after a brain injury. The GCS assesses a person based on their ability to perform eye movements, speak, and move their body. These thre ...
less than 11, or a
Blantyre coma scale The Blantyre coma scale is a modification of the Pediatric Glasgow Coma Scale, designed to assess malarial coma in children. It was designed by Terrie Taylor and Malcolm Molyneux in 1987, and named for the Malawian city of Blantyre Blantyre ...
less than 3), or with a coma that lasts longer than 30 minutes after a seizure.


Prevention

Methods used to prevent malaria include medications, mosquito elimination and the prevention of bites. As of 2020, there is one vaccine for malaria (known as
RTS,S RTS,S/AS01 (trade name Mosquirix) is a recombinant protein-based malaria vaccine. In October 2021, the vaccine was endorsed by the World Health Organization (WHO) for "broad use" in children, making it the first malaria vaccine candidate, and ...
) which is licensed for use. The presence of malaria in an area requires a combination of high human population density, high ''
Anopheles ''Anopheles'' () is a genus of mosquito first described and named by J. W. Meigen in 1818. About 460 species are recognised; while over 100 can transmit human malaria, only 30–40 commonly transmit parasites of the genus ''Plasmodium'', which c ...
'' 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. 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 province The provincial level administrative divisions () are the highest-level administrative divisions of China. There are 34 such divisions claimed by the People's Republic of China, classified as 23 provinces (), five autonomous regions of China, au ...
s—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 confirms that China has eliminated malaria. In areas where malaria is common, children under five years old often have
anaemia Anemia or anaemia ( British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...
, 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.


Mosquito control

Vector control Vector control is any method to limit or eradicate the mammals, birds, insects or other arthropods (here collectively called " vectors") which transmit disease pathogens. The most frequent type of vector control is mosquito control using a vari ...
refers to methods used to decrease malaria by reducing the levels of transmission by mosquitoes. For individual protection, the most effective
insect repellent An insect repellent (also commonly called "bug spray") is a substance applied to skin, clothing, or other surfaces to discourage insects (and arthropods in general) from landing or climbing on that surface. Insect repellents help prevent and cont ...
s are based on
DEET ''N'',''N''-Diethyl-''meta''-toluamide, also called DEET () or diethyltoluamide, is the most common active ingredient in insect repellents. It is a slightly yellow oil intended to be applied to the skin or to clothing and provides protection a ...
or picaridin. However, there is insufficient evidence that mosquito repellents can prevent malaria infection. Insecticide-treated nets (ITNs) and
indoor residual spraying Indoor residual spraying or IRS is the process of spraying the inside of dwellings with an insecticide to kill mosquitoes that spread malaria. A dilute solution of insecticide is sprayed on the inside walls of certain types of dwellings—those w ...
(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. 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. Modifications to people's houses to prevent mosquito exposure may be an important long term prevention measure.


Insecticide-treated nets

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. Between 2000 and 2008, the use of ITNs saved the lives of an estimated 250,000 infants in Sub-Saharan Africa. About 13% of households in Sub-Saharan countries owned ITNs in 2007 and 31% of African households were estimated to own at least one ITN in 2008. 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 and to 68% African children using mosquito nets in 2015. Most nets are impregnated with
pyrethroid A pyrethroid is an organic compound similar to the natural pyrethrins, which are produced by the flowers of pyrethrums (''Chrysanthemum cinerariaefolium'' and '' C. coccineum''). Pyrethroids are used as commercial and household insecticides. In ...
s, a class of insecticides with low
toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a su ...
. They are most effective when used from dusk to dawn. 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. ITNs are beneficial towards pregnancy outcomes in malaria-endemic regions in Africa but more data is needed in Asia and Latin America. 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 impact on mosquito mortality was not sustained after twenty washes in experimental trials.


Indoor residual spraying

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. As of 2006, the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
recommends 12 insecticides in IRS operations, including
DDT Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. ...
and the pyrethroids cyfluthrin and
deltamethrin Deltamethrin is a pyrethroid ester insecticide. Deltamethrin plays a key role in controlling malaria vectors, and is used in the manufacture of long-lasting insecticidal mosquito nets; however, resistance of mosquitos and bed bugs to deltamethrin ...
. This public health use of small amounts of DDT is permitted under the
Stockholm Convention Stockholm Convention on Persistent Organic Pollutants is an international environmental treaty, signed on 22 May 2001 in Stockholm and effective from 17 May 2004, that aims to eliminate or restrict the production and use of persistent organic ...
, which prohibits its agricultural use. One problem with all forms of IRS is
insecticide resistance Pesticide resistance describes the decreased susceptibility of a pest population to a pesticide that was previously effective at controlling the pest. Pest species evolve pesticide resistance via natural selection: the most resistant specimens su ...
. 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. Communities using insecticide treated nets, in addition to indoor residual spraying with 'non-pyrethroid-like' insecticides found associated reductions in malaria. 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.


Housing modifications

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
pyrethroid A pyrethroid is an organic compound similar to the natural pyrethrins, which are produced by the flowers of pyrethrums (''Chrysanthemum cinerariaefolium'' and '' C. coccineum''). Pyrethroids are used as commercial and household insecticides. In ...
s. 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.


Other mosquito control methods

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. Electronic mosquito repellent devices, which make very high-frequency sounds that are supposed to keep female mosquitoes away, have no supporting evidence of effectiveness. There is a low certainty evidence that fogging may have an effect on malaria transmission. Larviciding by hand delivery of chemical or microbial insecticides into water bodies containing low larval distribution may reduce malarial transmission. There is insufficient evidence to determine whether larvivorous fish can decrease mosquito density and transmission in the area.


Medications

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 Mefloquine, sold under the brand name Lariam among others, is a medication used to prevent or treat malaria. When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure. It ...
,
doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
, or the combination of
atovaquone/proguanil Atovaquone/proguanil, sold under the brand name Malarone among others, is a fixed-dose combination medication used to treat and prevent malaria, including chloroquine-resistant malaria. It contains atovaquone and proguanil. It is not recommended ...
(''Malarone'')—are frequently used for prevention. Doxycycline and the atovaquone/proguanil are better tolerated while mefloquine is taken once a week. Areas of the world with
chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...
-sensitive malaria are uncommon. 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. Other factors such as drug administration plus other protective measures such as mosiquito 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. 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 In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
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 Anemia or anaemia ( British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...
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 sulfadoxine-pyrimethamine for three or more doses as intermittent preventive therapy is superior than two doses for HIV-positive women living in malaria-endemic areas. Prompt treatment of confirmed cases with artemisinin-based combination therapies (ACTs) may also reduce transmission.


Others

Community participation and
health education Health education is a profession of educating people about health. Areas within this profession encompass environmental health, physical health, social health, emotional health, intellectual health, and spiritual health, as well as sexual and r ...
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. 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.
Intermittent preventive therapy Intermittent preventive therapy or intermittent preventive treatment (IPT) is a public health intervention aimed at treating and preventing malaria episodes in infants (IPTi), children (IPTc), schoolchildren (IPTsc) and pregnant women (IPTp). The in ...
is another intervention that has been used successfully to control malaria in pregnant women and infants, and in preschool children where transmission is seasonal.


Treatment

Malaria is treated with
antimalarial medication Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...
s; the ones used depends on the type and severity of the disease. While medications against fever are commonly used, their effects on outcomes are not clear. 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.


Uncomplicated malaria

Simple or uncomplicated malaria may be treated with oral medications. Artemisinin drugs are effective and safe in treating uncomplicated malaria. Artemisinin in combination with other antimalarials (known as artemisinin-combination therapy, or ACT) is about 90% effective when used to treat uncomplicated malaria. The most effective treatment for ''P. falciparum'' infection is the use of ACT, which decreases resistance to any single drug component. 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. Another recommended combination is
dihydroartemisinin Dihydroartemisinin (also known as dihydroqinghaosu, artenimol or DHA) is a drug used to treat malaria. Dihydroartemisinin is the active metabolite of all artemisinin compounds (artemisinin, artesunate, artemether, etc.) and is also available as ...
and
piperaquine Piperaquine is an antiparasitic drug used in combination with dihydroartemisinin to treat malaria. Piperaquine was developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement f ...
. Artemisinin-naphthoquine combination therapy showed promising results in treating falciparum malaria. However, more research is needed to establish its efficacy as a reliable treatment. Artesunate plus mefloquine performs better than mefloquine alone in treating uncomplicated falciparum malaria in low transmission settings. Atovaquone-proguanil is effective against uncomplicated falciparum with a possible failure rate of 5% to 10%; the addition of artesunate may reduce failure rate. Azithromycin monotherapy or combination therapy has not shown effectiveness in treating plasmodium or vivax malaria. Amodiaquine plus sulfadoxine-pyrimethamine may achieve less treatment failures when compared to sulfadoxine-pyrimethamine alone in uncomplicated falciparum malaria. There is insufficient data on chlorproguanil-dapsone in treating uncomplicated falciparum malaria. The addition of primaquine with artemisinin-based combination therapy for falciparum malaria reduces its transmission at day 3-4 and day 8 of infection. 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. Infection with ''P. vivax'', ''P. ovale'' or ''P. malariae'' usually does not require hospitalisation. Treatment of ''P. vivax'' malaria requires both elimination of blood stages (using chloroquine or artemisinin-based combination therapy) and clearance of liver forms with an 8-aminoquinoline agent such as
primaquine Primaquine is a medication used to treat and prevent malaria and to treat ''Pneumocystis'' pneumonia. Specifically it is used for malaria due to ''Plasmodium vivax'' and '' Plasmodium ovale'' along with other medications and for prevention if oth ...
or tafenoquine. The view that 8-aminoquinoline drugs kill parasites in the liver is the conventional one. However, there are reasons to believe that primaquine might, to a currently unknown extent, also inactivate non-circulating, extra-hepatic merozoites (clarity in this regard is expected to be forthcoming soon). To treat malaria during pregnancy, the
WHO Who or WHO may refer to: * Who (pronoun), an interrogative or relative pronoun * Who?, one of the Five Ws in journalism * World Health Organization Arts and entertainment Fictional characters * Who, a creature in the Dr. Seuss book ''Horton Hear ...
recommends the use of quinine plus
clindamycin Clindamycin is an antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (middle ear infect ...
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.


Severe and complicated malaria

Cases of severe and complicated malaria are almost always caused by infection with ''P. falciparum''. The other species usually cause only febrile disease. Severe and complicated malaria cases are medical emergencies since mortality rates are high (10% to 50%). Recommended treatment for severe malaria is the
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
use of antimalarial drugs. For severe malaria,
parenteral A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...
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 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 Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
. Artemisinin derivatives have the same or better efficacy than quinolones in preventing deaths in severe or complicated malaria. Quinine
loading dose In pharmacokinetics, a loading dose is an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose. A loading dose is most useful for drugs that are eliminated fro ...
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. 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
convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
s but possibly more deaths. There is no evidence that steroids would bring treatment benefits for cerebral malaria. Managing Cerebral Malaria Cerebral malaria usually makes a patient comatose, if the cause of the coma is in doubt, test 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. To manage the cerebral malaria when confirmed the following can be done: * Patients 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. 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 The hematocrit () (Ht or HCT), also known by several other names, is the volume percentage (vol%) of red blood cells (RBCs) in blood, measured as part of a blood test. The measurement depends on the number and size of red blood cells. It is no ...
in one month. There is insufficient evidence that iron chelating agents such as deferoxamine and deferiprone improve outcomes of those with malaria falciparum infection.


Resistance

Drug resistance Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...
poses a growing problem in 21st-century malaria treatment. In the 2000s (decade), malaria with partial resistance to artemisins emerged in Southeast Asia. Resistance is now common against all classes of antimalarial drugs apart from
artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to ''Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her di ...
s. Treatment of resistant strains became increasingly dependent on this class of drugs. The cost of artemisinins limits their use in the developing world. Malaria strains found on the Cambodia–Thailand border are resistant to combination therapies that include artemisinins, and may, therefore, be untreatable. 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. Resistance to artemisinin has been detected in Cambodia, Myanmar, Thailand, and Vietnam, and there has been emerging resistance in Laos.Briggs, Helen (30 July 2014
Call for 'radical action' on drug-resistant malaria
BBC News, health, Retrieved 30 July 2013
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 Laos (, ''Lāo'' )), officially the Lao People's Democratic Republic ( Lao: ສາທາລະນະລັດ ປະຊາທິປະໄຕ ປະຊາຊົນລາວ, French: République démocratique populaire lao), is a socialist ...
,
Thailand Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is b ...
and
Vietnam Vietnam or Viet Nam ( vi, Việt Nam, ), officially the Socialist Republic of Vietnam,., group="n" is a country in Southeast Asia, at the eastern edge of mainland Southeast Asia, with an area of and population of 96 million, making it ...
(with up to 80 percent of malaria parasites resistant in some regions). 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.


Prognosis

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,
fatality rate In epidemiology, case fatality rate (CFR) – or sometimes more accurately case-fatality risk – is the proportion of people diagnosed with a certain disease, who end up dying of it. Unlike a disease's mortality rate, the CFR does not take int ...
s 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 ''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is furt ...
'' bacteria and the
Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...
. 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 Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
. Malaria prophylaxis was shown to improve cognitive function and school performance in
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s when compared to
placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can aff ...
groups.


Epidemiology

The WHO estimates that in 2019 there were 229 million new cases of malaria resulting in 409,000 deaths. Children under 5 years old are the most affected, accounting for 67% of malaria deaths worldwide in 2019. About 125 million pregnant women are at risk of infection each year; in
Sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the African c ...
, maternal malaria is associated with up to 200,000 estimated infant deaths yearly. There are about 10,000 malaria cases per year in Western Europe, and 1300–1500 in the United States. The United States eradicated malaria as a major public health concern in 1951, though small outbreaks persist. About 900 people died from the disease in Europe between 1993 and 2003. 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% from a 2000 estimate of 985,000, largely due to the widespread use of insecticide-treated nets and artemisinin-based combination therapies. In 2012, there were 207 million cases of malaria. That year, the disease is estimated to have killed between 473,000 and 789,000 people, many of whom were children in Africa. Efforts at decreasing the disease in Africa since 2000 have been partially effective, with rates of the disease dropping by an estimated forty percent on the continent. Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; in Sub-Saharan Africa, 85–90% of malaria fatalities occur. An estimate for 2009 reported that countries with the highest death rate per 100,000 of population were
Ivory Coast Ivory Coast, also known as Côte d'Ivoire, officially the Republic of Côte d'Ivoire, is a country on the southern coast of West Africa. Its capital is Yamoussoukro, in the centre of the country, while its largest city and economic centre is ...
(86.15),
Angola , national_anthem = " Angola Avante"() , image_map = , map_caption = , capital = Luanda , religion = , religion_year = 2020 , religion_ref = , coordina ...
(56.93) and
Burkina Faso Burkina Faso (, ; , ff, 𞤄𞤵𞤪𞤳𞤭𞤲𞤢 𞤊𞤢𞤧𞤮, italic=no) is a landlocked country in West Africa with an area of , bordered by Mali to the northwest, Niger to the northeast, Benin to the southeast, Togo and Ghana to th ...
(50.66). A 2010 estimate indicated the deadliest countries per population were Burkina Faso,
Mozambique Mozambique (), officially the Republic of Mozambique ( pt, Moçambique or , ; ny, Mozambiki; sw, Msumbiji; ts, Muzambhiki), is a country located in southeastern Africa bordered by the Indian Ocean to the east, Tanzania to the north, Malawi ...
and
Mali Mali (; ), officially the Republic of Mali,, , ff, 𞤈𞤫𞤲𞥆𞤣𞤢𞥄𞤲𞤣𞤭 𞤃𞤢𞥄𞤤𞤭, Renndaandi Maali, italics=no, ar, جمهورية مالي, Jumhūriyyāt Mālī is a landlocked country in West Africa. 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 Disease burden is the impact of a health problem as measured by financial cost, mortality, morbidity, or other indicators. It is often quantified in terms of quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Bot ...
. This effort led to the publication of a map of ''P. falciparum'' endemicity in 2010 and an update in 2019. As of 2010, about 100 countries have endemic malaria. Every year, 125 million international travellers visit these countries, and more than 30,000 contract the disease. 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 The Greater Mekong Subregion, (GMS) or just Greater Mekong, is a trans-national region of the Mekong River basin in Southeast Asia. The region is home to more than 300 million people. It came into being with the launch of a development program i ...
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.


Climate change

Climate change is likely to affect malaria transmission, but the degree of effect and the areas affected is uncertain. Greater rainfall in certain areas of India, and following an
El Niño El Niño (; ; ) is the warm phase of the El Niño–Southern Oscillation (ENSO) and is associated with a band of warm ocean water that develops in the central and east-central equatorial Pacific (approximately between the International Date Li ...
event is associated with increased mosquito numbers. 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.


History

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 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. References to the unique periodic fevers of malaria are found throughout history. Hippocrates described periodic fevers, labelling them tertian, quartan, subtertian and quotidian. The Roman
Columella Lucius Junius Moderatus Columella (; Arabic: , 4 – ) was a prominent writer on agriculture in the Roman Empire. His ' in twelve volumes has been completely preserved and forms an important source on Roman agriculture, together with the wo ...
associated the disease with insects from swamps. Malaria may have contributed to the decline of the
Roman Empire The Roman Empire ( la, Imperium Romanum ; grc-gre, Βασιλεία τῶν Ῥωμαίων, Basileía tôn Rhōmaíōn) was the post-Roman Republic, Republican period of ancient Rome. As a polity, it included large territorial holdings aro ...
, 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 Sardinia ( ; it, Sardegna, label=Italian language, Italian, Corsican language, Corsican and Tabarchino ; sc, Sardigna , sdc, Sardhigna; french: Sardaigne; sdn, Saldigna; ca, Sardenya, label=Algherese dialect, Algherese and Catalan languag ...
, the
Pontine Marshes 250px, Lake Fogliano, a coastal lagoon in the Pontine Plain The Pontine Marshes (, also ; it, Agro Pontino , formerly also ''Paludi Pontine''; la, Pomptinus Ager by Titus Livius, ''Pomptina Palus'' (singular) and ''Pomptinae Paludes'' (plur ...
, the lower regions of coastal Etruria and the city of
Rome , established_title = Founded , established_date = 753 BC , founder = King Romulus (Romulus and Remus, legendary) , image_map = Map of comune of Rome (metropolitan city of Capital Rome, region Lazio, Italy).svg ...
along the
Tiber The Tiber ( ; it, Tevere ; la, Tiberis) is the third-longest river in Italy and the longest in Central Italy, rising in the Apennine Mountains in Emilia-Romagna and flowing through Tuscany, Umbria, and Lazio, where it is joined by the Ri ...
. 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. The term malaria originates from
Mediaeval In the history of Europe, the Middle Ages or medieval period lasted approximately from the late 5th to the late 15th centuries, similar to the post-classical period of global history. It began with the fall of the Western Roman Empire a ...
it, mala aria—" bad air"; the disease was formerly called ''ague'' or ''marsh fever'' due to its association with swamps and marshland. The term appeared in English at least as early as 1768. Malaria was once common in most of Europe and North America, where it is no longer endemic, though imported cases do occur. Malaria is not referenced in the medical books of the
Mayans The Maya peoples () are an ethnolinguistic group of Indigenous peoples of the Americas, indigenous peoples of Mesoamerica. The ancient Maya civilization was formed by members of this group, and today's Maya are generally descended from people ...
or
Aztecs The Aztecs () were a Mesoamerican culture that flourished in central Mexico in the post-classic period from 1300 to 1521. The Aztec people included different ethnic groups of central Mexico, particularly those groups who spoke the Nahuatl l ...
. 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 ) , image_map = Algeria (centered orthographic projection).svg , map_caption = , image_map2 = , capital = Algiers , coordinates = , largest_city = capital , relig ...
—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 A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the exclu ...
was identified as causing disease. For this and later discoveries, he was awarded the 1907
Nobel Prize for Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accordin ...
. A year later,
Carlos Finlay Carlos Juan Finlay (December 3, 1833 – August 20, 1915) was a Cuban epidemiologist recognized as a pioneer in the research of yellow fever, determining that it was transmitted through mosquitoes '' Aedes aegypti''. Biography Early life and ...
, a Cuban doctor treating people with
yellow fever Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. I ...
in
Havana Havana (; Spanish: ''La Habana'' ) is the capital and largest city of Cuba. The heart of the La Habana Province, Havana is the country's main port and commercial center.
, provided strong evidence that mosquitoes were transmitting disease to and from humans. This work followed earlier suggestions by
Josiah C. Nott Josiah Clark Nott (March 31, 1804March 31, 1873) was an American surgeon and anthropologist. He is known for his studies into the etiology of yellow fever and malaria, including the theory that they originate from germs. Nott, who owned slaves ...
, and work by Sir Patrick Manson, the "father of tropical medicine", on the transmission of
filariasis Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type. These are spread by blood-feeding insects such as black flies and mosquitoes. They belong to the group of diseases called helminthiases. These pa ...
. In April 1894, a Scottish physician,
Sir Ronald Ross Sir Ronald Ross (13 May 1857 – 16 September 1932) was a British medical doctor who received the Nobel Prize for Physiology or Medicine in 1902 for his work on the transmission of malaria, becoming the first British Nobel laureate, and the f ...
, 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 Kolkata (, or , ; also known as Calcutta , the official name until 2001) is the capital of the Indian state of West Bengal, on the eastern bank of the Hooghly River west of the border with Bangladesh. It is the primary business, commerc ...
, 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 The Indian Medical Service (IMS) was a military medical service in British India, which also had some civilian functions. It served during the two World Wars, and remained in existence until the independence of India in 1947. Many of its officer ...
, Ross worked at the newly established
Liverpool School of Tropical Medicine The Liverpool School of Tropical Medicine (LSTM) is a higher education institution with degree awarding powers and registered charity located in Liverpool, United Kingdom. Established in 1898, it was the first institution in the world dedicated ...
and directed malaria-control efforts in
Egypt Egypt ( ar, مصر , ), officially the Arab Republic of Egypt, is a List of transcontinental countries, transcontinental country spanning the North Africa, northeast corner of Africa and Western Asia, southwest corner of Asia via a land bridg ...
,
Panama Panama ( , ; es, link=no, Panamá ), officially the Republic of Panama ( es, República de Panamá), is a transcontinental country spanning the southern part of North America and the northern part of South America. It is bordered by Cost ...
,
Greece Greece,, or , romanized: ', officially the Hellenic Republic, is a country in Southeast Europe. It is situated on the southern tip of the Balkans, and is located at the crossroads of Europe, Asia, and Africa. Greece shares land borders with ...
and
Mauritius Mauritius ( ; french: Maurice, link=no ; mfe, label=Mauritian Creole, Moris ), officially the Republic of Mauritius, is an island nation in the Indian Ocean about off the southeast coast of the African continent, east of Madagascar. It incl ...
. The findings of Finlay and Ross were later confirmed by a medical board headed by
Walter Reed Walter Reed (September 13, 1851 – November 22, 1902) was a U.S. Army physician who in 1901 led the team that confirmed the theory of Cuban doctor Carlos Finlay that yellow fever is transmitted by a particular mosquito species rather than ...
in 1900. Its recommendations were implemented by
William C. Gorgas William Crawford Gorgas KCMG (October 3, 1854 – July 3, 1920) was a United States Army physician and 22nd Surgeon General of the U.S. Army (1914–1918). He is best known for his work in Florida, Havana and at the Panama Canal in abating t ...
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 Accademia dei Lincei (; literally the "Academy of the Lynx-Eyed", but anglicised as the Lincean Academy) is one of the oldest and most prestigious European scientific institutions, located at the Palazzo Corsini on the Via della Lungara in Ro ...
. The first effective treatment for malaria came from the bark of cinchona tree, which contains
quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg c ...
. This tree grows on the slopes of the Andes, mainly in
Peru , image_flag = Flag of Peru.svg , image_coat = Escudo nacional del Perú.svg , other_symbol = Great Seal of the State , other_symbol_type = National seal , national_motto = "Firm and Happy f ...
. 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. 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". 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 Chinese herbology, 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 resistance, 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. Malaria vaccines have been an elusive goal of research. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunising mice with live, radiation-Attenuator (genetics), attenuated sporozoites, which provided significant protection to the mice upon subsequent injection with normal, viable sporozoites. Since the 1970s, there has been a considerable effort to develop similar vaccination strategies for humans. The first vaccine, called
RTS,S RTS,S/AS01 (trade name Mosquirix) is a recombinant protein-based malaria vaccine. In October 2021, the vaccine was endorsed by the World Health Organization (WHO) for "broad use" in children, making it the first malaria vaccine candidate, and ...
, was approved by European regulators in 2015.


Names

Various types of malaria have been called by the names below:


Eradication efforts

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. The use of the pesticide DDT and other means eliminated malaria from the remaining pockets in southern states of the US the 1950s, as part of the National Malaria Eradication Program. Most of Europe, North America, Australia, North Africa and the Caribbean, and parts of South America,
Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
and Southern Africa have also eliminated malaria. 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 1955 the WHO launched the Global Malaria Eradication Program (GMEP), which supported substantial reductions in malaria cases in some countries, including India. However, due to vector and parasite resistance and other factors, the Eradication of infectious diseases, 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. Target 6C of the Millennium Development Goals included reversal of the global increase in malaria incidence by 2015, with specific targets for children under 5 years old. 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. 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 World Health Assembly, the World Health Assembly. As of 2018, they are still functioning. , The Global Fund to Fight AIDS, Tuberculosis and Malaria, 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 The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO) was formed in 2012, "to provide strategic advice and technical input to WHO on all aspects of malaria control and elimination". In November 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. 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. 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 The Greater Mekong Subregion, (GMS) or just Greater Mekong, is a trans-national region of the Mekong River basin in Southeast Asia. The region is home to more than 300 million people. It came into being with the launch of a development program i ...
countries aim for elimination of Plasmodium falciparum, ''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. One of the targets of Sustainable Development Goal 3, Goal 3 of the United Nations, UN's Sustainable Development Goals is to end the malaria epidemic in all countries by 2030. In 2018, WHO announced that Paraguay was free of malaria, after a national malaria eradication effort that began in 1950. As of 2019, the eradication process is ongoing, but it will be difficult to achieve a world free of malaria with the current approaches and tools. Only one malaria vaccine is licensed for use, and it shows relatively low effectiveness, while several other vaccine candidates in clinical trials aim to provide protection for children in endemic areas and reduce the speed of malaria transmission. Approaches 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.


Society and culture


Economic impact

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. Although Tropics, 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. A comparison of average per capita GDP in 1995, adjusted for purchasing power parity, 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 impact of malaria has been estimated to cost Africa US$12 billion every year. The economic impact 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.


Counterfeit and substandard drugs

Sophisticated counterfeit drugs, counterfeits have been found in several Asian countries such as Cambodia, China, Indonesia,
Laos Laos (, ''Lāo'' )), officially the Lao People's Democratic Republic ( Lao: ສາທາລະນະລັດ ປະຊາທິປະໄຕ ປະຊາຊົນລາວ, French: République démocratique populaire lao), is a socialist ...
,
Thailand Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is b ...
, and
Vietnam Vietnam or Viet Nam ( vi, Việt Nam, ), officially the Socialist Republic of Vietnam,., group="n" is a country in Southeast Asia, at the eastern edge of mainland Southeast Asia, with an area of and population of 96 million, making it ...
, and are a major cause of avoidable death in those countries. 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. 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. 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.


War

Throughout history, the contraction of malaria has played a prominent role in the fates of government rulers, nation-states, military personnel, and military actions. In 1910, Nobel Prize in Medicine-winner 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." In British-occupied India the cocktail Gin and tonic#History, gin and tonic may have come about as a way of taking quinine, known for its antimalarial properties. 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".


Research

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.


Vaccine

A vaccine against malaria called RTS,S, RTS,S/AS01 (RTS,S) was approved by European regulators in 2015. 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, tolerance) to ''P. falciparum'' malaria does occur naturally, but only in response to years of repeated infection. 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. The highly polymorphism (biology), 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, Manuel Elkin Patarroyo, SPf66 was tested extensively in areas where the disease was common in the 1990s, but trials showed it to be insufficiently effective. In 2021, researchers from the University of Oxford reported findings from a Phases of clinical research, 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 The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
's Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy.


Medications

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 Endosymbiont, 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. 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. Antimalarial drugs using Organometallic chemistry, synthetic metal-based coordination complex, complexes are attracting research interest. * (+)-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 Phases of clinical research#Phase 1, Phase 1 clinical trial to assess the safety profile in human is planned by the Howard Hughes Medical Institute. * NITD246 and NITD609: Also belonged to the class of spiroindolone and target the ATP4 protein. 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.


New targets

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. In a research conducted in 2019, using experimental analysis with knockout (KO) mutants of ''Plasmodium berguei'' 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 3 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.


Other

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. Genomics is central to malaria research. With the whole genome sequencing, sequencing of ''P. falciparum'', one of its vectors ''Anopheles gambiae'', and the
human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual Mitochondrial DNA, mitochondria. These are usually treated s ...
, 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 organism, 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, zika, dengue and yellow fever). In December 2020, a review article found that malaria-endemic regions had lower reported COVID-19 case fatality rates on average than regions where malaria was not known to be endemic. Additionally, research conducted in 2015 demonstrated that in mice, malaria co-infection with the nematode ''Nippostrongylus brasiliensis'', a pulmonary migrating Parasitic worm, helminth, has dampened the virulence of the ''Plasmodium'' parasite. Researchers demonstrated bottom-up control of malaria infection by the nematode; specifically, nematode infection leads to increased destruction of erythrocytes. It is known that ''Plasmodium'' prefers older host erythrocytes, which are easier for it to infect, so increased destruction, causing subsequent increased erythropoiesis, leads to an overall younger erythrocyte population resulting in a decrease in ''Plasmodium'' population. Interestingly, this disease control is largely independent of host immune control of ''Plasmodium'', and may provide interesting insights for future treatment.


Other animals

While there are no zoonosis, animal reservoirs for the strains of malaria that cause human infections, nearly 200 parasitic ''Plasmodium'' species have been identified that infect Plasmodium species infecting birds, birds, Plasmodium species infecting reptiles, reptiles, and Plasmodium species infecting mammals other than primates, other mammals, and about 30 species naturally infect non-human primates. Some malaria parasites that affect non-human primates (NHP) serve as model organisms for human malarial parasites, such as ''Plasmodium coatneyi, P. coatneyi'' (a model for ''P. falciparum'') and ''Plasmodium cynomolgi, P. cynomolgi'' (''P. vivax''). Diagnostic techniques used to detect parasites in NHP are similar to those employed for humans. Malaria parasites that infect rodents are widely used as models in research, such as ''Plasmodium berghei, P. berghei''. 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 ''Plasmodium relictum, P. relictum'' is known to play a role in limiting the distribution and abundance of endemic birds of Hawaii, 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.


References


Citations


Sources

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Further reading

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External links


WHO site on malaria



PAHO site on malaria
{{good article Malaria, Plasmodium, *Malaria Insect-borne diseases Infectious diseases with eradication efforts Protozoal diseases Tropical diseases Vaccine-preventable diseases Articles containing video clips