Malaria
Malaria is a mosquito-borne infectious disease which is transmitted by the bite of Anopheles mosquitoes. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. The mosquitoes themselves are harmed by malaria, causing reduced lifespans in those infected by it.
Malaria is caused by single-celled eukaryotes of the genus Plasmodium. In mammals, it is spread through bites of infected female Anopheles mosquitoes. The mosquito bite introduces the parasites from the mosquito's saliva into the blood. The parasites initially reproduce and mature in the liver without causing symptoms. After a few days the mature parasites spread into the bloodstream, where they infect and destroy red blood cells, causing the symptoms of infection. Five species of Plasmodium commonly infect humans. The three species associated with more severe cases are P. falciparum, P. vivax, and P. knowlesi. P. ovale and P. malariae generally cause a milder form of malaria. Malaria is typically diagnosed by the microscopic examination of blood using blood films, or with antigen-based rapid diagnostic tests. Methods that use the polymerase chain reaction to detect the parasite's DNA have been developed, but they are not widely used in areas where malaria is common, due to their cost and complexity.
The risk of disease can be reduced by preventing mosquito bites through the use of mosquito nets and insect repellents or with mosquito-control measures such as spraying insecticides and draining standing water. Several prophylactic medications are available to prevent malaria in areas where the disease is common. As of 2023, two malaria vaccines have been endorsed by the World Health Organization. Resistance among the parasites has developed to several antimalarial medications; for example, chloroquine-resistant P. falciparum has spread to most malaria-prone areas, and resistance to artemisinin has become a problem in some parts of Southeast Asia. Because of this, drug treatment for malaria infection should be tailored to best fit the plasmodium species involved and the geographical location where the infection was acquired.
The disease is widespread in the tropical and subtropical regions that exist in a broad band around the equator. This includes much of sub-Saharan Africa, Asia, and Latin America. In 2023, some 263 million cases of malaria worldwide resulted in an estimated 597,000 deaths. Around 95% of the cases and deaths occurred in sub-Saharan Africa. Malaria is commonly associated with poverty and has a significant negative effect on economic development; in Africa, it is estimated to result in economic losses of US$12 billion a year due to increased healthcare costs, lost ability to work, and adverse effects on tourism.
Etymology
The term malaria originates from Medieval, 'bad air', a part of miasma theory; the disease was formerly called ague, paludism or marsh fever due to its association with swamps and marshland. The term appeared in English at least as early as 1768. The scientific study of malaria is called malariology.Signs and symptoms
Symptoms during the early stages of malaria infection are fever, chills, headache, nausea, and vomiting and diarrhea; more serious cases may show enlarged spleen or liver, and mild jaundice. These symptoms can resemble other conditions such as sepsis, gastroenteritis, flu and other viral diseases. Without treatment, symptoms - particularly the fever - can settle into a regular pattern, recurring every two or three days.Symptoms typically begin 10–15 days after the initial mosquito bite, but can occur as late as several months after infection. Travellers taking preventative malaria medications may develop symptoms once they stop taking the drugs.
Severe malaria occurs when the Plasmodium infection causes damage to vital organs such as the kidney, liver, lungs or brain. Symptoms include severe anemia, jaundice, convulsions, confusion, coma, kidney failure and eventually death.. Severe malaria is usually caused by P. falciparum; it should be treated as a medical emergency.
Complications
A unique feature of P falciparum is its ability to generate adhesive proteins on the surface of infected red blood cells. Infected RBCs obstruct capillaries and accumulate in vital organs, interfering with their function. P falciparum infection underlies most severe complications of malaria.Cerebral malaria is a form of severe malaria affecting the brain. Infected RBCs blocking capillaries in the brain trigger an immune reaction, which in turn damages the blood-brain barrier. Individuals with cerebral malaria exhibit neurological symptoms, such as confusion, seizures, or coma. Cerebral malaria, if untreated, can lead to death within forty-eight hours of the first symptoms; survivors may have long-term neurological damage.
Severe anemia is caused by a combination of the destruction of RBCs together with reduced RBC production in the bone marrow; it is a major cause of deaths in children under 5.
Malaria can lead to acute respiratory distress syndrome in up to 25% of cases. It is caused by damage to the capillary endothelium, in turn damaging the alveoli of the lung. Symptoms are extreme shortness of breath and a bluish tinge to the lips indicating lack of oxygen. It is a leading killer adults, with around 40% mortality once symptoms begin.
Coinfection of HIV with malaria increases mortality.
Other complications include an enlarged spleen, enlarged liver or both of these. So-called blackwater fever occurs when haemoglobin from lysed red blood cells leaks into and discolours the urine; this often precedes kidney failure.
Malaria during pregnancy can cause stillbirths, infant mortality, miscarriage, and low birth weight, particularly in P. falciparum infection, but also with P. vivax.
Cause
Malaria is caused by infection with parasites in the genus Plasmodium, which are transmitted between the human hosts by mosquitoes in the genus Anopheles.Life cycle
The plasmodium parasite has a complex life cycle involving human and mosquito hosts, taking a different form at each stage of the cycle.The liver infection causes no symptoms; all symptoms of malaria result from the infection of red blood cells. Symptoms develop once there are more than around 100,000 parasites per milliliter of blood. Many of the symptoms associated with severe malaria are caused by the tendency of P. falciparum to bind to blood vessel walls, resulting in damage to the affected vessels and surrounding tissue. Parasites sequestered in the blood vessels of the lung contribute to respiratory failure. In the brain, they contribute to coma. During pregnancy they accumulate in the intervillous space and hinder the function of the placenta, contributing to low birthweight and preterm labor, and increasing the risk of abortion and stillbirth. The destruction of red blood cells during infection often results in anemia, exacerbated by reduced production of new red blood cells during infection.
Only female mosquitoes feed on blood; male mosquitoes feed on plant nectar and do not transmit the disease. Females of the mosquito genus Anopheles prefer to feed at night. They usually start searching for a meal at dusk, and continue through the night until they succeed. However, they may be adapting to the extensive use of bed nets and beginning to bite earlier, before bed-nets are deployed. Malaria parasites can also be transmitted by blood transfusions, although this is rare.
''Plasmodium'' species
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 followed by P. vivax. P. falciparum in prevalent in Africa and accounts for the majority of deaths, while P. vivax is dominant outside Africa. Some cases have been documented of human infections with several species of Plasmodium from higher apes, but except for P. knowlesi—a zoonotic species that causes malaria in macaques—these are mostly of limited public health importance.Two species - P. vivax and P. ovale ''-'' form a dormant stage called a hypnozoite which can persist in the liver, even after drug treatment has eliminated the infection from the blood. These can reactivate after weeks or months and cause relapse of the disease.
Recurrent malaria
Symptoms of malaria can recur after varying symptom-free periods. Depending upon the cause, recurrence can be classified as either recrudescence, relapse, or reinfection. Recrudescence is when symptoms return after a symptom-free period due to failure to remove blood-stage parasites by adequate treatment. Relapse is when symptoms reappear after the parasites have been eliminated from the blood but have persisted as dormant hypnozoites in liver cells. Reinfection means that parasites were eliminated from the entire body but a new infection has established. Recurrence of infection within two weeks of treatment ending is typically attributed to treatment failure.Pathophysiology
Malaria infection develops via two phases: one that involves the liver, and one that involves red blood cells, or erythrocytes. 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. During this time, 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 first phase of infection is asymptomatic; the clinical symptoms of malaria are all associated with the merozoite stage of the life cycle. In this, the parasites multiply asexually within red blood cells, periodically breaking out to infect new ones. Within each infected erythrocyte, the parasite multiplies, consuming the cytoplasm as it does. After a period of 2 or 3 days, the erythrocyte bursts, releasing a number of new merozoites. This release of merozoites into the bloodstream, together with their waste products and fragments of erythrocyte, triggers fever and other symptoms which can be periodic and intense.
In some species of Plasmodium, some sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead, produce hypnozoites that remain dormant for periods ranging from several months 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 and P. ovale infections.