{{pp-semi-indef|small=yes}}
Malaria is a vector-borne
infectious diseaseAn infectious disease is a clinically evident disease resulting from the presence of pathogenic microbial agents, including pathogenic viruses, pathogenic bacteria, fungi, protozoa, multicellular parasites, and aberrant proteins known as prions...
caused by a eukaryotic
protistProtists , are a diverse group of eukaryotic microorganisms. Historically, protists were treated as the kingdom Protista but this group is no longer recognized in modern taxonomy...
of the genus
PlasmodiumPlasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was discovered in 1885 by Marchiafava and Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known species of...
. It is widespread in
tropicalThe tropics,the tropics are very hot. hi everyone! peace out!seated in the equatorial regions of the world, are limited in latitude by the Tropic of Cancer in the northern hemisphere at approximately 23°26' N latitude and the Tropic of Capricorn in the southern hemisphere at 23°26' S latitude...
and subtropical regions, including parts of the
AmericasThe Americas, or America, are lands in the Western hemisphere or New World, comprising the continents of North America and South America with their associated islands and regions. America may be ambiguous in English, as it is more commonly used to refer to the United States of America...
,
AsiaAsia is the world's largest and most populous continent, located in the eastern and northern hemispheres. It covers 8.6% of the earth's total surface area and with approximately 4 billion people, it hosts 60% of the world's current human population.Asia is traditionally defined as part of the...
, and
AfricaAfrica is the world's second-largest and second most-populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area. With a billion people in 61 territories, it accounts for about 14.8% of the...
. Each year, there are approximately 350–500 million cases of malaria, killing between one and three million people, the majority of whom are young children in
Sub-Saharan AfricaSub-Saharan Africa is a geographical term used to describe the area of the African continent which lies south of the Sahara, or those African countries which are fully or partially located south of the Sahara...
. Ninety percent of malaria-related deaths occur in Sub-Saharan Africa. Malaria is commonly associated with poverty, but is also a cause of poverty and a major hindrance to
economic developmentEconomic development is the increase in the standard of living of a nation's population associated with sustained growth from a simple, low-income economy to a modern, high-income economy...
.
Malaria is one of the most common infectious diseases and an enormous
public healthPublic health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals." It is concerned with threats to the overall health of a community based...
problem. Five species of the plasmodium parasite can infect humans; the most serious forms of the disease are caused by
Plasmodium falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
. Malaria caused by
Plasmodium vivaxPlasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring malaria, P. vivax is one of four species of malarial parasite that commonly infect humans. It is less virulent than Plasmodium falciparum, which is the deadliest of the four,...
,
Plasmodium ovalePlasmodium ovale is a species of parasitic protozoa that causes tertian malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax, which are responsible for most malaria. It is rare compared to these two parasites, and substantially less dangerous than P...
and
Plasmodium malariaePlasmodium malariae is a parasitic protozoa that causes malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that...
causes milder disease in humans that is not generally fatal. A fifth species,
Plasmodium knowlesiPlasmodium knowlesi is a primate malaria parasite commonly found in Southeast Asia. It causes malaria in long-tailed macaques , but it may also infect humans, either naturally or artificially....
, causes malaria in macaques but can also infect humans. This group of human-pathogenic
Plasmodium species is usually referred to as
malaria parasites.
Usually, people get malaria by being bitten by an infective female
Anopheles mosquitoAnopheles, , is a genus of mosquito. There are approximately 460 recognised species: while over 100 can transmit human malaria, only 30-40 commonly transmit parasites of the genus Plasmodium that cause malaria which affects humans in endemic areas...
. Only Anopheles mosquitoes can transmit malaria, and they must have been infected through a previous blood meal taken on an infected person. When a mosquito bites an infected person, a small amount of blood is taken, which contains microscopic malaria parasites. About one week later, when the mosquito takes its next blood meal, these parasites mix with the mosquito's saliva and are injected into the person being bitten. The parasites multiply within
red blood cellRed blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood. They take up oxygen in the lungs or gills and release it while squeezing through the body's capillaries. The cells are filled with hemoglobin, a...
s, causing symptoms that include symptoms of
anemiaAnemia is a decrease in normal number of red blood cells or less than the normal quantity of hemoglobin in the blood...
(light-headedness, shortness of breath,
tachycardiaTachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heartrate...
, etc.), as well as other general symptoms such as
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
, chills,
nauseaNausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
,
flu-like illnessInfluenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals. The name influenza is Italian and means "influence"...
, and, in severe cases,
comaIn medicine, a coma is a profound state of unconsciousness. A comatose person cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary actions....
, and death. Malaria transmission can be reduced by preventing mosquito bites with
mosquito netA mosquito net offers protection against mosquitos, flies, and other insects, and thus against diseases such as malaria. Its fine, see-through, mesh construction stops many insects from biting and disturbing the person using the net...
s and
insect repellentAn insect repellent is a substance applied to skin, clothing, or other surfaces which discourages insects from landing or climbing on that surface. There are also insect repellent products available based on sound production, particularly ultrasound...
s, or by mosquito control measures such as spraying
insecticideAn insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
s inside houses and draining standing water where mosquitoes lay their eggs. Work has been done on malaria vaccines with limited success and more exotic controls, such as genetic manipulation of mosquitoes to make them resistant to the parasite have also been considered.
Although some are under development, no
vaccineA vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains a small amount of an agent that resembles a microorganism...
is currently available for malaria that provides a high level of protection; preventive drugs must be taken continuously to reduce the risk of infection. These prophylactic drug treatments are often too expensive for most people living in
endemicIn epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
areas. Most adults from endemic areas have a degree of long-term infection, which tends to recur, and also possess partial
immunityImmunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
(resistance); the resistance reduces with time, and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. Malaria infections are treated through the use of
antimalarial drugAntimalarial drugs are designed to prevent or cure malaria. Some antimalarial agents, particularly chloroquine and hydroxychloroquine, are also used in the treatment of rheumatoid arthritis and lupus associated arthritis. There are many of these drugs currently on the market...
s, such as
quinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine....
or
artemisininArtemisinin is a drug used to treat multi-drug resistant strains of falciparum malaria. The compound is isolated from the plant Artemisia annua. Not all plants of this species contain artemisinin. Apparently it is only produced when the plant is subjected to certain conditions, most likely biotic...
derivatives. However, parasites have
evolvedIn biology, evolution is change in the genetic material of a population of organisms from one generation to the next. Though changes produced in any one generation are normally small, differences accumulate with each generation and can, over time, cause substantial changes in the population, a...
to be resistant to many of these drugs. Therefore, in some areas of the world, only a few drugs remain as effective treatments for malaria.
Symptoms
Symptoms of malaria include
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
,
shiveringShivering is a bodily function in response to early hypothermia in warm-blooded animals. When the core body temperature drops, the shivering reflex is triggered. Muscle groups around the vital organs begin to shake in small movements in an attempt to create warmth by expending energy...
,
arthralgiaArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
(joint pain),
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Undesired vomiting may result from many causes, ranging from gastritis or poisoning to brain tumors, or elevated intracranial pressure...
,
anemiaAnemia is a decrease in normal number of red blood cells or less than the normal quantity of hemoglobin in the blood...
(caused by
hemolysisHemolysis —from the Greek Hemo-, Greek meaning blood, -lysis, meaning to break open—is the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid ....
),
hemoglobinuriaIn medicine, hemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is often associated with hemolytic anemia, in which red blood cells are destroyed, thereby increasing levels of free plasma hemoglobin...
,
retinal damageRetinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
, and
convulsionA convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptical seizure, the term convulsion is sometimes used as a synonym for seizure...
s. The classic symptom of malaria is cyclical occurrence of sudden coldness followed by
rigorRigor is a shaking occurring during a high fever. It occurs because cytokines and prostaglandins are released as part of an immune response and increase the set point for body temperature in the hypothalamus....
and then fever and sweating lasting four to six hours, occurring every two days in
P. vivax and
P. ovale infections, while every three for
P. malariae.
P. falciparum can have recurrent fever every 36–48 hours or a less pronounced and almost continuous fever. For reasons that are poorly understood, but that may be related to high
intracranial pressureIntracranial pressure is the pressure in the cranium and thus in the brain tissue and cerebrospinal fluid ; this pressure is exerted on the brain's intracranial blood circulation vessels. ICP is maintained in a tight normal range dynamically, through the production and absorption of CSF and...
, children with malaria frequently exhibit
abnormal posturingAbnormal 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 causes the working set of muscles to contract. The posturing...
, a sign indicating severe brain damage. Malaria has been found to cause cognitive impairments, especially in children. It causes widespread
anemiaAnemia is a decrease in normal number of red blood cells or less than the normal quantity of hemoglobin in the blood...
during a period of rapid brain development and also direct brain damage. This neurologic damage results from cerebral malaria to which children are more vulnerable. Cerebral malaria is associated with retinal whitening, which may be a useful clinical sign in distinguishing it from other causes of fever.
| Species |
Appearance |
Periodicity |
Persistent in liver? |
Plasmodium vivaxPlasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring malaria, P. vivax is one of four species of malarial parasite that commonly infect humans. It is less virulent than Plasmodium falciparum, which is the deadliest of the four,...
|
|
tertian |
yes |
Plasmodium ovalePlasmodium ovale is a species of parasitic protozoa that causes tertian malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax, which are responsible for most malaria. It is rare compared to these two parasites, and substantially less dangerous than P...
|
|
tertian |
yes |
Plasmodium falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
|
|
tertian |
no |
Plasmodium malariaePlasmodium malariae is a parasitic protozoa that causes malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that...
|
|
quartan |
no |
Severe malaria is almost exclusively caused by
P. falciparum infection and usually arises 6–14 days after infection. Consequences of severe malaria include
comaIn medicine, a coma is a profound state of unconsciousness. A comatose person cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary actions....
and death if untreated—young children and pregnant women are especially vulnerable.
SplenomegalySplenomegaly is an enlargement of the spleen, which usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, the other three being cytopenia, normal or hyperplastic bone marrow, and a response to splenectomy...
(enlarged spleen), severe
headacheIn medicine a headache or cephalalgia is a symptom of a number of different conditions of the head. Some of the causes are benign while others are medical emergencies.There are a number of different classification systems for headaches...
, cerebral
ischemiaIn medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue...
,
hepatomegalyHepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
(enlarged liver),
hypoglycemiaHypoglycemia or hypoglycaemia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood" Hypoglycemia or hypoglycaemia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally...
, and hemoglobinuria with
renal failureRenal failure or kidney failure is a situation in which the kidneys fail to function adequately. It is divided into acute and chronic forms; either form may be due to a large number of other medical problems....
may occur. Renal failure may cause
blackwater feverBlackwater fever is a complication of malaria characterized by intravascular haemolysis, haemoglobinuria and kidney failure. Blackwater fever is caused by heavy parasitization of red blood cells with Plasmodium falciparum...
, where hemoglobin from lysed red blood cells leaks into the urine. Severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease fatality rates can exceed 20%, even with intensive care and treatment. In endemic areas, treatment is often less satisfactory and the overall fatality rate for all cases of malaria can be as high as one in ten. Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.
Chronic malaria is seen in both
P. vivax and
P. ovale, but not in
P. falciparum. Here, the disease can relapse months or years after exposure, due to the presence of latent parasites in the liver. Describing a case of malaria as cured by observing the disappearance of parasites from the bloodstream can, therefore, be deceptive. The longest incubation period reported for a
P. vivax infection is 30 years. Approximately one in five of
P. vivax malaria cases in
temperateIn geography, temperate or tepid latitudes of the globe lie between the tropics and the polar circles. The changes in these regions between summer and winter are generally mild, rather than extreme hot or cold. But in continental areas, such as central North America the variations between summer...
areas involve overwintering by hypnozoites (i.e., relapses begin the year after the mosquito bite).
Causes
Malaria parasites
Malaria parasites are members of the genus
PlasmodiumPlasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was discovered in 1885 by Marchiafava and Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known species of...
(phylum
ApicomplexaThe Apicomplexa are a large group of protists, most of which possess a unique organelle called apicoplast and an apical complex structure involved in penetrating a host's cell. They are unicellular, spore-forming, and exclusively parasites of animals. Motile structures such as flagella or...
). In humans malaria is caused by
P. falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
,
P. malariaePlasmodium malariae is a parasitic protozoa that causes malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that...
,
P. ovalePlasmodium ovale is a species of parasitic protozoa that causes tertian malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax, which are responsible for most malaria. It is rare compared to these two parasites, and substantially less dangerous than P...
,
P. vivaxPlasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring malaria, P. vivax is one of four species of malarial parasite that commonly infect humans. It is less virulent than Plasmodium falciparum, which is the deadliest of the four,...
and
P. knowlesiPlasmodium knowlesi is a primate malaria parasite commonly found in Southeast Asia. It causes malaria in long-tailed macaques , but it may also infect humans, either naturally or artificially....
.
P. falciparum is the most common cause of infection and is responsible for about 80% of all malaria cases, and is also responsible for about 90% of the deaths from malaria. Parasitic
Plasmodium species also infect birds, reptiles, monkeys, chimpanzees and rodents. There have been documented human infections with several simian species of malaria, namely
P. knowlesi,
P. inui,
P. cynomolgi,
P. simiovale,
P. brazilianum,
P. schwetzi and
P. simium; however, with the exception of
P. knowlesi, these are mostly of limited public health importance. Although
avian malariaAvian malaria is a parasitic disease affecting birds.-Etiology:Avian malaria is most notably caused by Plasmodium relictum, a protist that infects birds in tropical regions...
can kill chickens and turkeys, this disease does not cause serious economic losses to poultry farmers. However, since being accidentally introduced by humans it has decimated the
endemic birds of HawaiiThis article is one of a series providing information about endemism among birds in the World's various zoogeographic zones. For an overview of this subject see Endemism in birds....
, which evolved in its absence and lack any resistance to it.
Mosquito vectors and the Plasmodium life cycle
The parasite's primary (definitive) hosts and transmission vectors are female
mosquitoMosquito is a common insect in the family Culicidae...
es of the
AnophelesAnopheles, , is a genus of mosquito. There are approximately 460 recognised species: while over 100 can transmit human malaria, only 30-40 commonly transmit parasites of the genus Plasmodium that cause malaria which affects humans in endemic areas...
genus. Young mosquitoes first ingest the malaria parasite by feeding on an infected human carrier and the infected
Anopheles mosquitoes carry
Plasmodium sporozoiteIn the life-cycle of apicomplexan protozoa, sporozoites are cells that infect new hosts. In the parasites that cause malaria , for instance, the sporozoites are cells that develop in the mosquito's salivary glands, leave the mosquito during a blood meal, and enter the liver where they multiply...
s in their
salivary glandThe salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into glucose...
s. A mosquito becomes infected when it takes a blood meal from an infected human. Once ingested, the parasite gametocytes taken up in the blood will further differentiate into male or female gametes and then fuse in the mosquito gut. This produces an
ookineteAn ookinete is a zygote of protozoans such as the malaria organism. It is capable of moving spontaneously. It penetrates the stomach of mosquitos to form a thick-walled structure known as an oocyst under the mosquito's outer gut lining.See http://dictionary.reference.com/search?q=ookinete...
that penetrates the gut lining and produces an
oocystAn oocyst is the thick-walled spore phase of certain protists , such as Cryptosporidium and Toxoplasma. This state can survive for lengthy periods outside a host and is very resistant....
in the gut wall. When the oocyst ruptures, it releases sporozoites that migrate through the mosquito's body to the salivary glands, where they are then ready to infect a new human host. This type of transmission is occasionally referred to as anterior station transfer. The sporozoites are injected into the skin, alongside saliva, when the mosquito takes a subsequent blood meal.
Only female mosquitoes feed on blood, thus males do not transmit the disease. The females of the
Anopheles genus of mosquito prefer to feed at night. They usually start searching for a meal at dusk, and will continue throughout the night until taking a meal. Malaria parasites can also be transmitted by
blood transfusionBlood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery...
s, although this is rare.
Pathogenesis
Malaria in humans develops via two phases: an exoerythrocytic and an erythrocytic phase. The exoerythrocytic phase involves infection of the hepatic system, or liver, whereas the erythrocytic phase involves infection of the erythrocytes, or red blood cells. When an infected mosquito pierces a person's skin to take a blood meal,
sporozoiteIn the life-cycle of apicomplexan protozoa, sporozoites are cells that infect new hosts. In the parasites that cause malaria , for instance, the sporozoites are cells that develop in the mosquito's salivary glands, leave the mosquito during a blood meal, and enter the liver where they multiply...
s in the mosquito's saliva enter the bloodstream and migrate to the
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Within 30 minutes of being introduced into the human host, the sporozoites infect
hepatocyteHepatocytes make up 70-80% of the cytoplasmic mass of the liver.These cells are involved in protein synthesis, protein storage and transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, and detoxification, modification and excretion of exogenous and endogenous...
s, multiplying asexually and asymptomatically for a period of 6–15 days. Once in the liver, these organisms differentiate to yield thousands of
merozoiteA merozoite is a daughter cell of a protozoan parasite. Merozoites are the result of asexual reproduction . In coccidiosis, merozoites form the first phase of the internal life cycle of coccidian.In malaria, these spores infect red blood cells and then rapidly reproduce asexually...
s, which, following rupture of their host cells, escape into the blood and infect
red blood cellRed blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood. They take up oxygen in the lungs or gills and release it while squeezing through the body's capillaries. The cells are filled with hemoglobin, a...
s, thus beginning 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 hosts 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 and
P. ovale sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant for periods ranging from several months (6–12 months is typical) to as long as three years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in these two species of malaria.
The parasite is relatively protected from attack by the body's
immune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumour cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
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
spleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells, holds a reserve in case of hemorrhagic shock, especially in...
. To avoid this fate, the
P. falciparum parasite displays adhesive
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s 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. This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria.
High endothelial venulesHigh endothelial venules are specialized post-capillary venous swellings characterized by simple cuboidal cells as opposed to simple Squamous cells found in regular venules...
(the smallest branches of the circulatory system) can be blocked by the attachment of masses of these infected red blood cells. The blockage of these vessels causes symptoms such as in placental and cerebral malaria. In cerebral malaria the sequestrated red blood cells can breach the
blood brain barrierThe blood-brain barrier is a separation of circulating blood and cerebrospinal fluid maintained by the choroid plexus in the central nervous system . Endothelial cells restrict the diffusion of microscopic objects The blood-brain barrier (BBB) is a separation of circulating blood and...
possibly leading to coma.
Although the red blood cell surface adhesive proteins (called PfEMP1, for
Plasmodium falciparum erythrocyte membrane protein 1) are exposed to the immune system, they do not serve as good immune targets because of their extreme diversity; there are at least 60 variations of the protein within a single parasite and perhaps limitless versions within parasite populations. Like a thief changing disguises or a spy with multiple passports, the parasite switches between a broad repertoire of PfEMP1 surface proteins, thus staying one step ahead of the pursuing immune system.
Some merozoites turn into male and female
gametocyteA 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....
s. If a mosquito pierces the skin of an infected person, it potentially picks up gametocytes within the blood. Fertilization and sexual recombination of the parasite occurs in the mosquito's gut, thereby defining the mosquito as the definitive host of the disease. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially attractive to the mosquitoes, and malaria in pregnant women is an important cause of
stillbirthA stillbirth occurs when a fetus which has died, in the uterus or during labor or delivery, exits a woman's body. The term is often used in distinction to live birth or miscarriage. Most stillbirths occur in full term pregnancies....
s, infant mortality and low birth weight, particularly in
P. falciparum infection, but also in other species infection, such as
P. vivax.
Diagnosis
{{further|
Blood filmA blood film or peripheral blood smear is a microscope slide made from a drop of blood, that allows the cells to be examined microscopically...
}}
Since Charles Laveran first visualised the malaria parasite in blood in 1880, the mainstay of malaria diagnosis has been the microscopic examination of blood.
Fever and septic shock are commonly misdiagnosed as severe malaria in
AfricaAfrica is the world's second-largest and second most-populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area. With a billion people in 61 territories, it accounts for about 14.8% of the...
, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas,
parasitemiaParasitemia is the quantitative content of parasites in the blood. It is used as a measurement of parasite load in the organism and an indication of the degree of an active parasitic infection...
does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. Recent investigations suggest that malarial
retinopathyRetinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
is better (collective sensitivity of 95% and specificity of 90%) than any other clinical or laboratory feature in distinguishing malarial from non-malarial
comaIn medicine, a coma is a profound state of unconsciousness. A comatose person cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary actions....
.
Although blood is the sample most frequently used to make a diagnosis, both saliva and urine have been investigated as alternative, less invasive specimens.
Symptomatic diagnosis
Areas that cannot afford even simple laboratory diagnostic tests often use only a history of subjective fever as the indication to treat for malaria. Using Giemsa-stained blood smears from children in Malawi, one study showed that when clinical predictors (rectal temperature, nailbed pallor, and splenomegaly) were used as treatment indications, rather than using only a history of subjective fevers, a correct diagnosis increased from 21% to 41% of cases and unnecessary treatment for malaria was significantly decreased.
Microscopic examination of blood films
{{Details3|
P. falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
,
P. vivaxPlasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring malaria, P. vivax is one of four species of malarial parasite that commonly infect humans. It is less virulent than Plasmodium falciparum, which is the deadliest of the four,...
,
P. ovalePlasmodium ovale is a species of parasitic protozoa that causes tertian malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax, which are responsible for most malaria. It is rare compared to these two parasites, and substantially less dangerous than P...
,
P. malariaePlasmodium malariae is a parasitic protozoa that causes malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that...
|individual parasites}}
The most economic, preferred, and reliable diagnosis of malaria is microscopic examination of
blood filmA blood film or peripheral blood smear is a microscope slide made from a drop of blood, that allows the cells to be examined microscopically...
s because each of the four major parasite species has distinguishing characteristics. Two sorts of blood film are traditionally used. Thin films are similar to usual blood films and allow species identification because the parasite's appearance is best preserved in this preparation. Thick films allow the microscopist to screen a larger volume of blood and are about eleven times more sensitive than the thin film, so picking up low levels of infection is easier on the thick film, but the appearance of the parasite is much more distorted and therefore distinguishing between the different species can be much more difficult. With the pros and cons of both thick and thin smears taken into consideration, it is imperative to utilize both smears while attempting to make a definitive diagnosis.
From the thick film, an experienced microscopist can detect parasite levels (or
parasitemiaParasitemia is the quantitative content of parasites in the blood. It is used as a measurement of parasite load in the organism and an indication of the degree of an active parasitic infection...
) down to as low as 0.0000001% of red blood cells. Diagnosis of species can be difficult because the early trophozoites ("ring form") of all four species look identical and it is never possible to diagnose species on the basis of a single ring form; species identification is always based on several trophozoites.
Field tests
In areas where microscopy is not available, or where laboratory staff are not experienced at malaria diagnosis, there are
antigen detection testsMalaria antigen detection tests are a group of commercially available tests that allow the rapid diagnosis of malaria by people who are not otherwise skilled in traditional laboratory techniques for diagnosing malaria or in situations where such equipment is not available. There are currently over...
that require only a drop of blood. Immunochromatographic tests (also called: Malaria Rapid Diagnostic Tests, Antigen-Capture Assay or "Dipsticks") have been developed, distributed and fieldtested. These tests use finger-stick or venous blood, the completed test takes a total of 15–20 minutes, and a laboratory is not needed. The threshold of detection by these rapid diagnostic tests is in the range of 100 parasites/µl of blood compared to 5 by thick film microscopy. The first rapid diagnostic tests were using P. falciparum
glutamate dehydrogenaseGlutamate dehydrogenase is an enzyme, present in mitochondria of eukaryotes, as are some of the other enzymes required for urea synthesis, that converts glutamate to α-Ketoglutarate, and vice versa...
as antigen.
PGluDH was soon replaced by P.falciparum
lactate dehydrogenaseLactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes with each acting on either D-lactate or L-lactate...
, a 33 kDa oxidoreductase [EC 1.1.1.27]. It is the last enzyme of the glycolytic pathway, essential for ATP generation and one of the most abundant enzymes expressed by P.falciparum. PLDH does not persist in the blood but clears about the same time as the parasites following successful treatment. The lack of antigen persistence after treatment makes the pLDH test useful in predicting treatment failure. In this respect, pLDH is similar to pGluDH. The OptiMAL-IT assay can distinguish between P. falciparum and P. vivax because of antigenic differences between their pLDH isoenzymes.
OptiMAL-IT will reliably detect
falciparum down to 0.01%
parasitemiaParasitemia is the quantitative content of parasites in the blood. It is used as a measurement of parasite load in the organism and an indication of the degree of an active parasitic infection...
and non-
falciparum down to 0.1%.
Paracheck-Pf will detect parasitemias down to 0.002% but will not distinguish between
falciparum and non-
falciparum malaria. Parasite nucleic acids are detected using
polymerase chain reactionIn molecular biology, the polymerase chain reaction is a technique to amplify a single or few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence...
. This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory. Moreover, levels of parasitemia are not necessarily correlative with the progression of disease, particularly when the parasite is able to adhere to blood vessel walls. Therefore more sensitive, low-tech diagnosis tools need to be developed in order to detect low levels of parasitaemia in the field. Areas that cannot afford even simple laboratory diagnostic tests often use only a history of subjective fever as the indication to treat for malaria. Using Giemsa-stained blood smears from children in Malawi, one study showed that unnecessary treatment for malaria was significantly decreased when clinical predictors (rectal temperature, nailbed pallor, and splenomegaly) were used as treatment indications, rather than the current national policy of using only a history of subjective fevers (sensitivity increased from 21% to 41%).
Molecular methods
Molecular methods are available in some clinical laboratories and rapid real-time assays (for example,
QT-NASBAIn molecular biology, real-time polymerase chain reaction, also called quantitative real time polymerase chain reaction or kinetic polymerase chain reaction, is a laboratory technique based on the polymerase chain reaction, which is used to amplify and simultaneously quantify a targeted DNA molecule...
based on the polymerase chain reaction) are being developed with the hope of being able to deploy them in endemic areas.
Rapid antigen tests
OptiMAL-IT will reliably detect
falciparum down to 0.01%
parasitemiaParasitemia is the quantitative content of parasites in the blood. It is used as a measurement of parasite load in the organism and an indication of the degree of an active parasitic infection...
and non-
falciparum down to 0.1%.
Paracheck-Pf will detect parasitemias down to 0.002% but will not distinguish between
falciparum and non-
falciparum malaria. Parasite nucleic acids are detected using
polymerase chain reactionIn molecular biology, the polymerase chain reaction is a technique to amplify a single or few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence...
. This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory. Moreover, levels of parasitemia are not necessarily correlative with the progression of disease, particularly when the parasite is able to adhere to blood vessel walls. Therefore more sensitive, low-tech diagnosis tools need to be developed in order to detect low levels of parasitaemia in the field.
Prevention
Methods used to prevent the spread of disease, or to protect individuals in areas where malaria is endemic, include prophylactic drugs, mosquito eradication, and the prevention of mosquito bites.
The continued existence of malaria in an area requires a combination of high human population density, high 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 will sooner or later disappear from that area, as happened in
North AmericaNorth America is the northern continent of the Americas, situated in the Earth's northern hemisphere and in the western hemisphere. It is bordered on the north by the Arctic Ocean, on the east by the North Atlantic Ocean, on the southeast by the Caribbean Sea, and on the west by the North Pacific...
,
EuropeEurope is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally divided from Asia to its east by the water divide of the Ural Mountains, the Ural River, the Caspian Sea, the Caucasus Mountains , and the Black Sea to the southeast...
and much of
Middle EastThe Middle East is a region that spans southwestern Asia, southeastern Europe, and northeastern Africa. It has no clear boundaries, often used as a synonym to Near East, in opposition to Far East...
. However, unless the parasite is eliminated from the whole world, it could become re-established if conditions revert to a combination that favors the parasite's reproduction. Many countries are seeing an increasing number of imported malaria cases due to extensive travel and migration. (See
AnophelesAnopheles, , is a genus of mosquito. There are approximately 460 recognised species: while over 100 can transmit human malaria, only 30-40 commonly transmit parasites of the genus Plasmodium that cause malaria which affects humans in endemic areas...
.)
There is currently no
vaccineVaccination is the administration of antigenic material to produce immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by a pathogen. Vaccination is generally considered to be the most effective and cost-effective method of preventing infectious diseases...
that will prevent malaria, but this is an active field of research.
Many researchers argue that prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the capital costs required are out of reach of many of the world's poorest people. Economic adviser
Jeffrey SachsJeffrey David Sachs is an American economist and Director of the Earth Institute at Columbia University...
estimates that malaria can be controlled for US$3 billion in aid per year. It has been argued that, in order to meet the
Millennium Development GoalsThe Millennium Development Goals are eight international development goals that 192 United Nations member states and at least 23 international organizations have agreed to achieve by the year 2015...
, money should be redirected from
HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid,...
/
AIDSAcquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus ....
treatment to malaria prevention, which for the same amount of money would provide greater benefit to African economies.
The distribution of funding varies among countries. Countries with large populations do not receive the same amount of support. The 34 countries that received a per capita annual support of less than $1 included some of the poorest countries in Africa.
Brazil, Eritrea, India, and Vietnam have, unlike many other developing nations, successfully reduced the malaria burden. Common success factors included conducive country conditions, a targeted technical approach using a package of effective tools, data-driven decision-making, active leadership at all levels of government, involvement of communities, decentralized implementation and control of finances, skilled technical and managerial capacity at national and sub-national levels, hands-on technical and programmatic support from partner agencies, and sufficient and flexible financing.
Vector control
{{further|
Mosquito controlMosquito control manages the population of mosquitoes to reduce their damage to human health, economies, and enjoyment. Mosquito control is a vital public-health practice throughout the world and especially in the tropics because mosquitoes spread many diseases, such as malaria.Mosquito-control...
}}
Efforts to
eradicateEradication is the reduction of an infectious disease's prevalence in the global human or animal host population to zero. A number of world organizations together with local governments are working to fully eradicate various diseases...
malaria by eliminating mosquitoes have been successful in some areas. Malaria was once common in the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
and southern
EuropeEurope is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally divided from Asia to its east by the water divide of the Ural Mountains, the Ural River, the Caspian Sea, the Caucasus Mountains , and the Black Sea to the southeast...
, but vector control programs, in conjunction with the monitoring and treatment of infected humans, eliminated it from those regions. In some areas, the draining of wetland breeding grounds and better sanitation were adequate. Malaria was eliminated from the northern parts of the USA in the early 20th century by such methods, and the use of the
pesticideA pesticide is a substance or mixture of substances used to kill a pest.A pesticide is any substance or mixture of substance intended for:- preventing, destroying, repelling or mitigating any pest....
DDTDDT is one of the most well-known synthetic pesticides. It is a chemical with a long, unique, and controversial history....
eliminated it from the South by 1951. In 2002, there were 1,059 cases of malaria reported in the US, including eight deaths, but in only five of those cases was the disease contracted in the United States.
Before DDT, malaria was successfully eradicated or controlled also in several tropical areas by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larva stages, for example by filling or applying oil to places with standing water. These methods have seen little application in Africa for more than half a century. In the 1950s and 1960s, there was a major public health effort to eradicate malaria worldwide by selectively targeting mosquitoes in areas where malaria was rampant. However, these efforts have so far failed to eradicate malaria in many parts of the developing world—the problem is most prevalent in Africa.
Sterile insect techniqueSterile insect technique is a method of biological control, whereby millions of sterile insects are released. The released insects are normally male as it is the female that causes the damage, usually by laying eggs in the crop, or, in the case of mosquitoes, taking a bloodmeal from humans. The...
is emerging as a potential mosquito control method. Progress towards transgenic, or
genetically modifiedA genetically modified organism or genetically engineered organism is an organism whose genetic material has been altered using genetic engineering techniques. These techniques, generally known as recombinant DNA technology, use DNA molecules from different sources, which are combined into one...
, insects suggest that wild mosquito populations could be made malaria-resistant. Researchers at
Imperial College LondonImperial College London is a British university in London specialising in science, engineering, medicine and business....
created the world's first transgenic malaria mosquito, with the first plasmodium-resistant species announced by a team at
Case Western Reserve UniversityCase Western Reserve University is a private research university located in Cleveland, Ohio, USA...
in
OhioOhio is a Midwestern state of the United States. The thirty-fourth largest state by area in the U.S., it is the seventh-most populous with nearly 11.5 million residents...
in 2002. Successful replacement of current populations with a new genetically modified population, relies upon a drive mechanism, such as transposable elements to allow for non-Mendelian inheritance of the gene of interest. However, this approach contains many difficulties and success is a distant prospect. An even more futuristic method of vector control is the idea that
laserA laser is a device that emits light through a process called stimulated emission. Laser light is usually spatially coherent, which means that the light either is emitted in a narrow, low-divergence beam, or can be converted into one with the help of optical components such as lenses...
s could be used to kill flying mosquitoes.
Prophylactic drugs
{{Main|Malaria prophylaxis}}
Several drugs, most of which are also used for treatment of malaria, can be taken preventively. Generally, these drugs are taken daily or weekly, at a lower dose than would be used for treatment of a person who had actually contracted the disease. Use of prophylactic drugs is seldom practical for full-time residents of malaria-endemic areas, and their use is usually restricted to short-term visitors and travelers to malarial regions. This is due to the cost of purchasing the drugs, negative
side effectIn medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect, and may result from an unsuitable or incorrect dosage or...
s from long-term use, and because some effective anti-malarial drugs are difficult to obtain outside of wealthy nations.
QuinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine....
was used starting in the 17th century as a prophylactic against malaria. The development of more effective alternatives such as
quinacrineQuinacrine is a drug with a number of different medical applications.-Uses:Its main effects are as an antiprotozoal, antirheumatic and an intrapleural sclerosing agent, although it is not commercially available in the United States or Canada.Antiprotozoal use include targeting Giardiasis, where...
,
chloroquineChloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-Uses:* It has long been used in the treatment or prevention of malaria. After the malaria parasite Plasmodium falciparum started to develop widespread resistance to chloroquine, new potential utilisations of...
, and
primaquinePrimaquine is a medication used in the treatment of malaria and Pneumocystis pneumonia. It is a member of the 8-aminoquinoline group of drugs that includes tafenoquine and pamaquine.-Radical cure:...
in the 20th century reduced the reliance on quinine. Today, quinine is still used to treat chloroquine resistant
Plasmodium falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
, as well as severe and cerebral stages of malaria, but is not generally used for prophylaxis.
Modern drugs used preventively include
mefloquineMefloquine is an orally-administered antimalarial drug used as a prophylaxis against and treatment for malaria. It also goes by the trade name Lariam or Mefaquin and chemical name mefloquine hydrochloride . Mefloquine was developed in the 1970s at the Walter Reed Army Institute of Research in the...
(
Lariam),
doxycyclineDoxycycline is a member of the tetracycline antibiotics group and is commonly used to treat a variety of infections. Doxycycline is a semi-synthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin received...
(available generically), and the combination of
atovaquoneAtovaquone is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about US$2.13 per standard 250 mg. tablet...
and
proguanilProguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
hydrochloride (
Malarone). The choice of which drug to use depends on which drugs the parasites in the area are
resistantDrug resistance is the reduction in effectiveness of a drug in curing a disease or improving a patient's symptoms. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance...
to, as well as side-effects and other considerations. The prophylactic effect does not begin immediately upon starting taking the drugs, so people temporarily visiting malaria-endemic areas usually begin taking the drugs one to two weeks before arriving and must continue taking them for 4 weeks after leaving (with the exception of atovaquone proguanil that only needs be started 2 days prior and continued for 7 days afterwards).
The use of prophylactic drugs where malaria-bearing mosquitoes are present may encourage the development of partial immunity.
Indoor residual spraying
{{main|Indoor residual spraying|DDT use against malaria}}
Indoor residual spraying (IRS) is the practice of spraying insecticides on the interior walls of homes in malaria affected areas. After feeding, many mosquito species rest on a nearby surface while digesting the bloodmeal, so if the walls of dwellings have been coated with insecticides, the resting mosquitos will be killed before they can bite another victim, transferring the malaria parasite.
The first pesticide used for IRS was
DDTDDT is one of the most well-known synthetic pesticides. It is a chemical with a long, unique, and controversial history....
. Although it was initially used exclusively to combat malaria, its use quickly spread to
agricultureAgriculture is the production of food and goods through farming and forestry. Agriculture was the key development that led to the rise of human civilization, with the husbandry of domesticated animals and plants creating food surpluses that enabled the development of more densely populated and...
. In time, pest-control, rather than disease-control, came to dominate DDT use, and this large-scale agricultural use led to the
evolutionIn biology, evolution is change in the genetic material of a population of organisms from one generation to the next. Though changes produced in any one generation are normally small, differences accumulate with each generation and can, over time, cause substantial changes in the population, a...
of resistant mosquitoes in many regions. The DDT resistance shown by Anopheles mosquitoes can be compared to antibiotic resistance shown by bacteria. The overuse of anti-bacterial soaps and antibiotics led to antibiotic resistance in bacteria, similar to how overspraying of DDT on crops led to DDT resistance in Anopheles mosquitoes. 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. Since the use of DDT has been limited or banned for agricultural use for some time, DDT may now be more effective as a method of disease-control.
Although DDT has never been banned for use in malaria control and there are several other insecticides suitable for IRS, some advocates have claimed that bans are responsible for tens of millions of deaths in tropical countries where DDT had once been effective in controlling malaria. Furthermore, most of the problems associated with DDT use stem specifically from its industrial-scale application in agriculture, rather than its use in
public healthPublic health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals." It is concerned with threats to the overall health of a community based...
.
The
World Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health...
(WHO) currently advises the use of 12 different insecticides in IRS operations. These include DDT and a series of alternative insecticides (such as the pyrethroids
permethrinPermethrin is a common synthetic chemical, widely used as an insecticide, acaricide, and insect repellent. It belongs to the family of synthetic chemicals called pyrethroids and functions as a neurotoxin, affecting neuron membranes by prolonging sodium channel activation. It is not known to...
and
deltamethrinDeltamethrin is a pyrethroid ester insecticide.-Usage:Deltamethrin products are among some of the most popular and widely used insecticides in the world and have become very popular with pest control operators and individuals in the United States in the past five years. This material is a member of...
), to combat malaria in areas where mosquitoes are DDT-resistant and to slow the evolution of resistance. This public health use of small amounts of DDT is permitted under the
Stockholm ConventionStockholm Convention on Persistent Organic Pollutants is an international environmental treaty that aims to eliminate or restrict the production and use of persistent organic pollutants .- History :...
on
Persistent Organic PollutantPersistent organic pollutants are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes...
s (POPs), which prohibits the agricultural use of DDT. However, because of its legacy, many developed countries discourage DDT use even in small quantities.
One problem with all forms of Indoor Residual Spraying is insecticide
resistancePesticide resistance is the adaptation of pest species targeted by a pesticide resulting in decreased susceptibility to that chemical. In other words, pests develop a resistance to a chemical through selection; after they are exposed to a pesticide for a prolonged period it no longer kills them as...
via evolution of mosquitos. According to a study published on Mosquito Behavior and Vector Control, mosquito species that are affected by IRS are endophilic species (species that tend to rest and live indoors), and due to the irritation caused by spraying, their evolutionary descendants are trending towards becoming exophilic (species that tend to rest and live out of doors), meaning that they are not as affected—if affected at all—by the IRS, rendering it somewhat useless as a defense mechanism.
Mosquito nets and bedclothes
Mosquito nets help keep mosquitoes away from people and greatly reduce the infection and transmission of malaria. The nets are not a perfect barrier and they are often treated with an insecticide designed to kill the mosquito before it has time to search for a way past the net. Insecticide-treated nets (ITN) are estimated to be twice as effective as untreated nets, and offer greater than 70% protection compared with no net.. Although ITN are proven to be very effective against malaria, less than 2% of children in urban areas in Sub-Saharan Africa are protected by ITNs. Since the
AnophelesAnopheles, , is a genus of mosquito. There are approximately 460 recognised species: while over 100 can transmit human malaria, only 30-40 commonly transmit parasites of the genus Plasmodium that cause malaria which affects humans in endemic areas...
mosquitoes feed at night, the preferred method is to hang a large "bed net" above the center of a bed such that it drapes down and covers the bed completely.
The distribution of mosquito nets impregnated with insecticides such as
permethrinPermethrin is a common synthetic chemical, widely used as an insecticide, acaricide, and insect repellent. It belongs to the family of synthetic chemicals called pyrethroids and functions as a neurotoxin, affecting neuron membranes by prolonging sodium channel activation. It is not known to...
or deltamethrin has been shown to be an extremely effective method of malaria prevention, and it is also one of the most cost-effective methods of prevention. These nets can often be obtained for around $2.50–$3.50 (2–3 euros) from the
United NationsThe United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and the achieving of world peace...
, the World Health Organization (WHO), and others. ITNs have been shown to be the most cost-effective prevention method against malaria and are part of WHO’s Millennium Development Goals (MDGs).
For maximum effectiveness, the nets should be re-impregnated with insecticide every six months. This process poses a significant logistical problem in rural areas. New technologies like Olyset or DawaPlus allow for production of long-lasting insecticidal mosquito nets (LLINs), which release insecticide for approximately 5 years, and cost about US$5.50. ITNs protect people sleeping under the net and simultaneously kill mosquitoes that contact the net. Some protection is also provided to others by this method, including people sleeping in the same room but not under the net.
While distributing mosquito nets is a major component of malaria prevention, community education and awareness on the dangers of malaria are associated with distribution campaigns to make sure people who receive a net know how to use it. "Hang Up" campaigns such as the ones conducted by volunteers of the
International Red Cross and Red Crescent MovementThe International Red Cross and Red Crescent Movement is an international humanitarian movement with approximately 97 million volunteers worldwide which started to protect human life and health, to ensure respect for the human being, and to prevent and alleviate human suffering, without any...
consist of visiting households that received a net at the end of the campaign or just before the rainy season, ensuring that the net is being used properly and that the people most vulnerable to malaria, such as young children and the elderly, sleep under it. A study conducted by the
CDCThe Centers for Disease Control and Prevention is a United States federal agency under the Department of Health and Human Services based in Atlanta, Georgia. It works to protect public health and safety by providing information to enhance health decisions, and it promotes health through...
in
Sierra LeoneSierra Leone , officially the Republic of Sierra Leone, is a country in West Africa. It is bordered by Guinea in the north, Liberia in the southeast, and the Atlantic Ocean in the southwest. Sierra Leone covers a total area of and has a population estimated at 6.4 million...
showed a 22 percent increase in net utilization following a personal visit from a volunteer living in the same community promoting net usage. A study in
TogoTogo is a country in West Africa bordering Ghana to the west, Benin to the east and Burkina Faso to the north. It extends south to the Gulf of Guinea, on which the capital Lomé is located...
showed similar improvements.
The cost of treating malaria is high relative to income and the illness results in lost wages. Mosquito nets are often unaffordable to people in developing countries, especially for those most at risk. Only 1 out of 20 people in Africa own a bed net. Nets are also often distributed though vaccine campaigns using voucher subsidies, such as the measles campaign for children.
A study among Afghan refugees in Pakistan found that treating top-sheets and chaddars (head coverings) with permethrin has similar effectiveness to using a treated net, but is much cheaper. Another alternative approach uses spores of the
fungusA fungus is any member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. The Fungi are classified as a kingdom that is separate from plants, animals and bacteria...
Beauveria bassianaBeauveria bassiana is a fungus that grows naturally in soils throughout the world and acts as a parasite on various insect species, causing white muscardine disease; it thus belongs to the entomopathogenic fungi...
, sprayed on walls and bed nets, to kill mosquitoes. While some mosquitoes have developed resistance to chemicals, they have not been found to develop a resistance to fungal infections.
Vaccination
{{further|
Malaria vaccineMalaria vaccines are an area of intensive research, however, no effective vaccine has yet been introduced into clinical practice.The global burden of P. falciparum malaria increased through the 1990s due to the development of drug-resistant parasites and insecticide-resistant mosquitoes; this is...
}}
Immunity (or, more accurately, tolerance) does occur naturally, but only in response to repeated infection with multiple strains of malaria.
VaccinesVaccination is the administration of antigenic material to produce immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by a pathogen. Vaccination is generally considered to be the most effective and cost-effective method of preventing infectious diseases...
for malaria are under development, with no completely effective vaccine yet available. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunizing mice with live, radiation-
attenuatedThe attenuator plays an important regulatory role in prokaryotic cells because of the absence of the nucleus in prokaryotic organisms. The attenuator refers to a specific regulatory sequence that, when transcribed into RNA, forms hairpin structures to stop translation when certain conditions are...
sporozoiteIn the life-cycle of apicomplexan protozoa, sporozoites are cells that infect new hosts. In the parasites that cause malaria , for instance, the sporozoites are cells that develop in the mosquito's salivary glands, leave the mosquito during a blood meal, and enter the liver where they multiply...
s, providing protection to about 60% of the mice upon subsequent injection with normal, viable sporozoites. Since the 1970s, there has been a considerable effort to develop similar vaccination strategies within humans. It was determined that an individual can be protected from a
P. falciparum infection if they receive over 1,000 bites from infected, irradiated mosquitoes.
It has been generally accepted that it is impractical to provide at-risk individuals with this vaccination strategy, but that has been recently challenged with work being done by Dr. Stephen Hoffman, one of the key researchers who originally sequenced the genome of
Plasmodium falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
. His work most recently has revolved around solving the logistical problem of isolating and preparing the parasites equivalent to 1000 irradiated mosquitoes for mass storage and inoculation of human beings. The company has recently received several multi-million dollar grants from the
Bill & Melinda Gates FoundationThe Bill & Melinda Gates Foundation is the largest transparently operated private foundation in the world, founded by Bill and Melinda Gates. The foundation is "driven by the interests and passions of the Gates family"...
and the U.S. government to begin early clinical studies in 2007 and 2008. The Seattle Biomedical Research Institute (SBRI), funded by the Malaria Vaccine Initiative, assures potential volunteers that "the [2009] clinical trials won't be a life-threatening experience. While many volunteers [in Seattle] will actually contract malaria, the cloned strain used in the experiments can be quickly cured, and does not cause a recurring form of the disease." "Some participants will get experimental drugs or vaccines, while others will get placebo."
Instead, much work has been performed to try and understand the
immunologicalAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumour cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
processes that provide protection after immunization with irradiated sporozoites. After the mouse vaccination study in 1967, it was hypothesized that the injected sporozoites themselves were being recognized by the immune system, which was in turn creating
antibodiesAntibodies are gamma globulin proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses...
against the parasite. It was determined that the immune system was creating antibodies against the circumsporozoite protein (CSP) which coated the sporozoite. Moreover, antibodies against CSP prevented the sporozoite from invading hepatocytes. CSP was therefore chosen as the most promising protein on which to develop a vaccine against the malaria sporozoite. It is for these historical reasons that vaccines based on CSP are the most numerous of all malaria vaccines.
Presently, there is a huge variety of vaccine candidates on the table. Pre-erythrocytic vaccines (vaccines that target the parasite before it reaches the blood), in particular vaccines based on CSP, make up the largest group of research for the malaria vaccine. Other vaccine candidates include: those that seek to induce immunity to the blood stages of the infection; those that seek to avoid more severe pathologies of malaria by preventing adherence of the parasite to blood venules and
placentaThe placenta is an organ unique to mammals that connects the developing fetus to the uterine wall. The placenta supplies the fetus with oxygen and food, and allows fetal waste to be disposed of via the maternal kidneys...
; and
transmissionIn medicine, transmission is the passing of a disease from an infected individual or group to a previously uninfected individual or group.The microorganisms that cause disease may be transmitted from one person to another by one or more of the following means:* droplet contact - coughing or...
-blocking vaccines that would stop the development of the parasite in the mosquito right after the mosquito has taken a bloodmeal from an infected person. It is hoped that the sequencing of the
P. falciparum genomeIn modern molecular biology the genome refers to all of its hereditary information encoded in DNA .The genome includes both the genes and the non-coding sequences of the DNA. The term was adapted in 1920 by Hans Winkler, Professor of Botany at the University of Hamburg, Germany...
will provide targets for new drugs or vaccines.
The first vaccine developed that has undergone field trials, is the SPf66, developed by
Manuel Elkin PatarroyoManuel Elkin Patarroyo is a Colombian pathologist who developed the world's first synthetic vaccine for malaria, a disease transmitted by mosquitoes that affects millions of people in tropical and subtropical regions, including parts of the Americas, Asia, and Africa...
in 1987. It presents a combination of antigens from the sporozoite (using CS repeats) and merozoite parasites. During phase I trials a 75% efficacy rate was demonstrated and the vaccine appeared to be well tolerated by subjects and immunogenic. The phase IIb and III trials were less promising, with the efficacy falling to between 38.8% and 60.2%. A trial was carried out in Tanzania in 1993 demonstrating the efficacy to be 31% after a years follow up, however the most recent (though controversial) study in The Gambia did not show any effect. Despite the relatively long trial periods and the number of studies carried out, it is still not known how the SPf66 vaccine confers immunity; it therefore remains an unlikely solution to malaria.
The CSP was the next vaccine developed that initially appeared promising enough to undergo trials. It is also based on the circumsporoziote protein, but additionally has the recombinant (Asn-Ala-Pro15Asn-Val-Asp-Pro)2-Leu-Arg(R32LR) protein covalently bound to a purified
Pseudomonas aeruginosaPseudomonas aeruginosa is a common bacterium which can cause disease in animals and humans. It is found in soil, water, skin flora and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also with little oxygen, and has thus colonised many natural and...
toxin (A9). However at an early stage a complete lack of protective immunity was demonstrated in those inoculated. The study group used in Kenya had an 82% incidence of parasitaemia whilst the control group only had an 89% incidence. The vaccine intended to cause an increased T-lymphocyte response in those exposed, this was also not observed.
The efficacy of Patarroyo's vaccine has been disputed with some US scientists concluding in
The LancetThe Lancet is a peer-reviewed general medical journal, published weekly.One of the world's best-known and most respected general medical journals, with editorial offices in London and New York, The Lancet was founded in 1823 by Thomas Wakley, who named it after the surgical instrument called a...
(1997) that "the vaccine was not effective and should be dropped" while the Colombian accused them of "arrogance" putting down their assertions to the fact that he came from a developing country.
The RTS,S/AS02A vaccine is the candidate furthest along in vaccine trials. It is being developed by a partnership between the PATH Malaria Vaccine Initiative (a grantee of the Gates Foundation), the
pharmaceutical companyThe pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies can deal in generic and/or brand medications. They are subject to a variety of laws and regulations regarding the patenting, testing and marketing of drugs.-History:The...
,
GlaxoSmithKline GlaxoSmithKline plc is a United Kingdom-based pharmaceutical, biological, and healthcare company. GSK is the world's second largest pharmaceutical company and a research-based company with a wide portfolio of pharmaceutical products covering anti-infectives, central nervous system, respiratory,...
, and the Walter Reed Army Institute of Research In the vaccine, a portion of CSP has been fused to the
immunogenicImmunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response.- Immunogenicity :The ability to induce humoral and/or cell-mediated immune responses....
"S
antigenAn antigen is a substance that prompts the generation of antibodies and can cause an immune response. "Self" antigens are usually tolerated by the immune system; whereas "Non-self" antigens are identified as intruders and attacked by the immune system...
" of the hepatitis B virus; this
recombinantRecombinant may refer to :* A recombinant organism - an organism that contains a different combination of alleles from either of its parents. See Recombination.* Recombinant DNA - a form of artificial DNA...
protein is injected alongside the potent AS02A
adjuvantAdjuvants are pharmacological or immunological agents that modify the effect of other agents while having few if any direct effects when given by themselves...
. In October 2004, the RTS,S/AS02A researchers announced results of a
Phase IIb trialClinical trials are conducted to allow safety and efficacy data to be collected for new drugs or devices. These trials can only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and Health Authority/Ethics Committee approval is...
, indicating the vaccine reduced infection risk by approximately 30% and severity of infection by over 50%. The study looked at over 2,000
MozambicanMozambique, officially the Republic of Mozambique , is a country in southeastern Africa bordered by the Indian Ocean to the east, Tanzania to the north, Malawi and Zambia to the northwest, Zimbabwe to the west and Swaziland and South Africa to the southwest. It was explored by Vasco da Gama in 1498...
children. More recent testing of the RTS,S/AS02A vaccine has focused on the safety and efficacy of administering it earlier in infancy: In October 2007, the researchers announced results of a
phase I/IIb trialClinical trials are conducted to allow safety and efficacy data to be collected for new drugs or devices. These trials can only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and Health Authority/Ethics Committee approval is...
conducted on 214 Mozambican infants between the ages of 10 and 18 months in which the full three-dose course of the vaccine led to a 62% reduction of infection with no serious side-effects save some pain at the point of injection. Further research will delay this vaccine from commercial release until around 2011.
Other methods
Education in recognizing the symptoms of malaria has reduced the number of cases in some areas of the developing world by as much as 20%. Recognizing the disease in the early stages can also stop the disease from becoming a killer. Education can also inform people to cover over areas of stagnant, still water e.g. Water Tanks which are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people. This is most put in practice in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas.
The
Malaria Control ProjectMalaria Control Project is an application that makes use of network computing for stochastic modelling of the clinical epidemiology and natural history of Plasmodium falciparum malaria- Computing platform :...
is currently using downtime computing power donated by individual volunteers around the world (see
Volunteer computingVolunteer computing is a type of distributed computing in which computer owners donate their computing resources to one or more "projects".-History:...
and BOINC) to simulate models of the health effects and transmission dynamics in order to find the best method or combination of methods for malaria control. This modeling is extremely computer intensive due to the simulations of large human populations with a vast range of parameters related to biological and social factors that influence the spread of the disease. It is expected to take a few months using volunteered computing power compared to the 40 years it would have taken with the current resources available to the scientists who developed the program.
An example of the importance of computer modeling in planning malaria
eradicationEradication is the reduction of an infectious disease's prevalence in the global human or animal host population to zero. A number of world organizations together with local governments are working to fully eradicate various diseases...
programs is shown in the paper by Águas and others. They showed that eradication of malaria is crucially dependent on finding and treating the large number of people in endemic areas with asymptomatic malaria, who act as a reservoir for infection. The malaria parasites do not affect animal species and therefore eradication of the disease from the human population would be expected to be effective.
Other interventions for the control of malaria include
mass drug administrationThe administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration . This article describes the administration of antimalarial drugs to whole populations an intervention which has been used as a malaria-control measure for more than 70 years...
s and
intermittent preventive therapyIntermittent preventive therapy is a public health intervention aimed at treating and preventing malaria episodes in infants , children , schoolchildren and pregnant women...
.
Treatment
Active malaria infection with
P. falciparum is a
medical emergencyA medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...
requiring
hospitalA hospital is an institution for health care providing patient treatment by specialized staff and equipment, and often but not always providing for longer-term patient stays....
ization. Infection with
P. vivax,
P. ovale or
P. malariae can often be treated on an outpatient basis. Treatment of malaria involves supportive measures as well as specific antimalarial drugs. When properly treated, someone with malaria can expect a complete recovery.
Antimalarial drugs
{{further|
Antimalarial drugAntimalarial drugs are designed to prevent or cure malaria. Some antimalarial agents, particularly chloroquine and hydroxychloroquine, are also used in the treatment of rheumatoid arthritis and lupus associated arthritis. There are many of these drugs currently on the market...
s}}
There are several families of drugs used to treat malaria.
ChloroquineChloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-Uses:* It has long been used in the treatment or prevention of malaria. After the malaria parasite Plasmodium falciparum started to develop widespread resistance to chloroquine, new potential utilisations of...
is very cheap and, until recently, was very effective, which made it the antimalarial drug of choice for many years in most parts of the world. However, resistance of
Plasmodium falciparum to chloroquine has spread recently from Asia to Africa, making the drug ineffective against the most dangerous Plasmodium strain in many affected regions of the world. In those areas where chloroquine is still effective it remains the first choice. Unfortunately, chloroquine-resistance is associated with reduced sensitivity to other drugs such as
quinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine....
and
amodiaquineAmodiaquine is a 4-aminoquinoline compound related to chloroquine, used as an antimalarial and anti-inflammatory agent....
.
There are several other substances that are used for treatment and, partially, for prevention (prophylaxis). Many drugs may be used for both purposes; larger doses are used to treat cases of malaria. Their deployment depends mainly on the frequency of resistant parasites in the area where the drug is used. One drug {{As of|2007|alt=currently}} being investigated for possible use as an anti-malarial, especially for treatment of drug-resistant strains, is the
beta blockerBeta blockers is a class of drugs used for various indications, but particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction , and hypertension. Propranolol was the first clinically useful beta adrenergic receptor antagonist. Invented by Sir James W...
propranololPropranolol is a non-selective beta blocker mainly used in the treatment of hypertension. It was the first successful beta blocker developed. It is the only drug proven effective for the prophylaxis of migraines in children...
. Propranolol has been shown to block both
Plasmodiums ability to enter red blood cell and establish an infection, as well as parasite replication. A December 2006 study by Northwestern University{{Infobox university|name = Northwestern University|image_name = NU seal.png|motto = Quaecumque sunt vera |mottoeng =Whatsoever things are true |established = 1851|type = Private|calendar = Quarter...
researchers suggested that propranolol may reduce the dosages required for existing drugs to be effective against P. falciparum
by 5- to 10-fold, suggesting a role in combination therapies.
Currently available anti-malarial drugs include:
- Artemether
Artemether is an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria. It is combined with Lumefantrine and sold by Novartis under the brand names Riamet and Co-Artem.It is an ether derivative of artemisinin....
-lumefantrineLumefantrine is an antimalarial drug.The term "co-artemether" is sometimes used to describe the administration of lumefantrine with artemether....
(Therapy only, commercial names
CoartemCoartem is an artemisinin-based combination therapy indicated for the treatment of acute uncomplicated plasmodium falciparum malaria, the most dangerous form of the disease...
and Riamet)
ArtesunateArtesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
-amodiaquineAmodiaquine is a 4-aminoquinoline compound related to chloroquine, used as an antimalarial and anti-inflammatory agent....
(Therapy only)
ArtesunateArtesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
-mefloquineMefloquine is an orally-administered antimalarial drug used as a prophylaxis against and treatment for malaria. It also goes by the trade name Lariam or Mefaquin and chemical name mefloquine hydrochloride . Mefloquine was developed in the 1970s at the Walter Reed Army Institute of Research in the...
(Therapy only)
ArtesunateArtesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
-SulfadoxineThere are several sulfonamide-based groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...
/pyrimethaminePyrimethamine is a medication used for protozoal infections. It is commonly used as an antimalarial drug , and is also used in the treatment of Toxoplasma gondii infections in immunocompromised patients, such as HIV-positive individuals.-Mechanism of action:Pyrimethamine interferes with...
(Therapy only)
AtovaquoneAtovaquone is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about US$2.13 per standard 250 mg. tablet...
-proguanilProguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
, trade name Malarone (Therapy and prophylaxis)
QuinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine....
(Therapy only)
ChloroquineChloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-Uses:* It has long been used in the treatment or prevention of malaria. After the malaria parasite Plasmodium falciparum started to develop widespread resistance to chloroquine, new potential utilisations of...
(Therapy and prophylaxis; usefulness now reduced due to resistance)
CotrifazidCotrifazid is a treatment and prophylaxis for malaria consisting of a multiple complex combination of rifampicin, isoniazid, sulfamethoxazole, and trimethoprim....
(Therapy and prophylaxis)
DoxycyclineDoxycycline is a member of the tetracycline antibiotics group and is commonly used to treat a variety of infections. Doxycycline is a semi-synthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin received...
(Therapy and prophylaxis)
MefloquineMefloquine is an orally-administered antimalarial drug used as a prophylaxis against and treatment for malaria. It also goes by the trade name Lariam or Mefaquin and chemical name mefloquine hydrochloride . Mefloquine was developed in the 1970s at the Walter Reed Army Institute of Research in the...
, trade name Lariam (Therapy and prophylaxis)
PrimaquinePrimaquine is a medication used in the treatment of malaria and Pneumocystis pneumonia. It is a member of the 8-aminoquinoline group of drugs that includes tafenoquine and pamaquine.-Radical cure:...
(Therapy in P. vivax and P. ovale only; not for prophylaxis)
ProguanilProguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
(Prophylaxis only)
SulfadoxineThere are several sulfonamide-based groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...
-pyrimethaminePyrimethamine is a medication used for protozoal infections. It is commonly used as an antimalarial drug , and is also used in the treatment of Toxoplasma gondii infections in immunocompromised patients, such as HIV-positive individuals.-Mechanism of action:Pyrimethamine interferes with...
(Therapy; prophylaxis for semi-immune pregnant women in endemic countries as "Intermittent Preventive Treatment" - IPT)
HydroxychloroquineHydroxychloroquine is an antimalarial drug, sold under the trade name Plaquenil, also used to reduce inflammation in the treatment of Rheumatoid arthritis and lupus.-Classification and use:...
, trade name Plaquenil (Therapy and prophylaxis)
The development of drugs was facilitated when Plasmodium falciparum
was successfully culturedMalaria culture is the method to grow malaria parasites continuously in an in vitro environment.Plasmodium falciparum is currently the only human malaria parasite that has been successfully cultured in vitro...
. This allowed in vitro testing of new drug candidates.
Extracts of the plant Artemisia annuaArtemisia annua, also known as Sweet Wormwood, Sweet Annie, Sweet Sagewort or Annual Wormwood , is a common type of wormwood that is native to temperate Asia, but naturalized throughout the world.-Characteristics:...
, containing the compound
artemisininArtemisinin is a drug used to treat multi-drug resistant strains of falciparum malaria. The compound is isolated from the plant Artemisia annua. Not all plants of this species contain artemisinin. Apparently it is only produced when the plant is subjected to certain conditions, most likely biotic...
or semi-synthetic derivatives (a substance unrelated to quinine), offer over 90% efficacy rates, but their supply is not meeting demand. One study in Rwanda showed that children with uncomplicated P. falciparum malaria demonstrated fewer clinical and parasitological failures on post-treatment day 28 when amodiaquine was combined with
artesunateArtesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
, rather than administered alone (OR = 0.34). However, increased resistance to amodiaquine during this study period was also noted.
Since 2001 the
World Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health...
has recommended using
artemisininArtemisinin is a drug used to treat multi-drug resistant strains of falciparum malaria. The compound is isolated from the plant Artemisia annua. Not all plants of this species contain artemisinin. Apparently it is only produced when the plant is subjected to certain conditions, most likely biotic...
-based combination therapy (ACT) as first-line treatment for uncomplicated malaria in areas experiencing resistance to older medications. The most recent
WHO*Who is an English language interrogative pronoun.-In fiction:*Who? , a 1958 novel by science fiction author Algis Budrys, turned into a film with the same title in 1973*Doctor Who, a British science fiction television series...
treatment guidelines for malaria recommend four different ACTs. While numerous countries, including most African nations, have adopted the change in their official malaria treatment policies, cost remains a major barrier to ACT implementation. Because ACTs cost up to twenty times as much as older medications, they remain unaffordable in many malaria-endemic countries. The molecular target of artemisinin is controversial, although recent studies suggest that
SERCASERCA, or Sarco/Endoplasmic Reticulum Ca2+-ATPase, is a calcium ATPase type P-ATPase.-Function:SERCA resides in the sarcoplasmic reticulum within muscle cells...
, a calcium pump in the
endoplasmic reticulumThe endoplasmic reticulum is an eukaryotic organelle that forms an interconnected network of tubules, vesicles, and cisternae within cells. The lacey membranes of the endoplasmic reticulum were first seen by Keith R. Porter, Albert Claude, and Ernest F...
may be associated with artemisinin resistance. Malaria parasites can develop resistance to artemisinin and resistance can be produced by mutation of SERCA. However, other studies suggest the mitochondrion is the major target for artemisinin and its analogs.
Although effective anti-malarial drugs are on the market, the disease remains a threat to people living in endemic areas who have no proper and prompt access to effective drugs. Access to pharmacies and health facilities, as well as drug costs, are major obstacles.
Médecins Sans FrontièresMédecins Sans Frontières , or Doctors Without Borders, is a secular humanitarian-aid non-governmental organization best known for its projects in war-torn regions and developing countries facing endemic disease....
estimates that the cost of treating a malaria-infected person in an endemic country was between $0.25 and $2.40 per dose in 2002.
Counterfeit drugs
Sophisticated counterfeits have been found in several Asian countries such as
CambodiaThe Kingdom of Cambodia , formerly known as Kampuchea , is a country in South East Asia with a population of over 14 million people. The kingdom's capital and largest city is Phnom Penh...
,
ChinaChina is a cultural region, an ancient civilization, and, depending on perspective, a national or multinational entity extending over a large area in East Asia....
,
IndonesiaThe Republic of Indonesia is a country in Southeast Asia and Oceania. Indonesia comprises 17,508 islands. With an estimated population of around 237 million people, it is the world's fourth most populous country, with the world's largest population of Muslims.Indonesia is a republic, with an...
,
LaosLaos , officially the Lao People's Democratic Republic, is the only landlocked country in Southeast Asia, bordered by Burma and People's Republic of China to the northwest, Vietnam to the east, Cambodia to the south and Thailand to the west...
,
ThailandThe Kingdom of Thailand is an independent country that lies in the heart of Southeast Asia.It is bordered to the north by Laos and Burma, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the west by the Andaman Sea and Burma...
,
VietnamVietnam , officially the Socialist Republic of Vietnam , is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea to the east...
and are an important cause of avoidable death in those countries.
WHO*Who is an English language interrogative pronoun.-In fiction:*Who? , a 1958 novel by science fiction author Algis Budrys, turned into a film with the same title in 1973*Doctor Who, a British science fiction television series...
have said that studies indicate that up to 40% of
artesunateArtesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
based malaria medications are counterfeit, especially in the Greater
MekongThe Mekong River is one of the world’s major rivers. It is the world's 10th-longest river and the 7th-longest in Asia. . Its estimated length is , and it drains an area of ....
region and have established a rapid alert system to enable information about counterfeit drugs to be rapidly reported to the 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.
History
{{further|
History of malariaThe history of malaria predates humanity, as this ancient disease evolved before humans did. Malaria, a widespread and potentially lethal infectious disease, has afflicted people for much of human history, and has affected settlement patterns...
}}
Malaria has infected humans for over 50,000 years, and Plasmodium
may have been a human pathogenA pathogen , infectious agent, or germ, is a biological agent that causes disease or illness to its host....
for the entire history of the species. Close relatives of the human malaria parasites remain common in chimpanzees. References to the unique periodic fevers of malaria are found throughout recorded history, beginning in 2700 BC in China. The term malaria originates from MedievalThe Middle Ages of European history is a period of European history covering roughly a millennium in the 5th century through 16th centuries. More specific starting and ending points are sometimes adopted by scholars to suit their respective specializations or current focus...
ItalianItalian is a Romance language spoken by about 60 million people in Italy, and by a total of around 70 million in the world. In Switzerland, Italian is one of four official languages. It is also the official language of San Marino, as well as the primary language of Vatican City...
: mala aria—"
bad airThe miasmatic theory of disease held that diseases such as cholera, chlamydia or the Black Death were caused by a miasma , a noxious form of "bad air". This concept has been supplanted by the germ theory of disease....
"; and the disease was formerly called ague
or marsh fever due to its association with swamps and marshland. Malaria was once common in most of
EuropeEurope is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally divided from Asia to its east by the water divide of the Ural Mountains, the Ural River, the Caspian Sea, the Caucasus Mountains , and the Black Sea to the southeast...
and
North AmericaNorth America is the northern continent of the Americas, situated in the Earth's northern hemisphere and in the western hemisphere. It is bordered on the north by the Arctic Ocean, on the east by the North Atlantic Ocean, on the southeast by the Caribbean Sea, and on the west by the North Pacific...
, where it is no longer
endemicIn epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
, though imported cases do occur.
Scientific studies on malaria made their first significant advance in 1880, when a French army doctor working in the military hospital of
ConstantineConstantine is the capital of Constantine Province in north-eastern Algeria. Slightly inland, it is about 80 kilometers from the Mediterranean coast....
in
AlgeriaAlgeria , officially the People's Democratic Republic of Algeria, is a country located in North Africa. It is the largest country on the Mediterranean sea, the second largest on the African continent and the eleventh-largest country in the world in terms of land area.It is bordered by Tunisia in...
named
Charles Louis Alphonse LaveranCharles Louis Alphonse Laveran was a French physician.In 1880, while working in the military hospital in Constantine, Algeria, he discovered that the cause of malaria is a protozoan, after observing the parasites in a blood smear taken from a patient who had just died of malaria...
observed parasites for the first time, inside the
red blood cellRed blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood. They take up oxygen in the lungs or gills and release it while squeezing through the body's capillaries. The cells are filled with hemoglobin, a...
s of people suffering from malaria. He, therefore, proposed that malaria is caused by this organism, the first time a protist was identified as causing disease. For this and later discoveries, he was awarded the 1907 Nobel Prize for Physiology or Medicine. The malarial parasite was called Plasmodium by the Italian scientists
Ettore MarchiafavaEttore Marchiafava was an Italian physician and zoologist who worked on malariaEttore Marchiafava , was the personal doctor of three popes and the Royal House of Savoy, a senator and professor of Pathological Anatomy at the Sapienza University of Rome...
and
Angelo CelliAngelo Celli was an Italian physician and zoologist who studied malaria.Celli graduated in medicine in 1878 at the Sapienza University of Rome, where he became hygiene professor. In 1880 with Ettore Marchiafava he studied a new protozoan discovered by Alphonse Laveran and which they called...
. A year later,
Carlos FinlayCarlos Juan Finlay was a Cuban physician and scientist, recognized as a pioneer in yellow fever research.- Early life and education :...
, a Cuban doctor treating patients with
yellow feverYellow fever is an acute viral disease. The virus, a 40 to 50 nm enveloped RNA virus of the family of Flaviviridae is transmitted by the bite of mosquitoes...
in
HavanaHavana is the capital city, major port, and leading commercial centre of Cuba. The city is one of the 14 Cuban provinces. The city/province has 2.4 million inhabitants, and the urban area over 3.7 million, making Havana the largest city in both Cuba and the Caribbean region...
, provided strong evidence that mosquitoes were transmitting disease to and from humans. This work followed earlier suggestions by
Josiah C. NottJosiah Clark Nott was an American physician and surgeon. He was also acal]], yellow fever, and race theories.-Biography:Josiah Nott was born in South Carolina, son of the Federalist politician and judge Abraham Nott. He received his medical degree from the University of Pennsylvania in 1827 and...
, and work by
Patrick MansonSir Patrick Manson was a Scottish physician who made important discoveries in parasitology and was the founder of the tropical medicine field....
on the transmission of
filariasisFilariasis is a parasitic and infectious tropical disease, that is caused by thread-like filarial nematode worms in the superfamily Filarioidea, also known as "filariae". There are 9 known filarial nematodes which use humans as the definitive host...
.
However, it was Britain's
Sir Ronald RossSir Ronald Ross KCB was a British physician.-Early life:Ross was born in Almora, India. He was the eldest son of General Sir Campbell Claye Grant Ross of the Indian Army and Matilda Charlotte Elderton. His grandfather was Lieutenant Colonel Hugh Ross.At the age of eight, Ross was sent to England...
working in the Presidency General Hospital in
Calcutta, formerly , is the capital of the Indian state of West Bengal. It is located in eastern India on the east bank of the River Hooghly. When referred to as Calcutta, it usually includes the suburbs, and thus its population exceeds 15 million, making it India's third-largest metropolitan area and...
who finally proved in 1898 that malaria is transmitted by mosquitoes. He did this by showing that certain mosquito species transmit malaria to birds and isolating malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. For this work Ross received the 1902 Nobel Prize in Medicine. After resigning from the Indian Medical Service, Ross worked at the newly-established
Liverpool School of Tropical MedicineThe Liverpool School of Tropical Medicine , England, was founded on 12 November 1898, by a donation from Sir Alfred Lewis Jones, a Liverpool Shipowner...
and directed malaria-control efforts in
EgyptEgypt , officially the Arab Republic of Egypt, is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Western Asia...
,
PanamaPanama, officially the Republic of Panama , is the southernmost country of both Central America and, in turn, North America. Situated on the isthmus connecting North and South America, it is bordered by Costa Rica to the northwest, Colombia to the southeast, the Caribbean Sea to the north and the...
,
GreeceGreece , officially the Hellenic Republic , is a country in southeastern Europe, situated on the southern end of the Balkan Peninsula....
and
MauritiusMauritius , officially the Republic of Mauritius, is an island nation off the coast of the African continent in the southwest Indian Ocean, about east of Madagascar. In addition to the island of Mauritius, the Republic includes the islands of Cargados Carajos, Rodrigues and the Agalega Islands...
. The findings of Finlay and Ross were later confirmed by a medical board headed by
Walter ReedMajor Walter Reed, M.D., was a U.S. Army physician who in 1900 led the team which postulated and confirmed the theory that yellow fever is transmitted by mosquitoes, rather than by direct contact...
in 1900, and its recommendations implemented by
William C. GorgasWilliam Crawford Gorgas KCMG was a United States physician and 22nd Surgeon General of the U.S. Army...
in
the health measures undertakenOne of the greatest challenges facing the builders of the Panama Canal was dealing with the tropical diseases rife in the area. The health measures taken during the construction contributed greatly to the success of the canal's construction...
during construction of the
Panama CanalThe Panama Canal is a ship canal which joins the Caribbean Sea to the Pacific ocean. One of the largest and most difficult engineering projects ever undertaken, it had an enormous impact on shipping between the two oceans, replacing the long and treacherous route via the Drake Passage and Cape Horn...
. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against this disease.
The first effective treatment for malaria came from the bark of
cinchona treeCinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cm long. The flowers are white, pink or red,...
, which contains
quinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine....
. This tree grows on the slopes of the
AndesThe Andes are the world's longest exposed mountain range. They lie as a continuous chain of highland along the western coast of South America...
, mainly in
PeruPeru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean.Peruvian territory was home to the Norte Chico...
. A tincture made of this natural product was used by the inhabitants of
PeruPeru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean.Peruvian territory was home to the Norte Chico...
to control malaria, and the Jesuits introduced this practice to Europe during the 1640s, where it was rapidly accepted. However, it was not until 1820 that the active ingredient, quinine, was extracted from the bark, isolated and named by the French chemists
Pierre Joseph PelletierPierre-Joseph Pelletier was a French chemist who did notable research on vegetable alkaloids, and was the co-discoverer of quinine and strychnine....
and
Joseph Bienaimé CaventouJoseph Bienaimé Caventou was a French chemist.He was a professor at the École de Pharmacie in Paris. He collaborated with Pierre-Joseph Pelletier in a Parisian laboratory located behind an apothecary. He was a pioneer in the use of mild solvents to isolate a number of active ingredients from...
.
In the early 20th century, before antibiotics, patients with
syphilisSyphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum subspecies pallidum. The route of transmission of syphilis is almost always through sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero.The...
were intentionally infected with malaria to create a
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
, following the work of
Julius Wagner-JaureggJulius Wagner-Jauregg, was an Austrian physician.He studied Medicine at the University of Vienna from 1874 to 1880, where he also studied with Salomon Stricker in the Institute of General and Experimental Pathology, obtaining his doctor's degree in 1880...
. By accurately controlling the fever with
quinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine....
, the effects of both syphilis and malaria could be minimized. Although some patients died from malaria, this was preferable to the almost-certain death from syphilis.
Although the blood stage and mosquito stages of the malaria life cycle were identified in the 19th and early 20th centuries, it was not until the 1980s that the latent liver form of the parasite was observed. The discovery of this latent form of the parasite finally explained why people could appear to be cured of malaria but still relapse years after the parasite had disappeared from their bloodstreams.
Evolutionary pressure of malaria on human genes
{{further|
EvolutionIn biology, evolution is change in the genetic material of a population of organisms from one generation to the next. Though changes produced in any one generation are normally small, differences accumulate with each generation and can, over time, cause substantial changes in the population, a...
,
Natural selectionNatural selection is the process by which heritable traits that make it more likely for an organism to survive and successfully reproduce become more common in a population over successive generations...
}}
Malaria is thought to have been the greatest
selective pressureIn the context of evolution, certain traits or alleles of a species may be subject to selection. Under selection, individuals with advantageous or "adaptive" traits tend to be more successful than their peers reproductively—meaning they contribute more offspring to the succeeding generation than...
on the
human genomeThe human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs. Twenty-two of these are autosomal chromosome pairs, while the remaining pair is sex-determining...
in recent history. This is due to the high levels of
mortalityDeath is the termination of the biological functions that define a living organism. It refers to both a particular event and to the condition that results thereby. The true nature of the latter has for millennia been a central concern of the world's religious traditions and of philosophical...
and morbidity caused by malaria, especially the
P. falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
species.
Sickle-cell disease
{{Original research|date=April 2009}}
{{Unreferenced section|date=April 2009}}
The most-studied influence of the malaria parasite upon the human genome is a hereditary blood disease,
sickle-cell diseaseSickle-cell disease, or sickle-cell anaemia , is a life-long blood disorder characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various complications. The sickling occurs because of a mutation in the...
. The sickle-cell trait causes disease, but even those only partially affected by sickle-cell have substantial protection against malaria.
In sickle-cell disease, there is a mutation in the HBB gene, which encodes the beta-globin subunit of haemoglobin. The normal allele encodes a glutamate at position six of the beta-globin protein, whereas the sickle-cell allele encodes a
valineValine is an α-amino acid with the chemical formula HO
2CCHCH
2.
L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
. This change from a hydrophilic to a hydrophobic amino acid encourages binding between haemoglobin molecules, with polymerization of haemoglobin deforming red blood cells into a "sickle" shape. Such deformed cells are cleared rapidly from the blood, mainly in the spleen, for destruction and recycling.
In the merozoite stage of its life cycle, the malaria parasite lives inside red blood cells, and its metabolism changes the internal chemistry of the red blood cell. Infected cells normally survive until the parasite reproduces, but, if the red cell contains a mixture of sickle and normal haemoglobin, it is likely to become deformed and be destroyed before the daughter parasites emerge. Thus, individuals heterozygous for the mutated allele, known as sickle-cell trait, may have a low and usually-unimportant level of anaemia, but also have a greatly reduced chance of serious malaria infection. This is a classic example of
heterozygote advantageA heterozygote advantage describes the case in which the heterozygote genotype has a higher relative fitness than either the homozygote dominant or homozygote recessive genotype. This selection favoring the heterozygote is one of the mechanisms that maintain polymorphism and help to explain some...
.
Individuals homozygous for the mutation have full sickle-cell disease and in traditional societies rarely live beyond adolescence. However, in populations where malaria is
endemicIn epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
, the frequency of sickle-cell genes is around 10%. The existence of four
haplotypeThe term haplotype is a contraction of the term 'haploid genotype'. In genetics, a haplotype is a combination of alleles at multiple loci that are transmitted together on the same chromosome...
s of sickle-type hemoglobin suggests that this mutation has emerged
independentlyConvergent evolution describes the acquisition of the same biological trait in unrelated lineages.The wing is a classic example of convergent evolution in action. Although their last common ancestor did not have wings, birds and bats do, and are capable of powered flight. The wings are similar in...
at least four times in malaria-endemic areas, further demonstrating its evolutionary advantage in such affected regions. There are also other mutations of the HBB gene that produce haemoglobin molecules capable of conferring similar resistance to malaria infection. These mutations produce haemoglobin types HbE and HbC, which are common in
Southeast AsiaManila
Bangkok
Ho Chi Minh City
Kuala Lumpur
Singapore
Yangon
Bandung
Hanoi
Surabaya
Taichung
Kaohsiung
Medan|-|}...
and Western Africa, respectively.
Thalassaemias
Another well-documented set of mutations found in the human genome associated with malaria are those involved in causing blood disorders known as thalassaemias. Studies in
SardiniaSardinia is the second-largest island in the Mediterranean Sea . The area of Sardinia is . The nearest land masses to the island are the French island of Corsica, the Italian Peninsula, Tunisia, and the Spanish Balearic Islands...
and
Papua New GuineaPapua New Guinea , officially the Independent State of Papua New Guinea, is a country in Oceania, occupying the eastern half of the island of New Guinea and numerous offshore islands...
have found that the gene frequency of β-thalassaemias is related to the level of malarial endemicity in a given population. A study on more than 500 children in
LiberiaLiberia , officially the Republic of Liberia, is a country on the west coast of Africa, bordered by Sierra Leone, Guinea, Côte d'Ivoire, and the Atlantic Ocean. As of the 2008 Census, the nation is home to 3,476,608 people and covers ....
found that those with β-thalassaemia had a 50% decreased chance of getting clinical malaria. Similar studies have found links between gene frequency and malaria endemicity in the α+ form of α-thalassaemia. Presumably these genes have also been
selectedNatural selection is the process by which heritable traits that make it more likely for an organism to survive and successfully reproduce become more common in a population over successive generations...
in the course of human evolution.
Duffy antigens
The
Duffy antigenThe Duffy antigen