Malaria is a mosquito-borne infectious disease caused by a eukaryotic protist related to the genus Plasmodium . It is widespread in both tropical and sub-tropical regions – including the Americas, Asia, and Africa. Each year, there are approximately 350 – 500 million cases of malaria, killing between one and three million people. The majority of these deaths are young children in sub-Saharan Africa1 . It’s estimated that ninety percent (90%) of the deaths from Malaria occur in sub-Saharan Africa. Malaria is commonly associated with poverty, however, it is also a cause of poverty and a major hindrance to economic development.
F ive (5) species of the plasmodium parasite can infect humans; the most serious forms of the disease are caused by Plasmodium falciparum . Malaria caused by Plasmodium vivax , Plasmodium ovale , and Plasmodium malariae cause a milder strain of the disease that is not generally fatal. A fifth species, Plasmodium knowlesi , is a zoonosis that causes malaria in macaques but can also infect humans2 .
Malaria is usually transmitted by the bite of a female Anopheles mosquito. When a mosquito bites an infected person, a small amount of blood is taken, which contains the Malaria parasites. These develop within the mosquito and, about one (1) week later, when the mosquito takes its next blood meal, the parasites are injected with the mosquito’s saliva into the person being bitten. Following a period of between two (2) weeks and several months (or occasionally years) spent in the liver, the parasites begin to multiply within the red blood cells resulting in symptoms that include fever and headache.
A wide variety of anti-malarial drugs are available to treat malaria. In the last five (5) years, treatment of P. falciparum infections in endemic countries has been transformed by the use of combinations of drugs containing an artemisinin derivative. Severe cases of malaria is treated with intravenous (IV) or intramuscular (IM) quinine or, increasingly, the artemisinin derivative artesunate . Several drugs are also available to prevent malaria in travelers to malaria-endemic countries (prophylaxis). Unfortunately, resistance has developed to several anti-malarial drugs – most notably chloroquine .
Malaria transmission can be reduced by the prevention of mosquito bites by distribution or inexpensive mosquito nets and insect repellant, or by mosquito-control measures such as spraying insecticides inside houses and/or draining standing water where mosquitoes lay their eggs.
Although many (drugs) are under development, the challenge of producing a widely available vaccine that provide a high level of protection for a sustained period of time is still to be met.
What are the signs and symptoms of malaria?
Symptoms of malaria include fever, shivering / chills, arthralgia3 , vomiting, anemia (caused by hemolysis), hemoglobinuria, retinal damage, and convulsions. Classic symptoms of malaria is cyclical occurrence of sudden coldness followed by rigor and then fever and sweating lasting four (4) to six (6) hours. In malaria caused by P. vivax and P. ovale , this cycle occurs every two (2) days: in P. falciparum , recurrent fever occurs every 36 – 48 hours or it can be a less pronounced, but constant fever. For reasons not yet completely understood, but possibly related to increased intracranial pressure, children with malaria frequently exhibit abnormal posturing – a sign that is usually associated with brain damage4 . In addition, it has been found to cause cognitive impairment – especially in children. It also causes widespread anemia during a period of rapid brain development as well as direct brain damage. The neurological from cerebral malaria of which children are more susceptible.
Severe malaria is almost exclusively caused by P. falciparum infection, and usually arises six (6) to fourteen (14) days after infection. Consequences of severe malaria Splenomegaly (enlarged spleen), severe headache, cerebral ischemia, hepatomegaly (enlarged liver), hypoglycemia, and hemoglobinuria with renal failure may occur. Renal failure may cause black water fever, where hemoglobin from lysed red blood cells leaks into the urine. Severe malaria progresses rapidly and can result in death within hours or days.
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.
What causes malaria?
Malaria parasites
Malaria parasites are members of the genus Plasmodium (phylum Apicomplexa). In humans, malaria is caused by P. falciparum , P. malariae , P. ovale , P. vivax , and P. knowlesi . P. falciparum. P. falciparum is the most common cause of infection and is responsible for about eighty-percent (80%) of all malaria cases. Additionally, it is responsible for about ninety-percent (90%) of the deaths from malaria. Parasitic Plasmodium species also infects 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. braziliamum , P. schwetzi, and P. simium ; however, with the exception of P. knowlesi , these are mostly of limited public health importance.
Mosquito vectors and the Plasmodiumlife cycle
The parasite’s primary (definitive) hosts and transmission vectors are female mosquitoes of the Anopheles genus, while humans and other vertebrates are secondary hosts. Young mosquitoes first ingest the malaria parasite when they feed on an infected human carrier. Once ingested, the parasite gametocytes5 taken up in the blood further differentiate into male or female gametes an then fuse in the mosquito gut. This produces an ookinete that penetrates the gut lining and produces an oocyst in the gut wall. When the oocyst ruptures, it releases sporozites that migrate through the mosquito’s body to the salivary glands, where they are then ready to infect a new human host.
Pathogenesis
Malaria in humans develops via two phases: an exoerythrocytic and an erythrocytic phase. The exoerythrocytic phase involves infection of the hepatic system (the liver), whereas the erythrocytic phase involves infection of the red blood cells. When an infected mosquito pierces a person’s skin to take a blood meal, sporozoites in the mosquito’s saliva enter the bloodstream and migrate to the liver. Within 30 minutes of being introduced into a human host, the sporozites infect hepatocytes, multiplying asexually and asymptomatically for a period of six (6) to fifteen (15) days. Once in the liver, these organisms differentiate to yield thousands of merozoites, which, following the rupture of their host cells, escape into the blood and infect the red blood cells – thus beginning the erythrocytic stage of their life cycle. The parasite escapes the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.
Once inside the red blood cells, the parasites multiply further, and, again, asexually. During this time, they will occasionally break out of their hosts to invade fresh red blood cells. This amplification will occur several times and accounts for the classic description of waves of fever as the simultaneous waves of merozoites escaping and infecting red blood cells.
Some P. vivax and P. ovale sporozites don’t immediately develop into exoerythrocytic-phase merozoites, but rather produce hypnozoites that remain dormant for periods ranging from several months – six (6) to twelve (12) months is typical – to as long as three (3) years. Following a period of dormancy, they re-active and produce merozoites. The Hypnozoites are responsible for long incubation periods and late relapses in these two species of malaria6 .
The parasite is relatively secure from attack by the body’s immune system because, for most of its human life cycle, resides within the liver and blood cells and is invisible to immune surveillance. The one exception to this, however, is when circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. It is this “stickiness” that is the main factor that causes the hemorrhagic complication associated with malaria. High endothelial venules (the smallest branches of the circulatory system) can be blocked by the attachment of the masses of these infected blood cells. The blockage of these vessels causes symptoms such as in placental and cerebral malaria. In cerebral malaria, the sequestered red blood cells can breach the blood brain barrier possibly resulting in 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 sixty (60) variations of the protein within a single parasite and effectively limitless versions within parasite populations. The parasite switches between a broad repertoire of PfEMP1 surface proteins, thus staying one step ahead of the pursuing immune system.
1Snow, R.W.; Guerra, C.A, et. al. (2005) “The global distribution of clinical episodes of Plasmodium falciparum malaria“, Nature , pp. 214 – 217
2Sing, B.; Sung, L, et. al. (2004) “A large focus of naturally acquired Plasmodium knowlesi infections in human beings “, Lancet pp 1017 – 1024
3Arthralgia literally translates to “joint pain” and is commonly the result of illness, infection, allergic reaction to medication, or injury. Unlike true arthritis, it does not cause inflammation of the joint(s).
Source: Wikipedia.com ( http://en.wikipedia.org/wiki/Arthralgia )
4Idro, R., White, S., et. al. “Decorticate, decerebrate, and opisthotonic posturing and seizures in Kenyan children with cerebral malaria” Malaria Journal
5Gametocytes is a eukaryotic germ cell that divides by mitosis into other gametocytes or by meiosis into garnetids during gametogenesis.
Source: Wikipedia.com ( http://en.wikipedia.org/wiki/Gametocyte )
6Cogswell, F.B. (January 1992) “The hypnozoite and relapse in primate malaria“, Clinical Microbiology Review , pp. 26 – 35