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MALARIA

Malaria is a serious and sometimes fatal disease caused by parasites that infect a type of mosquito that feeds on humans. About 2,000 cases of malaria are diagnosed in the US each year, with 216 million annual cases and 445,000 deaths worldwide. Nearly half of the world's population lives in areas at risk of malaria transmission. Malaria maintains a vicious cycle of disease and poverty, because many countries with malaria are already among the poorer nations, and the disease is a great drain on national economies with direct costs estimated at $12 billion/year.


The Pathogen 

Malaria is caused by a parasite infecting a mosquito that feeds on a human. There are 4 kinds of malarial parasites that infect humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariaeP. falciparum has many proteins with a role in its pathogenesis, such as invasion of red blood cells (RBCs), cytoadherence, and evading the immune system. PfEMP1, erythrocyte membrane protein 1, is key for P. falciparum to adhere to red blood cells. The parasite can change the PfEMP1 protein they express, which helps avoid detection from the host's antibodies. P. falciparum also use a group of proteins - Merozite Surface Proteins (MSPs) to invade into RBCs, the variation of these proteins enabling the parasite to invade antigenically different RBCs.  These proteins could explain why P. falciparum is the predominant species in the world compared to the other 3 malarial parasites.

Malaria Infections

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The clinical presentation in humans can vary depending on the infecting parasite species, the amount of parasites present, and the immune status of the patient. Initially the parasites grow and multiply in the liver cells and then in the red cells of the blood. In the blood, successive broods of parasites grow inside the red cells and destroy them, releasing daughter parasites (“merozoites”) that continue the cycle by invading other red cells.The blood stage parasites are those that cause the symptoms of malaria. The most frequent symptoms are fever and chills, which can be accompanied by headache, vomiting and diarrhea. This can lead to loss of red blood cells, low numbers of platelets, lung or liver dysfunction, and neurologic changes.


Malarial Antibiotic Resistance

The development of resistance to drugs poses one of the greatest threats to control of malaria, increasing malarial morbidity and mortality. In two of the four human malarial parasite species, P. falciparum and P. vivax, resistance has already been detected. Chloroquine-resistant P. falciparum was first detected in the late 1950s, while chloroquine-resistant P. vivax was first identified in 1989. P. falciparum has also developed resistance to nearly all of the currently available antimalarial drugs, such as sulfadoxine/pyrimethamine, mefloquine, halofantrine, and quinine. Recently resistance to the artemisinin-based combination therapy has emerged, impacting the efficacy of this vital antimalarial class.