VIOLIN: Vaccine Investigation and Online Information Network

Pathogen Page

Plasmodium spp.

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Malaria

3. Introduction

Malaria is a vector-borne infectious disease that is widespread in tropical and subtropical regions, causing disease in approximately 400 million people and killing 1-3 million, most of them young children in Sub-Saharan Africa. It is one of the most common infectious diseases, caused by protozoan parasites of the genus Plasmodium. The most serious forms of the disease are caused by P. falciparum and P. vivax, but other related species (P. ovale, P. malariae, and sometimes P. knowlesi) can also infect humans. This group of human-pathogenic Plasmodium spp. is usually referred to as malaria parasites and are transmitted by female Anopheles mosquitoes. The parasites multiply within red blood cells, causing symptoms of anemia, as well as other general symptoms such as fever, chills, nausea, flu-like illness, and in severe cases, coma and death. No vaccine is currently available for malaria; preventative drugs must be taken continuously to reduce the risk of infection. These prophylactic drug treatments are often too expensive for most people living in endemic areas. Most adults from endemic areas have a degree of long-term recurrent infection and also of partial resistance, which 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 (Joy et al., 2003; Escalante et al., 1998; Kaufman et al., 2005; Meis et al., 1983).

4. Microbial Pathogenesis

Malaria in humans develops via exoerythrocytic (hepatic) and erythrocytic phases. 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 the human host, they infect hepatocytes, multiplying asexually and asymptomatically for a period of 6–15 d. During this "dormant" time in the liver, the sporozoites are often referred to as "hypnozoites". Once in the liver, these organisms differentiate to yield thousands of merozoites which, following rupture of their host cells, escape into the blood and infect red blood cells, 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 erythrocytes, the parasites multiply further, periodically breaking out of their hosts to invade fresh erythrocytes. Several such amplification cycles occur, resulting in the classical waves of fever. Some merozoites turn into male and female gametocytes. 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 stillbirths, infant mortality and low birth weight (Talman et al., 2004; Bledsoe, 2005; Sturm et al., 2006).

5. Host Ranges and Animal Models

The vast majority of malaria cases occur in children under the age of 5 years; pregnant women are also especially vulnerable. Despite efforts to reduce transmission and increase treatment, there has been little change in which areas are at risk of this disease since 1992. Precise statistics are unknown, as the majority of cases are undocumented. Although HIV/malaria co-infection produces less severe symptoms than the interaction between HIV and TB, HIV and malaria do contribute to each other's spread. This effect comes from malaria increasing viral load and HIV infection increasing a person's susceptibility to malaria infection. Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; however, it is in sub-Saharan Africa where 85– 90% of malaria fatalities occur. The geographic distribution of malaria within large regions is complex, and malarial and malaria-free areas are often found close to each other. In drier areas, outbreaks of malaria can be predicted with reasonable accuracy by mapping rainfall (Breman, 2001; Greenwood et al., 2005; Hay et al., 2004).

6. Host Protective Immunity

Plasmodia are relatively protected from attack by the body's immune system because for most of its life cycle it resides within liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, P. falciparum displays adhesive proteins on the surface of the infected blood cells, causing blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen and giving rise to hemorrhagic complications. Endothelial venules can be blocked by the attachment of masses of these infected red blood cells (RBCs). The blockage of these vessels causes placental and cerebral malaria. Although the RBC 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 (Chen et al., 2000; Adams et al., 2002).

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