Parasitic Diseases A Focus On Malaria

Parasites — cellular organisms that can only exist in or on a host — affect almost all forms of life, including animals and humans. An estimated 2 billion humans are infected with at least one parasite. Parasites are classified as endoparasites or ectoparasites depending on whether they live in or on a host. Human parasites generally fall into two main categories: (1) protozoa (one-celled oreukary-otic organisms) and (2) multicellular organisms such as worms (helminths) and insects.

In this section we shall consider only diseases that are caused by endoparasites. Infections by protozoa cause diseases such as malaria, leishmaniasis, sleeping sickness, and chronic diarrhea. Infection by parasitic worms (e.g., roundworms or nematodes, flukes or trematodes, tapeworms or cestodes) results in other diseases, for instance river blindness. Virtually all parts of the human body are vulnerable to parasites. Leishmaniasis affects the skin and spleen; onchocerciasis (river blindness) affects the skin and eyes; giardiasis and crytosporidiosis affect the gut; and malaria affects the blood and central nervous system.

Of all parasitic diseases, malaria is the deadliest since it results in 2.5 million deaths annually. Malaria is caused by the protozoan Plasmodium that is spread from human to human by mosquito bite. Plasmodium consists of nine species, four of which cause malaria in humans. The life cycle of the most infectious species, Plasmodium falciparum is shown below. Human and mosquito hosts are both essential for survival of the parasite. The life cycle starts with an asexual phase and progresses to the later phases that are sexual in nature. The sporozoite forms of the parasite enter the human host through the saliva of the mosquito when it penetrates the skin and withdraws blood. Sporozoites reach the liver in 30 minutes through the blood and infect liver cells. The hepatic stage of the infection lasts for 6-15 days, during which time thousands of daughter parasites, merozoites, are formed. Next, the infected liver cells burst and release thousands of merozoites which go on to infect erythrocytes - red blood cells -and multiply further (erythrocytic stage). The erythrocytes burst and newly formed merozoites are released, causing the generation of cytokines which then lead to fever and chills, the usual symptoms of malaria. Some erythrocytic merozoites enter a sexual phase In which male and female gametocytes are formed. These can be transformed into male and female gametes only in the mosquito gut. There, through many steps, new sporozoites are formed and await injection into another human host to continue the life cycle. The drugs that act on the various stages of the cycle are highlighted in yellow boxes in the figure below.1"3

1 Curr Med. Chem. 2007. 14, 289-314; 2. Med. Res. Rev. 2007, 27. 65-107; 3. Mini-Rev. Med. Chem. 2006, 6, 177202; Refs. p. 179

ATOVAQUONE

HEPATIC STAGE

1 Curr Med. Chem. 2007. 14, 289-314; 2. Med. Res. Rev. 2007, 27. 65-107; 3. Mini-Rev. Med. Chem. 2006, 6, 177202; Refs. p. 179

ATOVAQUONE

HEPATIC STAGE

Gametocytes are transferred to the mosquito gut via blood

Offspring sporozoites In the mosquito gut

Male and female gametes in the mosquito gut

Gametocytes In the mosquito gut

Gametocytes are transferred to the mosquito gut via blood

Offspring sporozoites In the mosquito gut

Male and female gametes in the mosquito gut

Gametocytes In the mosquito gut

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