Pre-erythrocytic (liver) stage

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The initial infection

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The initial mosquito bite (Image A): blood from the host is taken through the mosquito mouthparts (m) from small vessels (v). At the same time fluid from mosquito salivary glands passes into the vessel. When a mosquito is host to the malaria organism then parasites enter the blood with this saliva (in the form of "sporozoites" (sp)). Infection and replication in liver The sporozoites that have entered the blood then pass through the blood vessel and into the cells of the liver (B). They may pass through multiple cells but then remain in a single liver cell (C). From liver to blood The parasites in liver cells (D) then undergo repeated cycles of asexual replication (E) to form schizonts which are similar to the schizont stage in blood. At the end of the process the “merozoites” that are formed are released into blood (F). They then infect red cells and now have the typical appearance of early trophozoite (G). Relevance of hepatic stage to clinical biology The hepatic stage is the period where parasites begin to replicate and cause infection - this corresponds to an incubation period before symptoms begin; this will typically last between 1-4 weeks, and during this time parasites will not be detected in blood. The number of bites required for infection may be only 1 if the mosquito is heavily infected (hence cases of airport malaria where the infection is acquired from a mosquito passenger in luggage). For two malaria species (P.ovale and P.vivax) the hepatic stage may lie dormant for a period of time - this is the hypnozoite (“sleeping animal”). This hyponozoite may reactivate - typically in less than a year although occasionally longer, causing clinical malaria symptoms long after the initial infection. Further reading and sources DPDx - Malaria - Centers for Disease Control and Prevention (CDC) Malaria Parasite Liver Infection and Exoerythrocytic Biology - National Center for Biotechnology Information (NCBI) Lifecycle of the malaria parasite - Medicines for Malaria Venture (MMV)