Malaria parasites found to reside in bone marrow
Malaria is an infectious disease which claims the lives of more children worldwide than any other; it is caused by parasitic micro-organisms, plasmodiums. These parasites are transmitted to their hosts via mosquito bites, where they induce a range of symptoms, including vomiting, fever, headaches, and, in severe cases, death. Incidence of malaria is prevalent in poverty stricken areas around the equator, with an estimated 207 million cases in 2012. The most life threatening form of the disease is caused by Plasmodium falciparum.
Within humans, P. falciparum undergoes two distinct stages, asexual replication, and differentiation into what are called gametocytes. Asexual replication occurs within red blood cells, with pathological symptoms arising from the inevitable red blood cell rupturing. Released parasites generally invade additional red blood cells for subsequent rounds of asexual replication; however, a small subset of parasites instead differentiate into the male and female forms that are refered to as gametocytes. Once taken up by a female Anopheles mosquito, these gametocytes are able to undergo sexual replication. Thus, the differentiation of P. falciparum into gametocytes represents an attractive target for intervention strategies. However, within the blood only mature gametocytes are found, and until recently, relatively little was known about immature gametocyte sequestration within tissues.
A recent study carried out a systematic organ survey of children who died from malaria, successfully identifying sites of immature gametocyte accumulation using a combination of immunohistochemical labelling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The study provides strong evidence that gametocyte development occurs within the haematopoietic system present in the bone marrow, where they may form and develop within red blood cell precursors. Furthermore, binding interactions with red blood cell precursors seem to support the retention of developing gametocytes within the bone marrow’s extravascular space, where they are able to avoid immune detection until they are mature enough to be released back into the blood. The observation of gametocytes adopting a specialised niche within the haematopoietic system of the bone marrow is supported by an independent study, which earlier this year used qRT-PCR to demonstrate that the bone marrow of infected children is enriched for immature gametocytes.
The recently characterised locations and mechanisms of gametocyte sequestration within the bone marrow, provide novel targets through which malaria transmission could be blocked, advancing both prevention and treatment efforts.
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