Monday, February 20, 2012

Plasmodium- A smart parasite

This is a ppt copy of my presentation on Plasmodium in Explore-2012 CME, Manipal.

      The following is the summary of my talk, already published in "Genesis" by MLT department, MCOAHS, Manipal.
     Humans have been known to be effected from Plasmodium species from a very old time. This vector borne disease is transmitted by the female Anopheles group of mosquito. It is believed that this parasite has modified itself, along with human evolution and is with us since human race began. To date, P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi are found to be the etiological agents. It is estimated that, nearly 1 million deaths occur every year which is 1% of the infected population as per the WHO estimates.

     Plasmodium species belongs to Apicomplexa, is morphologically a drop shaped organism in asexual stage with various internal structures, of which rhoptry and microneme has been studied in depth owing to its importance in invasion of erythrocyte. The life cycle has been studied in detail. The parasite attacks the RBC and internalizes itself via a gliding movement, the details of which are still in question. On successful invasion a “Parasitophorous vacuole (PV)” is created and the organism takes control of the RBC machinery. The hemoglobin part is used as a nutrient and broken into components using various enzymes (Such as plasmepsin and others). A special enzyme called as Heme detoxification protein (HDP) is thought to convert the heme portion to hemozoin. This metabolite is a toxic waste and extruded from the PV which produces the ring appearance.

     The laboratory diagnosis is mostly by methods of microscopy. Thick and thin blood smears stained using Romanovsky stain or a QBC preparation is used singly or in combination with RDT (Rapid diagnostic tests). The RDT targets the HRP (Histidine rich protein) or pLDH. Though culture and molecular analysis is available the use in a diagnostic setting is still questioned, thanks to the cost. An expensive but very good method is to look for hemozoin in WBC population using its unique properties of light dispersion (Cell-Dyn automated blood cell analyzers). Speciation is usually by microscopy, which however doesn’t distinguish between P knowlesi and P malariae.

     Control of vector has not been effective. Avoiding exposure to mosquito by use of bed nets and IRS (Indoor residual spraying), or both has been effective. The CSP (circumsporozoite protein) expressed in the sporozoite has been found to contain a unique NANP repeat is being tested by GSK. Now known as RTS, S/AS01 Vaccine is under evaluation in a phase 3 trial. The preliminary results are showing a 50% protection, good leap from nothing. PfRH5 which has a strong affinity to CD147 has also been projected as possible vaccine candidate for falciparum species. 

     In nutshell, the pragmatic aspect of controlling malaria is good but elimination is not a possibility, at least as per the existing knowledge on plasmodium biology.

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