Tackling another source of malaria, Plasmodium vivax

October 25, 2012 § Leave a comment

A whole dissected An. gambiae female midgut is stained for actin (green), nuclei (blue) and midgut epithelial cells (red). Anterior midgut images depict varying intensities in staining of actin. 3-D homology model shows a luminal surface annexin-like molecule identified in the study, which is a putative ligand for P. vivax.
Image credit: Jonas King and Elizabeth Weissbrod.

The parasite Plasmodium falciparum is perceived as the only culprit of deadly malaria. But P. falciparum is not the only one of its kind. Plasmodium vivax also causes malaria that can be fatal. In a recent paper in Molecular & Cellular Proteomics, researchers have developed a workflow that delves into the transcriptomic and proteomic information of the mosquito, Anopheles albimanus, which is a vector of this equally devastating parasite to better understand parasite transmission biology and identify potential vaccine targets.

A lot is known about P. falciparum and its interactions with its main African vector, the mosquito Anopheles gambiae that transmits the parasite (An. gambiae’s genome was sequenced 10 years ago). The transmission of the parasite from its vector into humans has been the cause of malaria cases in Africa. Just in 2008, there were 243 million cases of malarial fever and about 863,000 deaths from the disease in Africa, mostly in children younger than the age of 2.

But research into P. vivax has been sorely neglected, simply because “the dogma was that malaria caused by P. vivax did not kill,” says Rhoel Dinglasan at the Johns Hopkins University School of Public Health, the corresponding author of the MCP paper. He adds it’s now becoming increasingly accepted that malaria caused by P. vivax is not benign.

About 3 billion people are at risk of contracting malaria from P. vivax, says Dinglasan. But because of the intense focus on P. falciparum and An. gambaie in Africa, Dinglasan says that most malaria scientists working in Central and South America, and Asia are not optimistic that research into P. vivax, which is rampant in those parts of the world, will get the appropriate backing. “Many of them whom I have met as a member of the International Vivax Consortium, which was sponsored by the Gates Foundation, are not convinced that they will ever see their mosquito vector of interest sequenced,” states Dinglasan.

For this reason, Dinglasan says it’s time to give equal emphasis to other causes of malaria. “I am a card-carrying member of the ‘malaria eradication bandwagon’ and clearly acknowledge that if we are ever to meet the goal of eradication, we cannot simply focus on P. falciparum malaria,” says Dinglasan.

So in the MCP paper, Dinglasan and colleagues described an analytical package that combined bioinformatics, transcriptomics and proteomics. They demonstrated how the package worked by using a midgut transcriptome of Anopheles albimanus, a vector for P. vivax in Central and South America, to guide a proteomic study of the mosquito’s midgut, the organ that supports the development of the parasite. When the transcriptome and proteome were used in conjunction with a protein database that the researchers custom-built for the Diptera order (to which the mosquitoes belong), the researchers were able to do a comparative proteomic analysis of the midgut of both An. gambiae and An. albimanus.

From their analyses, Dinglasan and colleagues were able to confirm that a novel vaccine that they are pursuing goes after a target conserved between the two mosquito subtypes. The vaccine blocks the transmission of the parasite from the mosquito to humans by targeting a protein in the mosquito midgut microvilli called alanyl aminopeptidase N.

Dinglasan says the investigators are hoping to use their approach to study intractable mosquito species in the Western Pacific, Bangladesh/India and Indochina. They want to understand the evolution of the mosquito midgut biology and its innate immunity.  This work will also help to confirm if the researchers are correct is pursuing alanyl aminopeptidase N as a vaccine target to broadly prevent malaria transmission, irrespective of the species of Anopheles mosquito and Plasmodium involved.

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