Scientists at the U.S. Food and Drug Administration (FDA), in collaboration with the Johns Hopkins Malaria Research Institute, identified changes in the expression of specific genes of human malaria parasite Plasmodium falciparum as they undergo development in the mosquito midgut. These newly identified genes/antigens could become the basis of an improved test for monitoring the disease burden in countries where malaria is transmitted.

Malaria is a serious infection that causes high fevers, shaking chills, and influenza-like illness. The parasite, called Plasmodium, is spread by Anopheles mosquitoes that acquire the parasite when taking a blood meal from an infected person. There are about 250 million cases of malaria and 550,000 deaths each year, mostly in sub-Saharan Africa and South Asia. In addition, more than 38 million Americans travel to parts of the world where malaria is common.

The current test used to identify mosquitoes carrying the malaria parasite detects a molecule called the circumsporozoite protein, which is secreted by a form of the parasite called the sporozoite. However, this test cannot detect the protein until seven days after the mosquito takes a blood meal from an infected human.

The FDA findings are important because efforts to control malaria face potential roadblocks, such as lack of resources for early detection and treatment, emerging resistance against most effective and commonly used anti-malarial drugs, population growth, climate changes that help spread mosquitoes carrying the parasite, and difficulties in launching sustained efforts to reduce the spread of the disease in countries where it is widespread. A test that enables detection of the parasite several days earlier than is now possible would provide a timely picture of how widespread the infected mosquitoes are in an area. It would also help measure the effectiveness of prevention strategies such as vaccination programs, the use of bed nets to deter mosquito bites, and insecticides in areas where the disease was known to be widespread.

The scientists mapped gene activity in a form of the parasite called the oocyst, which migrates to the midgut of the mosquito after it takes a blood meal. There, the oocyst produces sporozoites, forms of the parasite that migrate to the mosquito’s salivary gland, from where they are inoculated into humans during a subsequent blood meal.

The scientists identified the RNA molecules made by the oocyst stage of the parasite in mosquitoes on days 2, 4, 6, and 8 after they had fed on human red blood cells infected with Plasmodium. Among these genes they identified are those that are expressed (make RNA from the DNA code) only at one of those times points, as well as genes that are expressed at all four times points. This enabled the scientists to identify “signatures” of gene activity and the production of specific proteins by those genes that can identify parasites within the mosquito as early as the second day after a blood meal.

TITLE

Transcriptome analysis based detection of Plasmodium falciparum development in Anopheles stephensi mosquitoes

Scientific Reports volume8, Article number:11568 (2018)

AUTHORS

Miranda S. Oakley¹, Nitin Verma², Timothy G. Myers³, Hong Zheng², Emily Locke⁴, Merribeth J. Morin⁴, Abhai K. Tripathi⁵, Godfree Mlambo⁵ & Sanjai Kumar²

1. Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review, Food and Drug Administration, Silver Spring, MD, USA
2. Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA
3. Microarray Research Facility, Research and Technologies Branch, National Institutes of Health, Bethesda, MD, USA
4. PATH’s Malaria Vaccine Initiative, Washington, DC, USA
5. Johns Hopkins Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology, Baltimore, MD, USA