Understanding red blood cell invasion by the malaria parasite

Yaw Aniweh is a Ghanaian research fellow at the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), one of the eleven Developing Excellence, Leadership, and Training in Science in Africa (DELTAS Africa) programmes, which fund Africa-based scientists to amplify the development of world-class research and scientific leadership on the continent while strengthening African institutions. DELTAS Africa is implemented through the Alliance for Accelerating Excellence in Science in Africa (AESA), a funding, agenda-setting, programme management initiative of the African Academy of Sciences (AAS), the African Union Development Agency (AUDA-NEPAD), founding and funding global partners, and through a resolution of the summit of African Union Heads of Governments. DELTAS Africa is supported by Wellcome and the United Kingdom Foreign, Commonwealth and Development Office (FCDO, formerly DFID).

Summary

Malaria remains a major global challenge with recent reports of about 216 million cases and 445,000 deaths worldwide. The successes gained by malaria control strategies are threatened by the development and spread of antimalarial drug-resistant parasites and insecticide-resistant mosquitoes. Plasmodium falciparum, the species of parasite known to cause the most deaths, exhibits high levels of genetic diversity which has amplified drug resistance and hampered the development of effective malaria vaccines. The development of a durable and effective vaccine remains a key priority in the fight against malaria in an era of renewed global interest in elimination and eradication. Erythrocyte (red blood cell) invasion remains a key area for vaccine development and for the formulation of other interventions to stop the disease. Yaw’s study focuses on understanding the invasion mechanisms of the parasite with an aim to develop strategies to stop it.

Background

Malaria continues to be a global health threat in resource-limited settings. It is still the leading cause of death in infants and pregnant women in Africa. Human malaria is caused by several species of the Plasmodium parasite, with the severest form of the disease attributed to Plasmodium falciparum. The parasite has a complex life cycle, making it difficult to develop interventions to halt transmission and morbidity. Transmitted by mosquitoes, the parasite’s sexual development occurs in the mosquito. The parasite quickly moves to the liver once it is introduced into the human body through a mosquito bite. The parasite then develops in the liver until it is released into the blood, at which stage the disease manifests, following the invasion of the parasite into the red blood cells. Since the blood stage of the parasite is directly correlated to the disease, understanding the process by which the parasite enters human red blood cells is very important in developing interventions to prevent disease.

Description of the study

Dr Yaw Aniweh led a study that focused on the variation in transmission dynamics and the changing ecological zones of this malaria parasite in Ghana in order to understand the factors driving red blood cell invasion across the country. The study analysed parasite samples from the clinic and evaluated how they differ across various clinical settings. Whereas assays have conventionally been developed using laboratory strains, (laboratory-grown types/forms of the malaria parasite) this study focused on the use of field isolates, providing an alternative understanding of the parasite’s biology. An assay is a laboratory test to find and/or measure the amount or quality of a specific substance; in this case, the malaria parasite. The study successfully profiled over 200 parasite isolates across Ghana for their mechanism of invasion, which is complex in the case of P. falciparum. Blood cells invasive form of the parasite (Merozoites) enter human red blood cells using molecules on the merozoites and the molecules on the human red blood cells surface. Because it is known that some parasite molecules, such as the recticulocyte-binding protein homologs (PfRHs), play a key role in the parasite invasion of red blood cells, Dr. Aniweh and his team evaluated the role of members of this protein family during the invasion process. They evaluated PfRH2b deletion dynamics across Ghana and many other countries and found that PfRh2b-specific region deletion is widespread. As an extension of the study, the team is currently using clinical isolates in exploring why the parasite chooses to delete this region.

The study also explored possible parasite molecules that play a role in inducing protection in patients, which led to the identification of a molecule in P. falciparum, we called the molecule (PfMAAP). This protein is under further study for its viability as a vaccine candidate.

Impact

1. The study’s use of clinical isolates from different parasite populations demonstrates the need to evaluate the dynamics associated with the development of interventions, which may provide some insight as to their potential success. The study makes a case for the consideration of factors such as changes in transmission dynamics as well as the effect of ecological differences on malaria outcomes.
2. The newly identified parasite molecule PfMAAP is being evaluated at the pre-clinical stage as a possible malaria vaccine candidate.
3. The project has generated a large number of parasites from clinics which will help in understanding transmission dynamics of the parasite from different areas and contribute to the identification of unique biological mechanisms for the development of interventions.
4. New tools have been generated to help study the biology of other Plasmodium species that cause malaria. With these tools, we can understand the biology of these parasites, which contributes to formulating a comprehensive approach towards sustaining the goal of control and eventual elimination of malaria.