The chameleon-like nature of the malaria parasite.

Malaria remains a major cause of childhood deaths worldwide. However, the reasons why some children get life threatening disease and others only suffer mild symptoms are still poorly understood.

A new paper by Dr George Warimwe and other KEMRI-Wellcome Trust Researchers suggests that the significant differences in malaria symptoms among African children might have something to do with the parasite’s expression of sticky surface antigens known as PfEMP1 on the surface of the human red blood cells that it infects.  The paper, Prognostic Indicators of Life-Threatening Malaria Are Associated with Distinct Parasite Variant Antigen Profiles, was released on 11^th April, 2012 by the Science Translational Medicine Journal and abstract is available here.

According to the study, Plasmodium falciparum , the parasite responsible for the most severe form of malaria  , can display  multiple alternative forms of of the PfEMP1 molecules on the surface of the infected red blood cells. In this way it can shift and change its appearance thus avoiding being caught by the host’s immune system. 

As Dr Pete Bull, the lead author of the paper explains “The malaria parasites are chameleon like in that they shift and change by switching between PfEMP1 molecules. We think that PfEMP1 switching can help explain the large variation in how the disease is experienced. This may in the future help in rationalizing different treatment strategies”  

The study was focused on the two major manifestations of life-threatening malaria in hospitalized African children: respiratory distress and impaired consciousness. The authors studied malaria parasites sampled from children with these manifestations and found that the properties of these parasites differed from each other and from parasites obtained from children without these clinical manifestations. Children with respiratory distress tended to be infected with parasites that make the red blood cells they infect bind to other uninfected red blood cells (a phenotype called “rosetting”)In contrast, parasites from children with impaired consciousness frequently expressed high levels of a subset of PfEMP1 variants called “group A–like” PfEMP1 without exhibiting high levels of rosetting. The authors suggest that different manifestations of malaria may be associated with distinct types of the host-parasite interaction. This will help to focus efforts to standardize the phenotyping of the disease and may help in the development of specific interventions in the future.

Commenting on the study results, Dr Bull said that “Our study put a particular emphasis on the two major clinical indicators of life threatening malaria in African children but in the end, it is the cumulated evidence from different settings that will be important. With this type of question, we should not rely too heavily on single studies, and we do need to start standardizing the way we do these studies so that we can start making proper comparisons over time and in different parts of the world.”

Citation: G. M. Warimwe, G. Fegan, J. N. Musyoki, C. R. Newton, M. Opiyo, G. Githinji, C. Andisi, F. Menza, B. Kitsao, K. Marsh, P. C. Bull, Prognostic Indicators of Life-Threatening Malaria Are Associated with Distinct Parasite Variant Antigen Profiles. Sci. Transl. Med. 4, 129ra45 (2012).

Image: An uninfected red blood cell, source Wellcome Trust Images