Biomarkers in Parasitic Infections

Parasitic infections are still endemic in developing countries. Role of biomarkers in two common parasitic infections, malaria and schistosomiasis, will be discussed here. Biomarker studies in parasitic infections are complicated by the simultaneous infection with multiple parasites in the same individual.

Role of Biomarkers in Malaria

The incidence and severity of malaria infection continue to be on the rise in many parts of the world. The situation is exacerbated by the emergence of multidrug resistance to Plasmodium falciparum and P. vivax, the two most important human malaria parasites. Malaria is a complex infectious disease in which the host response to infection is dependent upon the parasite stage, parasite virulence factors, and host genetic background. Diagnosis can be established by identification of the parasite in blood smears. There is still a need to understand the molecular processes that regulate transcriptional activity and gene networks involved in the pathogenesis of or protection from disease as they may provide insights into protective mechanisms of immunity that aid in the design of more effective vaccines.

An analysis of the gene expression profiles has identified a set of host biomarkers, which distinguish between lethal and nonlethal blood stage murine malaria infections with P. yoelii. Multiple biological replicates sampled during the course of infection were used to establish statistically valid sets of differentially expressed genes. Genes that correlated with the intensity of infection were used to identify pathways of cellular processes related to metabolic perturbations, erythropoiesis, and B-cell immune responses and other innate and cellular immune responses. Provide insights into transcriptional regulatory mechanisms that influence both the pathogenesis of disease and the host’s recovery from infection. While immune responses in human P. falciparum and P. vivax malaria may share many similar features of the global gene expression program observed in murine malaria, important differences in expression profiles in humans infected clinically or experimentally with malaria will depend on the type of tissue (peripheral blood, bone marrow, spleen, or brain) and the stage of infection (early asymptomatic versus clinical malaria) that is studied.

Because acquisition and maintenance of antimalarial antibodies depend on exposure to malaria infection, such antibodies might be used as biomarkers of transmission intensity. Measurement of these antiboies by serological tests may detect variations in malaria transmission over time and will be invaluable for monitoring trends in malaria endemicity and the effectiveness of malaria control programs (Drakeley et al. 2005). Molecular biomarkers have been investigated for assessing resistance to antimalarial drugs but no conclusive information is available as yet. Efforts to use plasma levels of sTNF-R75 and circulating parasite DNA to estimate sequestered loads of P. falciparum have not been successful so far.

It is important to identify individuals infected with P. falciparum who are at risk of developing serious complications such as cerebral malaria. Serum angiopoietin-1 and the angiopoietin-2/1 ratio are promising clinically informative biomarkers for cerebral malaria (Lovegrove et al. 2009). Further studies should address their usefulness as prognostic biomarkers and potential therapeutic targets in severe malaria.

 
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