Decreased prevalence of sepsis but not mild or severe P. falciparum malaria is associated with pre-existing filarial infection

Background: Enhanced inflammatory host responses have been attributed as the cellular basis for development of severe malaria as well as sepsis. In contrast to this, filarial infections have been consistently reported to be associated with an immunological hypo-responsive phenotype. This suggests that successful control of filariasis by employing mass drug administration, could potentially contribute to an increase in incidence of sepsis and cerebral malaria in human communities. A case control study was undertaken to address this critical and urgent issue. Methods: Eighty-nine patients with sepsis and one hundred and ninety-six patients with P. falciparum malaria all originating from Odisha, were tested for prevalence of circulating filarial antigens - a quantitative marker of active filarial infection. Antibodies to four stage specific malarial recombinant proteins were measured by solid phase immunoassays and circulating CD4+CD25(high) T-cells were quantified by flow cytometry with an objective to study if pre-existing filarial infections influence antibody responses to malarial antigens or the levels of circulating T-regulatory cells in P. falciparum infected patients. Results: Prevalence of filarial antigenemia was significantly less in sepsis patients as compared to controls suggesting that pre-existing filariasis could influence development of sepsis. On the other hand, levels of circulating filarial antigen were comparable in severe malaria cases and healthy controls suggesting that development of severe malaria is independent of pre-existing W. bancrofti infections. Plasma TNF-a, RANTES and antibodies to recombinant malarial proteins as well as levels of circulating CD4+CD25(high) cells were comparable in malaria patients with or without filarial infections. Conclusions: These observations imply that successful control of filariasis could have adverse consequences on public health by increasing the incidence of sepsis, while the incidence of severe malaria may not adversely increase as a consequence of elimination of filariasis.