An investigation of host responses to malaria during co-infection with schistosomiasis

Malaria and schistosomiasis are the most prevalent tropical diseases in sub-Saharan Africa and exert a huge burden of mortality, morbidity as well as contributing to underdevelopment of already disadvantaged populations. More than 50% of the world population is at risk of malaria and approximately 500 million clinical cases of malaria are reported each year, whereas at least 650 million people are at risk and about 200 million people are infected with schistosomiasis. The geographical and epidemiological overlap of these diseases commonly occur making concomitant infection highly probable. It is not clear how helminth infections modulate the immune responses towards the malaria parasites and affect the outcome and course of malaria. The effect of concomitant infection of hosts by schistosomiasis and malaria was investigated in a mouse model in the laboratory under controlled conditions as well as under field conditions in children aged 6 to 17 in an area in which both diseases were endemic. We found that patent Schistosoma mansoni infection in BALB/c mice significantly increased malaria peak parasitemia and caused death of mice from an otherwise non-lethal, self-resolving Plasmodium yoelii malaria infection. This exacerbation of malaria parasitemia occurred both in pre-patent and in patent S. mansoni infection of mice and resulted in a significant delay in the malaria parasite clearance by the co-infected mice. Praziquantel treatment of schistosome-infected mice protected from fatal outcome though it did not reduce the peak malaria parasitemia reached. On the other hand, human field studies revealed a higher prevalence of Plasmodium falciparum malaria parasites in children with schistosomes (31%) compared to children free from schistosomes (24%). In addition, a higher proportion of co-infected children had sexual stage malaria parasites (gametocytes) and at a higher gametocyte load in peripheral blood compared to the malaria-only infected children, implying a possible higher malaria transmitting potential. We found similar plasma reactivity to malaria antigens between co-infected and malaria-only infected children. However, growth inhibition activity was higher for malaria-only infected children compared to their co-infected counterparts. This observation suggests an essential difference in the effectiveness of antibodies produced in blocking erythrocyte invasion by malaria parasites in the two situations, which warrants further investigation.