Concomitant infection with Leishmania donovani and Plasmodium berghei alters clinical and immune responses in BALB/c mice

Abstract

Malaria and visceral leishmaniasis coexist in the same geographical regions. However, dual co-infection with parasites causing these diseases and their impact on public health is poorly documented. Interactions between these parasites may play a role in disease outcome. The present study set out to evaluate the clinical and immunological parameters following Leishmania donovani and Plasmodium berghei co-infection in BALB/c mice. Mice were divided into four groups; L. donovani- only, L. donovani- P. berghei, P. berghei- only and naive. Body weight, parasite burden, total IgG, IFN-{gamma} and IL-4 responses were determined. To determine the survival rate, four mice were used from each group. Tissues for histological analysis were taken from spleen, liver and brain. Results indicated significant differences in body weight (P<0.0001), L. donovani parasite load (P< 0.0001), L. donovani IgG (P< 0.0001), P. berghei parasitemia (P= 0.0222), P. berghei IgG (P= 0.002), IFN-{gamma} (P<0.0001) and IL-4 (P<0.0001) in dual-infected mice. There was no correlation between L. donovani parasite load and IgG responses in single or dual infections, while there was a positive relationship of P. berghei parasitemia and IgG responses in the dual infection group only. Plasmodium berghei had the highest mortality rate compared to L. donovani- only and L. donovani- P. berghei infected mice groups. Histological analyses showed enlarged red and white pulps and pathological changes in the spleen, liver and brain tissues which were less pronounced in co- infected group. We conclude that L. donovani and P. berghei co-infection reduces disease severity and these changes seem to correlate with variation in serum IgG and cytokines (IFN-{gamma} and IL-4). Therefore, the study recommends the importance of inclusion of early screening of malaria in Visceral Leishmaniasis patients in regions where malaria is co- endemic. Author SummaryVisceral leishmaniasis and malaria are the principal causes of morbidity and mortality affiliated with parasitic diseases universally warranting the necessity to investigate the control and immunology of the infections. Notwithstanding the probable incidences of leishmaniasis- malaria infections in endemic regions are not readily eminent to the clinicians if an individual is co-infected and almost frequently, such patients develop a fever and are customarily treated against malaria and hence the need to study disease progression and outcome during a co- infection. Furthermore, it is unclear if this co-infection could impede the clinical symptoms of the separate diseases and thus the necessity to demonstrate disease outcome in experimentally co-infected murine models. This present study was crucial to find out whether this mode of co- infection alters disease progression and enhanced severity leading to high morbidity and mortality. This current research was an imperative step in using murine as a model in the study of disease outcome and immunopathogenesis of visceral leishmaniasis and malaria co-infection thus establishing the feasibility of co-infecting the BALB/c mice with Leishmania donovani and Plasmodium berghei.