Significantly Lower Anti-Leishmania IgG Responses in Sudanese versus Indian Visceral Leishmaniasis

Background Visceral leishmaniasis (VL), a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum), is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT), has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response. Methodology/Principal Findings We determined IgG titres of Indian and Sudanese VL patients against whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients had significantly higher IgG titres against both L. donovani strains compared to Sudanese VL patients (p<0.0001). Mean reciprocal log(10) 50% end-point titres (1/log(10)t(50)) were i) 3.80 and 3.88 for Indian plasma and ii) 2.13 and 2.09 for Sudanese plasma against Indian and Sudanese antigen respectively (p<0.0001). Overall, the Indian VL patients therefore showed a 46.8-61.7 -fold higher mean ELISA titre than the Sudanese VL patients. The higher IgG titres occurred in children (<16 years old) and adults of either sex from India (mean 1/log(10)t(50): 3.60-4.15) versus Sudan (mean 1/log(10)t(50): 1.88-2.54). The greatest difference in IgG responses was between male Indian and Sudanese VL patients of 16 years old (mean 1/log(10)t(50): 4.15 versus 1.99=144-fold (p<0.0001). Conclusions/Significance Anti-Leishmania IgG responses among VL patients in Sudan were significantly lower than in India; this may be due to chronic malnutrition with Zn2+ deficiency, or variable antigenicity and capacity to generate IgG responses to Leishmania antigens. Such differential anti-Leishmania IgG levels may contribute to lower sensitivity of the rK39-ICT in East Africa. Author Summary Visceral leishmaniasis (VL) is a systemic disease with highest prevalence in South Asia, East Africa, and Brazil. VL is caused by protozoan parasites of the Leishmania donovani complex, transmitted to humans when an infected sandfly takes a bloodmeal. Within the human host, the parasites replicate within cells, particularly of bone marrow and spleen. Without effective treatment, symptomatic VL is usually fatal. Correct treatment depends on accurate diagnosis, which is by detection of parasites or specific antibodies. The rK39 rapid diagnostic test for antibody is highly sensitive in South Asia but less so in East Africa, for poorly understood reasons. Here, we have directly compared the anti-Leishmania antibody response in groups of VL patients from India and Sudan. We found a strikingly higher anti-Leishmania antibody response in Indian compared to Sudanese patients, which was also seen when further analysed by age and sex of the patients. Thus in addition to parasite factors, we have shown that difference in antibody levels may contribute to the lower sensitivity of antibody-based diagnosis for VL in Sudan.