Visceral leishmaniasis (VL) in South Asia is a serious disease affecting children and adults. Acute VL develops in only a fraction of those infected individuals, the majority being asymptomatic with the potential to transmit infection and develop disease. We followed 56 individuals characterized as being asymptomatic by sero-positivity with rk39 RDT in a hyper endemic district of Bangladesh to define the utility of Leishmania-specific antibodies and DNA in identifying infection. At baseline, 54 of the individuals were sero-positive with one or more quantitative antibody assays and antibody levels persisted at follow-up. Most sero-positive individuals (47/54) tested positive by qPCR at baseline, but only 16 tested positive at follow-up. The discrepancies among the different tests may shed light on the dynamics of asymptomatic infections of L. donovani, as well as underscore the need for standard diagnostic tools for active surveillance as well as assessing the effectiveness of prophylactic and therapeutic interventions.
Infection with Leishmania donovani is typically asymptomatic, but a significant number of individuals may progress to visceral leishmaniasis (VL), a deadly disease that threatens 200 million people in areas where it is endemic. While diagnosis of acute VL has been simplified by the use of cost-effective confirmatory serological tests, similar standardized tools are not widely available for detecting asymptomatic infection, which can be 4 to 20 times more prevalent than active disease. A simple and accurate serological test that is capable of detecting asymptomatic L. donovani infection will be useful for surveillance programs targeting VL control and elimination. To address this unmet need, we evaluated recombinant antigens for their ability to detect serum antibodies in 104 asymptomatic L. donovani-infected individuals (qualified as positive for L. donovani-specific antibodies by direct agglutination test [DAT]) from the Mymensingh district of Bangladesh where VL is hyperendemic. The novel proteins rKR95 and rTR18 possessed the greatest potential and detected 69% of DAT-positive individuals, with rKR95 being more robust in reactivity. Agreement in results for individuals with high DAT responses, who are more likely to progress to VL disease, was 74%. When considered along with rK39, a gold standard antigen that is used to confirm clinical diagnosis of VL but that is now becoming widely used for surveillance, rKR95 and rTR18 conferred a sensitivity of 84% based on a theoretical combined estimate. Our data indicate that incorporating rKR95 and rTR18 with rK39 in serological tests amenable to rapid or high-throughput screening may enable simple and accurate detection of asymptomatic infection. Such tests will be important tools to measure L. donovani infection rates, a primary goal in surveillance and a critical measurement with which to assess elimination programs.
Acute visceral leishmaniasis (VL) is caused by infection with parasites of the Leishmania donovani complex and may be fatal if not treated. Early diagnosis and efficacious treatment are the keys to effective VL management and control. Novel regimens are being developed to overcome limitations in VL treatment options, which are currently restricted by high costs, severe systemic side effects, and unresponsiveness. Although simple and accurate serological tests are available to help confirm VL, none are suitable to monitor treatment efficacy and cure. Here, we confirm that serum antibody responses to the diagnostic antigens rK39 and rK28 are unaltered by treatment, but demonstrate that antibodies produced against two antigens, rK26 and rK18, can be used as an indirect measure of parasite clearance. The levels of anti-rK18 and -rK26 antibodies were high in patients at initial diagnosis but declined in patients treated with either SSG (Ethiopia) or AmBisome (Bangladesh). Taken together, we propose that serological tests which measure antibodies to rK26 and rK18 merit consideration as potential markers of treatment success and cure.
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