title: Accurate Serodetection of Asymptomatic Leishmania donovani Infection by Use of Defined Antigens.
abstract: Infection with Leishmania donovaniis 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 asymptomaticL. donovaniinfection 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 asymptomaticL. donovani-infected individuals (qualified as positive forL. 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 measureL. donovaniinfection rates, a primary goal in surveillance and a critical measurement with which to assess elimination programs.
authors: Infectious Disease Research Institute, Seattle, Washington, USA.
authors: Aarthy C
authors: AC
authors: Vallur
authors: Infectious Disease Research Institute, Seattle, Washington, USA.
authors: Caroline
authors: C
authors: Reinhart
authors: Infectious Disease Research Institute, Seattle, Washington, USA.
authors: Raodoh
authors: R
authors: Mohamath
authors: Infectious Disease Research Institute, Seattle, Washington, USA.
authors: Yasuyuki
authors: Y
authors: Goto
authors: International Center for Diarrhoeal Diseases Research, Laboratory Sciences Division, Dhaka, Bangladesh.
authors: Prakash
authors: P
authors: Ghosh
authors: International Center for Diarrhoeal Diseases Research, Laboratory Sciences Division, Dhaka, Bangladesh.
authors: Dinesh
authors: D
authors: Mondal
authors: Infectious Disease Research Institute, Seattle, Washington, USA.
authors: Malcolm S
authors: MS
authors: Duthie
authors: Infectious Disease Research Institute, Seattle, Washington, USA sreed@idri.org.
authors: Steven G
authors: SG
authors: Reed
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D058070:Asymptomatic Diseases; D001459:Bangladesh; D006801:Humans; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000175:diagnosis*; D011994:Recombinant Proteins / Q000276:immunology; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D011994:Recombinant Proteins