Predicting visceral leishmaniasis in HIV infected patients: how to screen and who to treat (PREDICT.VL)

HIV has been identified as one of the emerging challenges for control of visceral leishmaniasis (VL). This problem is now especially severe in Ethiopia – a L. donovani endemic region ‐ where up to 40% of patients with VL are co‐infected with HIV. Once VL is established in HIV‐infected individuals‐ meaning that L donovani infection has evolved to the disease stage ‐ prognosis at the individual level is dire, with high rates of case fatality (reaching 25%), treatment failure (up to 50%) and relapse (up to 60%). Tackling Leishmania infection before disease onset would thus be a logical approach.
Increasingly, it has been recognized that asymptomatic infections outnumber VL cases in most regions.
Although not fully understood, the outcome of Leishmania infection (ranging from parasite clearance to VL) is thought to be largely determined by immunological factors. This has however never been studied in depth on a background of HIV immune suppression. Importantly, in striking contrast with immunocompetent individuals where the risk of disease progression after infection is relatively low, and treatment of asymptomatic cases is currently not recommended, the situation might be entirely different in HIV‐coinfected, immunosuppressed individuals. We hypothesize that the period of asymptomatic Leishmania infection constitutes a window of opportunity for screening strategies, to capture those at high risk of VL. However, the basic understanding and evidence underpinning such a screening approach is currently lacking.
We propose to conduct a multi‐centre prospective cohort study including HIV‐positive adults enrolled in HIV care in a VL endemic region in North‐Ethiopia. Since 2009 we have established a clinical research network in this region that provides a unique platform for studying the clinical aspects of asymptomatic Leishmania infection and exploring a screening approach. Within the study area, we have identified two HIV clinical cohorts, with a total of over 3000 HIV‐infected patients in follow‐up. As residents of this region with high VL‐endemicity, they are exposed to Leishmania donovani infection and are in regular medical follow‐up in these HIV centres. Patients will be monitored for Leishmania infection and VL for a period of up to three years with three‐monthly clinical and laboratory evaluation. In addition, the immunoprofile of the different types/stages of Leishmania infection and the associated risk profiles will be determined.
Based on this information, we aim to develop and evaluate prognostic clinical tools, integrating host, HIV and Leishmania infection markers, to detect individuals at high risk of VL. Ultimately, this could lead to a
“screen and treat” strategy for VL in HIV‐infected individuals living in VL‐endemic areas. HIV has been identified as one of the emerging challenges for control of visceral leishmaniasis (VL). This problem is now especially severe in Ethiopia – a L. donovani endemic region ‐ where up to 40% of patients with VL are co‐infected with HIV. Once VL is established in HIV‐infected individuals‐ meaning that L donovani infection has evolved to the disease stage ‐ prognosis at the individual level is dire, with high rates of case fatality (reaching 25%), treatment failure (up to 50%) and relapse (up to 60%). Tackling Leishmania infection before disease onset would thus be a logical approach.
Increasingly, it has been recognized that asymptomatic infections outnumber VL cases in most regions.
Although not fully understood, the outcome of Leishmania infection (ranging from parasite clearance to VL) is thought to be largely determined by immunological factors. This has however never been studied in depth on a background of HIV immune suppression. Importantly, in striking contrast with immunocompetent individuals where the risk of disease progression after infection is relatively low, and treatment of asymptomatic cases is currently not recommended, the situation might be entirely different in HIV‐coinfected, immunosuppressed individuals. We hypothesize that the period of asymptomatic Leishmania infection constitutes a window of opportunity for screening strategies, to capture those at high risk of VL. However, the basic understanding and evidence underpinning such a screening approach is currently lacking.
We propose to conduct a multi‐centre prospective cohort study including HIV‐positive adults enrolled in HIV care in a VL endemic region in North‐Ethiopia. Since 2009 we have established a clinical research network in this region that provides a unique platform for studying the clinical aspects of asymptomatic Leishmania infection and exploring a screening approach. Within the study area, we have identified two HIV clinical cohorts, with a total of over 3000 HIV‐infected patients in follow‐up. As residents of this region with high VL‐endemicity, they are exposed to Leishmania donovani infection and are in regular medical follow‐up in these HIV centres. Patients will be monitored for Leishmania infection and VL for a period of up to three years with three‐monthly clinical and laboratory evaluation. In addition, the immunoprofile of the different types/stages of Leishmania infection and the associated risk profiles will be determined.
Based on this information, we aim to develop and evaluate prognostic clinical tools, integrating host, HIV and Leishmania infection markers, to detect individuals at high risk of VL. Ultimately, this could lead to a
“screen and treat” strategy for VL in HIV‐infected individuals living in VL‐endemic areas.
adults resident in a VL endemic region in Ethiopia
- To describe the relationship between different Leishmania infection markers and how this evolves over time
- To estimate the short‐term risk and determinants of VL disease progression after Leishmania infection and the impact on HIV‐1 infection markers
- To determine the immune‐profile of different types/stages of Leishmania infection and the associated risk profiles (staging and prognostic markers)

Project type:PhD project