Longitudinal evaluation of asymptomatic Leishmania infection in HIV-infected individuals in North-West Ethiopia: A pilot study

Abstract

Background

In endemic regions, asymptomatic Leishmania infection is common. In HIV patients, detection of asymptomatic Leishmania infection could potentially identify those at risk of visceral leishmaniasis (VL). However, data on the prevalence, incidence, and determinants of asymptomatic infection, and the risk of VL are lacking.

Methods

We conducted a cross-sectional survey at a single ART centre, followed by a prospective cohort study amongst HIV-infected adults in HIV care in a district hospital in a VL-endemic area in North-West Ethiopia (9/2015-8/2016). Asymptomatic Leishmania infection was detected using the direct agglutination test (DAT), rK39-rapid diagnostic test (RDT)), PCR on peripheral blood and the KAtex urine antigen test, and defined as positivity on any Leishmania marker. All individuals were followed longitudinally (irrespective of the Leishmania test results). Risk factors for asymptomatic Leishmania infection were determined using logistic regression.

Results

A total of 534 HIV-infected individuals enrolled in HIV care were included in the study. After excluding 13 patients with a history of VL and an 10 patients with incomplete baseline Leishmania tests, 511 were included in analysis. The median age was 38 years (interquartile range (IQR) 30–45), 62.6% were male. The median follow-up time was 12 months (IQR 9–12). No deaths were reported during the study period. Most (95.5%) were on antiretroviral treatment at enrolment, for a median of 52 months (IQR 27–79). The median CD4 count at enrolment was 377 cells/mm3 (IQR 250–518). The baseline prevalence of Leishmania infection was 12.8% in males and 4.2% in females. Overall, 7.4% tested positive for rK39, 4.3% for DAT, 0.2% for PCR and 0.2% for KAtex. Independent risk factors for a prevalent infection were male sex (odds ratio (OR) 3.2; 95% confidence intervals (CI) 14–7.0) and concurrent malaria infection (OR 6.1; 95% CI 1.9–18.9). Amongst the 49 prevalent (baseline) infections with further follow-up, the cumulative incidence of losing the Leishmania markers by one year was 40.1%. There were 36 incident infections during the course of the study, with a cumulative one-year risk of 9.5%. Only one case of VL was detected during follow-up.

Conclusions

We found a high prevalence of asymptomatic Leishmania infection, persisting in most cases. The incidence was more modest and overt VL was rare. Larger and longer studies with more complete follow-up may help to decide whether a test and treat strategy would be justified in this context.

Trial registration

ClinicalTrials.gov NCT02839603

Author summary

As visceral leishmaniasis (VL) in HIV patients is difficult to treat and associated with high mortality, strategies to detect and treat asymptomatic Leishmania infection in HIV patients should be explored. However, data on the prevalence, incidence, determinants of asymptomatic infection and risk of VL are lacking. We conducted a longitudinal study, including HIV-infected adult patients in HIV care in a district hospital in a VL-endemic area in North-West Ethiopia. Asymptomatic Leishmania infection was evaluated by Leishmania antibody tests (DAT and rK39), urine antigen tests (KAtex) and PCR, and was defined as positivity on any Leishmania marker. We also looked for independent risk factors for asymptomatic Leishmania infection at study recruitment. A total of 511 patients were included in the analysis. The median age was 38 years, 62.6% were male. The median time of residence in a VL-endemic area was 18 years. Most (95.5%) were on antiretroviral treatment at enrolment, for a median of 52 months. The median CD4 count at enrolment was 377 cells/mm ³. The baseline prevalence of Leishmania infection was 12.8% in males and 4.2% in females. Overall, 7.4% tested positive for rK39, 4.3% for DAT, 0.2% for PCR and 0.2% for KAtex. Independent risk factors for a prevalent infection were male sex and concurrent malaria infection. Amongst the 49 prevalent infections that were present upon enrolment in the study, the probability of losing the Leishmania markers by one year was 40.1%. There were 36 new infections during the course of the study, with an overall risk of 9.5% by one year of follow-up. One case of VL was detected during follow-up. In conclusion, we found a high prevalence of asymptomatic Leishmania infection, which persisted in most cases. The incidence was more modest. Larger and longer studies would be needed to decide whether a test and treat strategy would be justified in this context.