The increasing incidence of visceral leishmaniasis relapse in South Sudan: A retrospective analysis of field patient data from 2001-2018.

backgroundVisceral Leishmaniasis (VL) is endemic in South Sudan, manifesting periodically in major outbreaks. Provision of treatment during endemic periods and as an emergency response is impeded by instability and conflict. Médecins Sans Frontières (MSF) has provided health care in South Sudan since the late 1980's, including treatment for 67,000 VL patients. In recent years, MSF monitoring data have indicated increasing numbers of VL relapse cases. A retrospective analysis of these data was performed in order to provide insight into the possible causes of this increase. METHODOLOGY/PRINCIPAL

findingsProgramme monitoring data from the MSF hospital in Lankien, Jonglei State, South Sudan, for the period 2001-2018 were analysed to detect trends in VL relapse as a proportion of all VL cases presenting to MSF treatment centres. Routinely collected patient-level data from relapse and primary VL cases treated at all MSF sites in South Sudan over the same period were analysed to describe patient characteristics and treatments received. VL relapse as a proportion of all VL cases increased by 6.5% per annum (95% CI 0.3% to 13.0%, p = 0.04), from 5.2% during 2001-2003 to 14.4% during 2016-2018. Primary VL and VL relapse patients had similar age, sex and anthropometric characteristics, the latter indicating high indices of undernutrition which were relatively constant over time. Clinical factors (Hb, spleen size, and VL severity score) also did not vary substantially over time. SSG/PM was the main treatment regimen from 2001-2018, used in 68.7% of primary and 70.9% of relapse VL cases; AmBisome was introduced in 2013, received by 22.5% of primary VL and 32.6% of VL relapse cases from 2013-2018.

conclusionIncreasing incidence of VL relapse in South Sudan does not appear to be explained by changes in patient characteristics or other factors. Our data are concerning and may indicate an emergence of treatment-resistant parasite strains, decreasing the effectiveness of treatment regimens. This warrants further investigation as a causal factor. New chemical entities that will enable safe and highly effective short-course oral treatments for VL are urgently needed.