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

Abstract

Background Visceral 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 findings Programme 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. Conclusion Increasing 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.

Estimating the proportion of relapse following treatment of Visceral Leishmaniasis: meta-analysis using Infectious Diseases Data Observatory (IDDO) systematic review

“…Furthermore, a recent retrospective analysis of data from routine care by Médecins Sans Frontières in South Sudan characterised that over 15% of all relapses occurred after one year. 27 This is important for disease control and elimination since identification and prompt treatment of cases is critical for reducing the infective pool of parasites that can sustain the disease transmission. Therefore, the findings of this meta-analysis taken together with existing literature 4 , 5 , 6 , 26 suggests that a longer follow-up duration is warranted in VL studies.…”

Host, parasite and drug determinants of clinical outcomes following treatment of visceral leishmaniasis: a protocol for individual participant data meta-analysis

“…As the overall incidence of VL is falling, a growing proportion of the total reported cases in the region is attributed to relapses 44. A recent report from South Sudan has also indicated increasing incidence of relapses over the past two decades 45. This is an important public health concern as patients with relapse are predisposed to further relapse, especially among those with HIV coinfections 12.…”

“…44 A recent report from South Sudan has also indicated increasing incidence of relapses over the past two decades. 45 This is an important public health concern as patients with relapse are predisposed to further relapse, especially among those with HIV coinfections. 12 Increasingly large proportion of VL patients has been found to present with HIV coinfections in Brazil (0.7% in 2001 to 8.5% in 2012), India (0.88% in 2000 to 4.19% in 2020) and Northern Ethiopia (15%–35%).…”

Prognostic prediction models for clinical outcomes in patients diagnosed with visceral leishmaniasis: protocol for a systematic review

“…Prognostic prediction models (referred henceforth as prognostic models) play a central role in VL risk stratification; informing healthcare providers, policymakers and patients on the treatment setting, treatment regimen and intensity of follow-up. [7][8][9] Systematic reviews of prognostic models have been published across a range of infectious diseases, [10][11][12] serving not only to inform healthcare providers on available risk stratification tools, but also as a research tool to identify candidate models for external validation or updating (recalibration) with data from new settings. Indeed, the lack of external validation studies is considered the greatest barrier to the broader acceptance of prognostic models as a reliable and acceptable clinical tool.…”