Mortality trends and risk factors in advanced stage-2 Human African Trypanosomiasis: A critical appraisal of 23 years of experience in the Democratic Republic of Congo

We conducted a retrospective study on mortality trends and risk factors in 781 naïve cases of advanced stage-2 sleeping sickness admitted between 1989 and 2012 at the National Reference Center for Human African Trypanosomiasis (HAT), Department of Neurology, Kinshasa University, Democratic Republic of Congo (DRC). Death was the outcome variable whereas age, gender, duration of disease, location of trypanosomes in body fluids, cytorachy, protidorachy, clinical status (assessed on a syndromic and functional basis) on admission, and treatment regimen were predictors in logistic regression models run at the 0.05 significance level. Death proportions were 17.2% in the standard melarsoprol schedule (3-series of intravenous melarsoprol on 3 successive days at 3.6 mg/kg/d, with a one-week interval between the series, ARS 9); 12.1% in the short schedule melarsoprol (10 consecutive days of intravenous melarsoprol at 2.2 mg/kg/d, ARS 10), 5.4% in the first-line eflornithine (14 days of eflornithine at 400 mg/kg/d in 4 infusions a day DFMO B), 9.1% in the NECT treatment regimen (eflornithine for 7 days at 400, mg/kg/d in 2 infusions a day combined with oral nifurtimox for 10 days at 15 mg/kg/d in 3 doses a day); and high (36%) in the group with select severely affected patients given eflornithine because of their clinical status on admission, at the time when this expensive drug was kept for treatment of relapses (14 days at 400 mg/kg/d in 4 infusions a day, DFMO A). After adjusting for treatment, death odds ratios were as follows: 10.40 [(95% CI: 6.55–16.51); p = .000] for clinical dysfunction (severely impaired clinical status) on admission, 2.14 [(95% CI: 1.35–3.39); p = .001] for high protidorachy, 1.99 [(95% CI: 1.18–3.37); p = .010] for the presence of parasites in the CSF and 1.70 [(95% CI: 1.03–2.81); p = .038] for high cytorachy. A multivariable analysis within treatment groups retained clinical status on admission (in ARS 9, ARS 10 and DFMO B groups) and high protidorachy (in ARS 10 and DFMO B groups) as significant predictors of death. The algorithm for initial clinical status assessment used in the present study may serve as the basis for further development of standardized assessment tools relevant to the clinical management of HAT and information exchange in epidemiological reports.Author summary: This study reports on the importance of recording data related to the clinical presentation on admission in sleeping sickness. We collected data on 781 second-stage patients admitted in the Trypanosomiasis Unit of the Department of Neurology of the University of Kinshasa from 1989 to 2012. The following information were registered: age, sex, symptomatology duration, trypanosome parasites location in body fluids, clinical presentation on admission, cerebrospinal fluid (CSF) cell count, CSF protein concentration, therapeutic regimen, and post-treatment outcome in terms of death or survival. Analyses demonstrated that the most influential factor on the occurrence of death was a dysfunctional clinical status on admission (reflecting advanced disease). These results support the idea that the algorithm used to categorize patients in the present work can be proposed for validation in prospective studies with the purpose of designing a standardized clinical procedure assessing disease severity and bearing predictive value of outcome.