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

Léon Mbiyangandu Kazumba, Jean Claude Tshinzobe Kaka, Dieudonné Mumba Ngoyi, Daniel Tshala-Katumbay

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0006504
JournalPLoS Neglected Tropical Diseases
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

African Trypanosomiasis
Democratic Republic of the Congo
Melarsoprol
Eflornithine
Mortality
Appointments and Schedules
Nifurtimox
Logistic Models
Therapeutics
Trypanosomiasis
Body Fluids
Neurology
Parasites
Retrospective Studies
Odds Ratio
Recurrence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

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. / Kazumba, Léon Mbiyangandu; Kaka, Jean Claude Tshinzobe; Ngoyi, Dieudonné Mumba; Tshala-Katumbay, Daniel.

In: PLoS Neglected Tropical Diseases, Vol. 12, No. 6, e0006504, 01.06.2018.

Research output: Contribution to journalArticle

@article{9608c4322188406cb6c15a87317dfa15,
title = "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",
abstract = "We conducted a retrospective study on mortality trends and risk factors in 781 na{\"i}ve 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 = "Kazumba, {L{\'e}on Mbiyangandu} and Kaka, {Jean Claude Tshinzobe} and Ngoyi, {Dieudonn{\'e} Mumba} and Daniel Tshala-Katumbay",
year = "2018",
month = "6",
day = "1",
doi = "10.1371/journal.pntd.0006504",
language = "English (US)",
volume = "12",
journal = "PLoS Neglected Tropical Diseases",
issn = "1935-2727",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Mortality trends and risk factors in advanced stage-2 Human African Trypanosomiasis

T2 - A critical appraisal of 23 years of experience in the Democratic Republic of Congo

AU - Kazumba, Léon Mbiyangandu

AU - Kaka, Jean Claude Tshinzobe

AU - Ngoyi, Dieudonné Mumba

AU - Tshala-Katumbay, Daniel

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85049376319&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049376319&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0006504

DO - 10.1371/journal.pntd.0006504

M3 - Article

C2 - 29897919

AN - SCOPUS:85049376319

VL - 12

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

SN - 1935-2727

IS - 6

M1 - e0006504

ER -