Dataset Information

Predicting the Impact of Intervention Strategies for Sleeping Sickness in Two High-Endemicity Health Zones of the Democratic Republic of Congo.

ABSTRACT: Two goals have been set for Gambian human African trypanosomiasis (HAT), the first is to achieve elimination as a public health problem in 90% of foci by 2020, and the second is to achieve zero transmission globally by 2030. It remains unclear if certain HAT hotspots could achieve elimination as a public health problem by 2020 and, of greater concern, it appears that current interventions to control HAT in these areas may not be sufficient to achieve zero transmission by 2030. A mathematical model of disease dynamics was used to assess the potential impact of changing the intervention strategy in two high-endemicity health zones of Kwilu province, Democratic Republic of Congo. Six key strategies and twelve variations were considered which covered a range of recruitment strategies for screening and vector control. It was found that effectiveness of HAT screening could be improved by increasing effort to recruit high-risk groups for screening. Furthermore, seven proposed strategies which included vector control were predicted to be sufficient to achieve an incidence of less than 1 reported case per 10,000 people by 2020 in the study region. All vector control strategies simulated reduced transmission enough to meet the 2030 goal, even if vector control was only moderately effective (60% tsetse population reduction). At this level of control the full elimination threshold was expected to be met within six years following the start of the change in strategy and over 6000 additional cases would be averted between 2017 and 2030 compared to current screening alone. It is recommended that a two-pronged strategy including both enhanced active screening and tsetse control is implemented in this region and in other persistent HAT foci to ensure the success of the control programme and meet the 2030 elimination goal for HAT.

SUBMITTER: Rock KS

PROVIDER: S-EPMC5215767 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Predicting the Impact of Intervention Strategies for Sleeping Sickness in Two High-Endemicity Health Zones of the Democratic Republic of Congo.

Rock Kat S KS Torr Steve J SJ Lumbala Crispin C Keeling Matt J MJ

PLoS neglected tropical diseases 20170105 1

Two goals have been set for Gambian human African trypanosomiasis (HAT), the first is to achieve elimination as a public health problem in 90% of foci by 2020, and the second is to achieve zero transmission globally by 2030. It remains unclear if certain HAT hotspots could achieve elimination as a public health problem by 2020 and, of greater concern, it appears that current interventions to control HAT in these areas may not be sufficient to achieve zero transmission by 2030. A mathematical mod ...[more]

PMID: 28056016

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Project description:BackgroundSleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans.MethodsUsing modelling, we explore how cryptic (undetected) transmission impacts the monitoring of progress towards and the achievement of the EoT goal. We have developed gHAT models that include either asymptomatic or animal transmission, and compare these to a baseline gHAT model without either of these transmission routes, to explore the potential role of cryptic infections on the EoT goal. Each model was independently calibrated to five different health zones in the Democratic Republic of the Congo (DRC) using available historical human case data for 2000-2020 (obtained from the World Health Organization's HAT Atlas). We applied a novel Bayesian sequential updating approach for the asymptomatic model to enable us to combine statistical information about this type of transmission from each health zone.ResultsOur results suggest that, when matched to past case data, we estimated similar numbers of new human infections between model variants, although human infections were slightly higher in the models with cryptic infections. We simulated the continuation of screen-confirm-and-treat interventions, and found that forward projections from the animal and asymptomatic transmission models produced lower probabilities of EoT than the baseline model; however, cryptic infections did not prevent EoT from being achieved eventually under this approach.ConclusionsThis study is the first to simulate an (as-yet-to-be available) screen-and-treat strategy and found that removing a parasitological confirmation step was predicted to have a more noticeable benefit to transmission reduction under the asymptomatic model compared with the others. Our simulations suggest vector control could greatly impact all transmission routes in all models, although this resource-intensive intervention should be carefully prioritised.

Project description:BackgroundNifurtimox-eflornithine combination therapy (NECT) for the treatment of second stage gambiense human African trypanosomiasis (HAT) was added to the World Health Organization's Essential Medicines List in 2009 after demonstration of its non-inferior efficacy compared to eflornithine therapy. A study of NECT use in the field showed acceptable safety and high efficacy until hospital discharge in a wide population, including children, pregnant and breastfeeding women, and patients with a HAT treatment history. We present here the effectiveness results after the 24-month follow-up visit.Methodology/principal findingsIn a multicenter, open label, single arm phase IIIb study, second stage gambiense HAT patients were treated with NECT in the Democratic Republic of Congo. Clinical cure was defined 24 months after treatment as survival without clinical and/or parasitological signs of HAT. Of the 629 included patients, 619 (98.4%) were discharged alive after treatment and were examined for the presence of trypanosomes, white blood cell count in cerebro-spinal fluid, and disease symptoms. The clinical cure rate of 94.1% was comparable for all subpopulations analyzed at the 24-month follow-up visit. Self-reported adverse events during follow-up were few and concerned mainly nervous system disorders, infections, and gastro-intestinal disorders. Overall, 28 patients (4.3%) died during the course of the trial. The death of 16 of the 18 patients who died during the follow-up period was assessed as unlikely or not related to NECT. Within 24 months, eight patients (1.3%) relapsed and received rescue treatment. Sixteen patients were completely lost to follow-up.Conclusions/significanceNECT treatment administered under field conditions was effective and sufficiently well tolerated, no major concern arose for children or pregnant or breastfeeding women. Patients with a previous HAT treatment history had the same response as those who were naïve. In conclusion, NECT was confirmed as effective and appropriate for use in a broad population, including vulnerable subpopulations.Trial registrationThe trial is registered at ClinicalTrials.gov, number NCT00906880.

Project description:BackgroundNifurtimox eflornithine combination therapy (NECT) to treat human African trypanosomiasis (HAT), commonly called sleeping sickness, was added to the World Health Organisation's (WHO) Essential Medicines List in 2009 and to the Paediatric List in 2012. NECT was further tested and documented in a phase IIIb clinical trial in the Democratic Republic of Congo (DRC) assessing the safety, effectiveness, and feasibility of implementation under field conditions (NECT-FIELD study). This trial brought a unique possibility to examine concomitant drug management.Methodology/principal findingsThis is a secondary analysis of the NECT-FIELD study where 629 second stage gambiense HAT patients were treated with NECT, including children and pregnant and breastfeeding women in six general reference hospitals located in two provinces. Concomitant drugs were prescribed by the local investigators as needed. Patients underwent daily evaluations, including vital signs, physical examination, and adverse event monitoring. Concomitant medication was documented from admission to discharge. Patients' clinical profiles on admission and safety profile during specific HAT treatment were similar to previously published reports. Prescribed concomitant medications administered during the hospitalization period, before, during, and immediately after NECT treatment, were mainly analgesics/antipyretics, anthelmintics, antimalarials, antiemetics, and sedatives. Use of antibiotics was reasonable and antibiotics were often prescribed to treat cellulitis and respiratory tract infections. Prevention and treatment of neurological conditions such as convulsions, loss of consciousness, and coma was used in approximately 5% of patients.Conclusions/significanceThe prescription of concomitant treatments was coherent with the clinical and safety profile of the patients. However, some prescription habits would need to be adapted in the future to the evolving available pharmacopoeia. A list of minimal essential medication that should be available at no cost to patients in treatment wards is proposed to help the different actors to plan, manage, and adequately fund drug supplies for advanced HAT infected patients.Trial registration numberThe initial study was registered at ClinicalTrials.gov, number NCT00906880.

Dataset Information

Predicting the Impact of Intervention Strategies for Sleeping Sickness in Two High-Endemicity Health Zones of the Democratic Republic of Congo.

Publications

Predicting the Impact of Intervention Strategies for Sleeping Sickness in Two High-Endemicity Health Zones of the Democratic Republic of Congo.

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