scholarly journals Modelling the impact of fexinidazole use on human African trypanosomiasis (HAT) transmission in the Democratic Republic of the Congo

2021 ◽  
Vol 15 (11) ◽  
pp. e0009992
Author(s):  
Aatreyee M. Das ◽  
Nakul Chitnis ◽  
Christian Burri ◽  
Daniel H. Paris ◽  
Swati Patel ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Lumbar Puncture ◽  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
Oral Treatment ◽  
World Health ◽  
Disease Stage ◽  
African Trypanosomiasis ◽  
Republic Of The Congo ◽  
Stage 1

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to care.

scholarly journals Modelling the impact of fexinidazole use on human African trypanosomiasis (HAT) transmission in the Democratic Republic of the Congo

2021 ◽  
Author(s):  
Aatreyee Mimi Das ◽  
Nakul Chitnis ◽  
Christian Burri ◽  
Daniel H. Paris ◽  
Swati Patel ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Lumbar Puncture ◽  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
Oral Treatment ◽  
World Health ◽  
Disease Stage ◽  
African Trypanosomiasis ◽  
Republic Of The Congo ◽  
Stage 1

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis, and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to passive care.

scholarly journals New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story

2020 ◽  
Vol 5 (1) ◽  
pp. 29 ◽  
Author(s):  
Emily A. Dickie ◽  
Federica Giordani ◽  
Matthew K. Gould ◽  
Pascal Mäser ◽  
Christian Burri ◽  
...  
Keyword(s):  
Oral Therapy ◽  
Human African Trypanosomiasis ◽  
First Century ◽  
New Drugs ◽  
World Health ◽  
African Trypanosomiasis ◽  
Twenty First Century ◽  
Health Organization ◽  
Stage 1 ◽  
Competing Priorities

The twentieth century ended with human African trypanosomiasis (HAT) epidemics raging across many parts of Africa. Resistance to existing drugs was emerging, and many programs aiming to contain the disease had ground to a halt, given previous success against HAT and the competing priorities associated with other medical crises ravaging the continent. A series of dedicated interventions and the introduction of innovative routes to develop drugs, involving Product Development Partnerships, has led to a dramatic turnaround in the fight against HAT caused by Trypanosoma brucei gambiense. The World Health Organization have been able to optimize the use of existing tools to monitor and intervene in the disease. A promising new oral medication for stage 1 HAT, pafuramidine maleate, ultimately failed due to unforeseen toxicity issues. However, the clinical trials for this compound demonstrated the possibility of conducting such trials in the resource-poor settings of rural Africa. The Drugs for Neglected Disease initiative (DNDi), founded in 2003, has developed the first all oral therapy for both stage 1 and stage 2 HAT in fexinidazole. DNDi has also brought forward another oral therapy, acoziborole, potentially capable of curing both stage 1 and stage 2 disease in a single dosing. In this review article, we describe the remarkable successes in combating HAT through the twenty first century, bringing the prospect of the elimination of this disease into sight.

scholarly journals Quantifying epidemiological drivers of gambiense human African Trypanosomiasis across the Democratic Republic of Congo

2020 ◽  
Author(s):  
Ronald E Crump ◽  
Ching-I Huang ◽  
Ed Knock ◽  
Simon E F Spencer ◽  
Paul Brown ◽  
...  
Keyword(s):  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
Democratic Republic Of Congo ◽  
Model Fitting ◽  
Case Finding ◽  
World Health ◽  
Model Parameters ◽  
African Trypanosomiasis ◽  
Republic Of Congo ◽  
Case Data

AbstractGambiense human African trypanosomiasis (gHAT) is a virulent disease declining in burden but still endemic in West and Central Africa. Although it is targeted for elimination of transmission by 2030, there remain numerous questions about the drivers of infection and how these vary geographically.In this study we focus on the Democratic Republic of Congo (DRC), which accounted for 84% of the global case burden in 2016, to explore changes in transmission across the country and elucidate factors which may have contributed to the persistence of disease or success of interventions in different regions. We present a Bayesian fitting methodology, applied to 168 endemic health zones (∼ 100,000 population size), which allows for calibration of mechanistic gHAT model to case data (from the World Health Organization HAT Atlas) in an adaptive and automated framework.It was found that the model needed to capture improvements in passive detection to match observed trends in the data within former Bandundu and Bas Congo provinces indicating these regions have substantially reduced time to detection. Health zones in these provinces generally had longer burn-in periods during fitting due to additional model parameters.Posterior probability distributions were found for a range of fitted parameters in each health zone; these included the basic reproduction number estimates for pre-1998 (R0) which was inferred to be between 1 and 1.19, in line with previous gHAT estimates, with higher median values typically in health zones with more case reporting in the 2000s.Previously, it was not clear whether a fall in active case finding in the period contributed to the declining case numbers. The modelling here accounts for variable screening and suggests that underlying transmission has also reduced greatly – on average 96% in former Equateur, 93% in former Bas Congo and 89% in former Bandundu – Equateur and Bandundu having had the highest case burdens in 2000. This analysis also sets out a framework to enable future predictions for the country.Author summaryGambiense human African trypanosomiasis (gHAT; sleeping sickness) is a deadly disease targeted for elimination by 2030, however there are still several unknowns about what factors influence continued transmission and how this changes with geographic location.In this study we focus on the Democratic Republic of Congo (DRC), which reported 84% of the global cases in 2016 to try and explain why some regions of the country have had more success than others in bringing down case burden. To achieve this we used a state-of-the-art statistical framework to match a mathematical gHAT model to reported case data for 168 regions with some case reporting during 2000–2016.The analysis indicates that two former provinces, Bandundu and Bas Congo had substantial improvements to case detection in fixed health facilities in the time period. Overall, all provinces were estimated to have reductions in (unobservable) transmission including ∼ 96% in former Equateur. This is reassuring as case finding effort has decreased in that region.The model fitting presented here will allow predictions of gHAT under future strategies to be performed in the future.

scholarly journals Human African trypanosomiasis in the Democratic Republic of the Congo: disease distribution and risk

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Crispin Lumbala ◽  
Pere P. Simarro ◽  
Giuliano Cecchi ◽  
Massimo Paone ◽  
José R. Franco ◽  
...  
Keyword(s):  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
African Trypanosomiasis ◽  
Republic Of The Congo

scholarly journals Human African Trypanosomiasis in the Democratic Republic of the Congo: A Looming Emergency?

2012 ◽  
Vol 6 (12) ◽  
pp. e1950 ◽  
Author(s):  
Epco Hasker ◽  
Pascal Lutumba ◽  
François Chappuis ◽  
Victor Kande ◽  
Julien Potet ◽  
...  
Keyword(s):  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
African Trypanosomiasis ◽  
Republic Of The Congo

scholarly journals SNPs in IL4 and IFNG show no protective associations with human African trypanosomiasis in the Democratic Republic of the Congo: a case-control study

2020 ◽  
Vol 3 ◽  
pp. 35
Author(s):  
Olivier Fataki Asina ◽  
Harry Noyes ◽  
Bruno Bucheton ◽  
Hamidou Ilboudo ◽  
Annette MacLeod ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
Latent Infection ◽  
Service Providers ◽  
Tsetse Flies ◽  
Nucleotide Polymorphisms ◽  
Latent Infections ◽  
African Trypanosomiasis ◽  
Republic Of The Congo

Background: Human African trypanosomiasis (HAT) is a protozoal disease transmitted by tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self-cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, polymorphisms in 17 candidate genes were tested (APOL1 [G1 and G2], CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF, TNFA, IL6, IL4, IL8, IFNG, and HLA-G). Methods: Samples were collected in Democratic Republic of the Congo. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Commercial service providers genotyped polymorphisms at 96 single nucleotide polymorphisms (SNPs) on 17 genes. Data were analyzed using Plink V1.9 software and R. Loci, with suggestive associations (uncorrected p < 0.05) validated using an additional 594 individuals, including 164 cases and 430 controls. Results: After quality control, 87 SNPs remained in the analysis. Two SNPs in IL4 and two in IFNG were suggestively associated (uncorrected p<0.05) with a differential risk of developing a Trypanosoma brucei gambiense infection in the Congolese population. The IFNG minor allele (rs2430561, rs2069718) SNPs were protective in comparison between latent infections and controls. Carriers of the rs2243258_T and rs2243279_A alleles of IL4 and the rs2069728_T allele of IFNG had a reduced risk of developing illness or latent infection, respectively. None of these associations were significant after Bonferroni correction for multiple testing. A validation study using more samples was run to determine if the absence of significant association was due to lack of power. Conclusions: This study showed no evidence of an association of HAT with IL4 and IFNG SNPs or with APOL1 G1 and G2 alleles, which have been found to be protective in other studies.

scholarly journals Feasibility of a dried blood spot strategy for serological screening and surveillance to monitor elimination of Human African Trypanosomiasis in the Democratic Republic of the Congo

2021 ◽  
Vol 15 (6) ◽  
pp. e0009407
Author(s):  
Raquel Inocencio da Luz ◽  
Delphin Mavinga Phanzu ◽  
Oscar N’lemvo Kiabanzawoko ◽  
Eric Miaka ◽  
Paul Verlé ◽  
...  
Keyword(s):  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
Dried Blood Spot ◽  
Screening Tests ◽  
African Trypanosomiasis ◽  
Screening And Surveillance ◽  
Elisa Testing ◽  
Two Samples ◽  
Republic Of The Congo ◽  
Blood Spot

In recent years, the number of reported Human African Trypanosomiasis (HAT) cases caused by Trypanosoma brucei (T.b.) gambiense has been markedly declining, and the goal of ‘elimination as a public health problem’ is within reach. For the next stage, i.e. interruption of HAT transmission by 2030, intensive screening and surveillance will need to be maintained, but with tools and strategies more efficiently tailored to the very low prevalence. We assessed the sequential use of ELISA and Immune Trypanolysis (ITL) on dried blood spot (DBS) samples as an alternative to the traditional HAT field testing and confirmation approach. A cross-sectional study was conducted in HAT endemic and previously endemic zones in Kongo Central province, and a non-endemic zone in Haut Katanga province in the Democratic Republic of the Congo (DRC). Door-to-door visits were performed to collect dried blood spot (DBS) samples on filter paper. ELISA/T.b. gambiense was conducted followed by ITL for those testing positive by ELISA and in a subset of ELISA negatives. In total, 11,642 participants were enrolled. Of these, 11,535 DBS were collected and stored in appropriate condition for ELISA testing. Ninety-seven DBS samples tested positive on ELISA. In the endemic zone, ELISA positivity was 1.34% (95%CI: 1.04–1.64). In the previously endemic zone and non-endemic zone, ELISA positivity was 0.34% (95% CI: 0.13–0.55) and 0.37% (95% CI: 0.15–0.60) respectively. Among the ELISA positives, only two samples had a positive ITL result, both from the endemic zone. One of those was from a former HAT patient treated in 2008 and the other from an individual who unfortunately had deceased prior to the follow-up visit. Our study showed that a surveillance strategy, based on DBS samples and centralized testing with retracing of patients if needed, is feasible in DRC. ELISA seems well suited as initial test with a similar positivity rate as traditional screening tests, but ITL remains complex. Alternatives for the latter, also analyzable on DBS, should be further explored.

scholarly journals Quantifying epidemiological drivers of gambiense human African Trypanosomiasis across the Democratic Republic of Congo

2021 ◽  
Vol 17 (1) ◽  
pp. e1008532
Author(s):  
Ronald E. Crump ◽  
Ching-I Huang ◽  
Edward S. Knock ◽  
Simon E. F. Spencer ◽  
Paul E. Brown ◽  
...  
Keyword(s):  
Human African Trypanosomiasis ◽  
Democratic Republic ◽  
Democratic Republic Of Congo ◽  
Probability Distributions ◽  
Central Africa ◽  
World Health ◽  
Model Parameters ◽  
African Trypanosomiasis ◽  
Republic Of Congo ◽  
Variable Screening

Gambiense human African trypanosomiasis (gHAT) is a virulent disease declining in burden but still endemic in West and Central Africa. Although it is targeted for elimination of transmission by 2030, there remain numerous questions about the drivers of infection and how these vary geographically. In this study we focus on the Democratic Republic of Congo (DRC), which accounted for 84% of the global case burden in 2016, to explore changes in transmission across the country and elucidate factors which may have contributed to the persistence of disease or success of interventions in different regions. We present a Bayesian fitting methodology, applied to 168 endemic health zones (∼100,000 population size), which allows for calibration of a mechanistic gHAT model to case data (from the World Health Organization HAT Atlas) in an adaptive and automated framework. It was found that the model needed to capture improvements in passive detection to match observed trends in the data within former Bandundu and Bas Congo provinces indicating these regions have substantially reduced time to detection. Health zones in these provinces generally had longer burn-in periods during fitting due to additional model parameters. Posterior probability distributions were found for a range of fitted parameters in each health zone; these included the basic reproduction number estimates for pre-1998 (R0) which was inferred to be between 1 and 1.14, in line with previous gHAT estimates, with higher median values typically in health zones with more case reporting in the 2000s. Previously, it was not clear whether a fall in active case finding in the period contributed to the declining case numbers. The modelling here accounts for variable screening and suggests that underlying transmission has also reduced greatly—on average 96% in former Equateur, 93% in former Bas Congo and 89% in former Bandundu—Equateur and Bandundu having had the highest case burdens in 2000. This analysis also sets out a framework to enable future predictions for the country.

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