Journal Article > ResearchFull Text
Trop Med Int Health. 2004 August 1; Volume 9 (Issue 8); DOI:10.1111/j.1365-3156.2004.01266.x
Robays J, Ebeja Kadima A, Lutumba P, Miaka mia Bilenge C, Kande Betu Ku Mesu V, et al.
Trop Med Int Health. 2004 August 1; Volume 9 (Issue 8); DOI:10.1111/j.1365-3156.2004.01266.x
BACKGROUND: Increasing numbers of human African trypanosomiasis (HAT) cases have been reported in urban residents of Kinshasa, Democratic Republic Congo since 1996. We set up a case-control study to identify risk factors for the disease. METHODS: All residents of the urban part of Kinshasa with parasitologically confirmed HAT and presenting for treatment to the city's specialized HAT clinics between 1 August, 2002 and 28 February, 2003 were included as cases. We defined the urban part as the area with contiguous habitation and a population density >5000 inhabitants per square kilometre. A digital map of the area was drawn based on a satellite image. For each case, two serologically negative controls were selected, matched on age, sex and neighbourhood. Logistic regression models were fitted to control for confounding. RESULTS: The following risk factors were independently associated with HAT: travel, commerce and cultivating fields in Bandundu, and commerce and cultivating fields in the rural part of Kinshasa. No association with activities in the city itself was found. DISCUSSION: In 2002, the emergence of HAT in urban residents of Kinshasa appears mainly linked to disease transmission in Bandundu and rural Kinshasa. We recommend to intensify control of these foci, to target HAT screening in urban residents to people with contact with these foci, to increase awareness of HAT amongst health workers in the urban health structures and to strengthen disease surveillance.
Journal Article > Short ReportFull Text
BMC Research Notes. 2015 July 4; Volume 8 (Issue 292); DOI:10.1186/s13104-015-1244-3
Checchi F, Funk S, Chandramohan D, Haydon DT, Chappuis F
BMC Research Notes. 2015 July 4; Volume 8 (Issue 292); DOI:10.1186/s13104-015-1244-3
BACKGROUND
The duration of the stages of HAT is an important factor in epidemiological studies and intervention planning. Previously, we published estimates of the duration of the haemo-lymphatic stage 1 and meningo-encephalitic stage 2 of the gambiense form of human African trypanosomiasis (HAT), in the absence of treatment. Here we revise the estimate of stage 2 duration, computed based on data from Uganda and South Sudan, by adjusting observed infection prevalence for incomplete case detection coverage and diagnostic inaccuracy.
FINDINGS
The revised best estimate for the mean duration of stage 2 is 252 days (95% CI 171-399), about half of our initial best estimate, giving a total mean duration of untreated gambiense HAT infection of approximately 2 years and 2 months.
CONCLUSIONS
Our new estimate provides improved information on the transmission dynamics of this neglected tropical disease in Uganda and South Sudan. We stress that there remains considerable variability around the estimated mean values, and that one must be cautious in applying these results to other foci.
The duration of the stages of HAT is an important factor in epidemiological studies and intervention planning. Previously, we published estimates of the duration of the haemo-lymphatic stage 1 and meningo-encephalitic stage 2 of the gambiense form of human African trypanosomiasis (HAT), in the absence of treatment. Here we revise the estimate of stage 2 duration, computed based on data from Uganda and South Sudan, by adjusting observed infection prevalence for incomplete case detection coverage and diagnostic inaccuracy.
FINDINGS
The revised best estimate for the mean duration of stage 2 is 252 days (95% CI 171-399), about half of our initial best estimate, giving a total mean duration of untreated gambiense HAT infection of approximately 2 years and 2 months.
CONCLUSIONS
Our new estimate provides improved information on the transmission dynamics of this neglected tropical disease in Uganda and South Sudan. We stress that there remains considerable variability around the estimated mean values, and that one must be cautious in applying these results to other foci.
Conference Material > Slide Presentation
Beko P, Woudenberg T
MSF Scientific Days International 2020: Research. 2020 May 13
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2012 November 29; Volume 6 (Issue 11); DOI:10.1371/journal.pntd.0001920
Schmid C, Kuemmerle A, Blum J, Ghabri S, Kande V, et al.
PLoS Negl Trop Dis. 2012 November 29; Volume 6 (Issue 11); DOI:10.1371/journal.pntd.0001920
Trypanosoma brucei (T.b.) gambiense Human African trypanosomiasis (HAT; sleeping sickness) is a fatal disease. Until 2009, available treatments for 2(nd) stage HAT were complicated to use, expensive (eflornithine monotherapy), or toxic, and insufficiently effective in certain areas (melarsoprol). Recently, nifurtimox-eflornithine combination therapy (NECT) demonstrated good safety and efficacy in a randomised controlled trial (RCT) and was added to the World Health Organisation (WHO) essential medicines list (EML). Documentation of its safety profile in field conditions will support its wider use.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2016 February 16; Volume 10 (Issue 2); e0004362.; DOI:10.1371/journal.pntd.0004362
Burri C, Yeramian PD, Allen JL, Merolle A, Serge KK, et al.
PLoS Negl Trop Dis. 2016 February 16; Volume 10 (Issue 2); e0004362.; DOI:10.1371/journal.pntd.0004362
BACKGROUND
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.
METHODS
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.
FINDINGS/CONCLUSION
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.
AUTHOR SUMMARY
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by parasites, and has a chronic progressive course that may last from several months to several years before death occurs. The present studies were done to assess the effectiveness and safety of oral pafuramidine versus intramuscular pentamidine (the standard treatment), in patients with first stage HAT. The results indicated that, several months after treatment, pafuramidine administered for 10 days was as effective as pentamidine administered for 7 days, and it had a better safety profile than pentamidine. With further study, pafuramidine could be a promising alternative for patients with first stage HAT. In addition, the design of the studies can be used a guide for future studies for identification and delivery of treatment to affected individuals in rural Africa.
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.
METHODS
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.
FINDINGS/CONCLUSION
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.
AUTHOR SUMMARY
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by parasites, and has a chronic progressive course that may last from several months to several years before death occurs. The present studies were done to assess the effectiveness and safety of oral pafuramidine versus intramuscular pentamidine (the standard treatment), in patients with first stage HAT. The results indicated that, several months after treatment, pafuramidine administered for 10 days was as effective as pentamidine administered for 7 days, and it had a better safety profile than pentamidine. With further study, pafuramidine could be a promising alternative for patients with first stage HAT. In addition, the design of the studies can be used a guide for future studies for identification and delivery of treatment to affected individuals in rural Africa.
Conference Material > Video
Beko P, Woudenberg T
MSF Scientific Days International 2020: Research. 2020 May 26
Journal Article > EditorialFull Text
Pathogens. 2023 October 19; Volume 12 (Issue 10); 1263.; DOI:10.3390/pathogens12101263
Santos ALS, Rodrigues IA, d’Avila-Levy CM, Sodré CL, Ritmeijer KKD, et al.
Pathogens. 2023 October 19; Volume 12 (Issue 10); 1263.; DOI:10.3390/pathogens12101263
Human African trypanosomiasis (also known as sleeping sickness, with Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense as etiological agents), American trypanosomiasis (also known as Chagas disease, with Trypanosoma cruzi as the etiological agent), and leishmaniasis (including cutaneous, mucocutaneous, and visceral forms, with multiple species belonging to the Leishmania genus as etiological agents) are recognized as neglected tropical diseases (NTDs). These diseases affect marginalized populations and pose a high-impact health problem, primarily in low- or low-to-middle-income countries in Africa, Asia, Latin America, and the Caribbean. Leishmania and Trypanosoma not only infect humans, but they also infect wild and domesticated animals, which serve as reservoirs for these diseases. Relevantly, the movement of people and animals across borders and within countries has become increasingly common in our interconnected world, and this mobility can both facilitate the transmission of diseases and challenge efforts to control outbreaks. Furthermore, climate changes can contribute to the spread of NTDs to areas that were previously unaffected.
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 2012 December 13; Volume 6 (Issue 12); DOI:10.1371/journal.pntd.0001950
Hasker E, Lutumba P, Chappuis F, Kande V, Potet J, et al.
PLoS Negl Trop Dis. 2012 December 13; Volume 6 (Issue 12); DOI:10.1371/journal.pntd.0001950
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 2010 May 25; Volume 4 (Issue 5); DOI:10.1371/journal.pntd.0000720
Yun O, Priotto G, Tong J, Flevaud L, Chappuis F
PLoS Negl Trop Dis. 2010 May 25; Volume 4 (Issue 5); DOI:10.1371/journal.pntd.0000720
Journal Article > Meta-AnalysisFull Text
Confl Health. 2011 May 26; Volume 5 (Issue 1); DOI:10.1186/1752-1505-5-7
Tong J, Valverde O, Mahoudeau C, Yun O, Chappuis F
Confl Health. 2011 May 26; Volume 5 (Issue 1); DOI:10.1186/1752-1505-5-7
Human African trypanosomiasis (HAT), or sleeping sickness, is a fatal neglected tropical disease if left untreated. HAT primarily affects people living in rural sub-Saharan Africa, often in regions afflicted by violent conflict. Screening and treatment of HAT is complex and resource-intensive, and especially difficult in insecure, resource-constrained settings. The country with the highest endemicity of HAT is the Democratic Republic of Congo (DRC), which has a number of foci of high disease prevalence. We present here the challenges of carrying out HAT control programmes in general and in a conflict-affected region of DRC. We discuss the difficulties of measuring disease burden, medical care complexities, waning international support, and research and development barriers for HAT.