Journal Article > ResearchFull Text
Am J Trop Med Hyg. 2013 November 11; Volume 90 (Issue 1); DOI:10.4269/ajtmh.13-0150
Mueller YK, Kolaczinski JH, Koech T, Lokwang P, Riongoita M, et al.
Am J Trop Med Hyg. 2013 November 11; Volume 90 (Issue 1); DOI:10.4269/ajtmh.13-0150
Between 2000 and 2010, Médecins Sans Frontières diagnosed and treated 4,831 patients with visceral leishmaniasis (VL) in the Pokot region straddling the border between Uganda and Kenya. A retrospective analysis of routinely collected clinical data showed no marked seasonal or annual fluctuations. Males between 5 and 14 years of age were the most affected group. Marked splenomegaly and anemia were striking features. An Rk39 antigen-based rapid diagnostic test was evaluated and found sufficiently accurate to replace the direct agglutination test and spleen aspiration as the first-line diagnostic procedure. The case-fatality rate with sodium stibogluconate as first-line treatment was low. The VL relapses were rare and often diagnosed more than 6 months post-treatment. Post-kala-azar dermal leishmaniasis was rare but likely to be underdiagnosed. The epidemiological and clinical features of VL in the Pokot area differed markedly from VL in Sudan, the main endemic focus in Africa.
Journal Article > ResearchFull Text
Acta Trop. 2007 January 1; Volume 101 (Issue 1); DOI:10.1016/j.actatropica.2006.12.002
Eperon G, Schmid C, Loutan L, Chappuis F
Acta Trop. 2007 January 1; Volume 101 (Issue 1); DOI:10.1016/j.actatropica.2006.12.002
BACKGROUND: Existing data on human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense among children are limited. Here, we described the demographic, clinical, diagnostic, treatment and outcome characteristics of HAT in pre-school children from Kajo-Keji County, South Sudan in comparison with older patients. METHODS: We did a retrospective analysis of HAT patients treated at the Kiri Sleeping Sickness Treatment Centre (SSTC), Kajo-Keji County, from June 2000 to December 2002. RESULTS: Of 1958 HAT patients, 119 (6.1%) were pre-school children (<6 years) including 56 (47%) in first-stage illness and 63 (53%) in second-stage. The proportion of children in second-stage HAT was significantly higher in very young children (<2 years). Walking and speech disturbances were more frequent in second-stage HAT but other neurological symptoms and signs were not associated with disease stage. Pentamidine treatment for first-stage illness was very safe and effective among pre-school children. In contrast, 4.9% of pre-school children in second-stage illness died during melarsoprol treatment and 46% had > or = 1 severe adverse event(s). Macular rash, jaundice and skin necrosis on injection site were significantly more frequent in this age group (p<0.05). Melarsoprol-induced encephalopatic syndrome was less frequent but more severe than in older age groups. CONCLUSION: The clinical features of T. b. gambiense HAT among pre-school children are insufficiently stage-specific. Therefore, laboratory-based staging is mandatory to prevent unnecessary harm to HAT patients caused by the high toxicity of melarsoprol.
Journal Article > ResearchFull Text
J Infect Dis. 2005 June 1; Volume 191 (Issue 11); DOI:10.1086/429929
Schmid C, Richer M, Bilenge CM, Josenando T, Chappuis F, et al.
J Infect Dis. 2005 June 1; Volume 191 (Issue 11); DOI:10.1086/429929
BACKGROUND: Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study. METHODS: A total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up. RESULTS: The cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively. CONCLUSIONS: The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense.
Journal Article > ResearchFull Text
Trans R Soc Trop Med Hyg. 2008 October 21; Volume 103 (Issue 3); DOI:10.1016/j.trstmh.2008.09.005
Balasegaram M, Young H, Chappuis F, Priotto G, Raguenaud ME, et al.
Trans R Soc Trop Med Hyg. 2008 October 21; Volume 103 (Issue 3); DOI:10.1016/j.trstmh.2008.09.005
This paper describes the effectiveness of first-line regimens for stage 2 human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense infection in nine Médecins Sans Frontières HAT treatment programmes in Angola, Republic of Congo, Sudan and Uganda. Regimens included eflornithine and standard- and short-course melarsoprol. Outcomes for 10461 naïve stage 2 patients fitting a standardised case definition and allocated to one of the above regimens were analysed by intention-to-treat analysis. Effectiveness was quantified by the case fatality rate (CFR) during treatment, the proportion probably and definitely cured and the Kaplan-Meier probability of relapse-free survival at 12 months and 24 months post admission. The CFR was similar for the standard- and short-course melarsoprol regimens (4.9% and 4.2%, respectively). The CFR for eflornithine was 1.2%. Kaplan-Meier survival probabilities varied from 71.4-91.8% at 1 year and 56.5-87.9% at 2 years for standard-course melarsoprol, to 73.0-91.1% at 1 year for short-course melarsoprol, and 79.9-97.4% at 1 year and 68.6-93.7% at 2 years for eflornithine. With the exception of one programme, survival at 12 months was >90% for eflornithine, whilst for melarsoprol it was <90% except in two sites. Eflornithine is recommended where feasible, especially in areas with low melarsoprol effectiveness.
Journal Article > ResearchFull Text
Ann Trop Med Parasitol. 2008 January 1; Volume 102 (Issue 1); DOI:10.1179/136485908X252142
Mueller YK, Nguimfack A, Cavailler P, Couffignal S, Rwakimari JB, et al.
Ann Trop Med Parasitol. 2008 January 1; Volume 102 (Issue 1); DOI:10.1179/136485908X252142
Between September 2003 and April 2004, the supply of antimonial drugs to Amudat Hospital, in north-eastern Uganda, was interrupted and all cases of visceral leishmaniasis presenting at the hospital could only be treated with amphotericin B deoxycholate (AmB). This allowed the safety and effectiveness of the AmB to be evaluated, in comparison with an historical cohort of patients treated, at the same hospital, with meglumine antimoniate (Sb(V)). Demographic and clinical data were collected before and after treatment. Adverse effects were recorded passively in all the subjects, and actively, using a standardized questionnaire, in a sub-group of the patients given AmB. The in hospital case-fatality 'rates' were 4.8% [95% confidence interval (CI) = 2.4%-8.8%] among the 210 patients treated with AmB and 3.7% (CI = 1.4%-7.9%) among the 161 patients treated with Sb(V) (P>0.20). Adverse effects requiring treatment interruption were rare in both cohorts. Treatment failures (i.e. non-responses or relapses) were observed in 2.9% (CI = 1.2%-6.4%) of the patients treated with AmB and 1.2% (CI = 0.1%-4.4%) of the patients treated with Sb(V) (P>0.20). For the treatment of visceral leishmaniasis in Uganda, AmB therefore had a similar effectiveness and safety profile to that of meglumine antimoniate.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 2004 September 1; Volume 71 (Issue 3); 313-317.
Chappuis F, Stivanello E, Adams K, Kidane S, Pittet A, et al.
Am J Trop Med Hyg. 2004 September 1; Volume 71 (Issue 3); 313-317.
The diagnosis of human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense relies on an initial serologic screening with the card agglutination test for trypanosomiasis (CATT) for T. b. gambiense, followed by parasitologic confirmation in most endemic areas. Unfortunately, field parasitologic methods lack sensitivity and the management of serologically suspected individuals (i.e., individuals with a positive CATT result but negative parasitology) remains controversial. In Kajo-Keji County in southern Sudan, we prospectively collected sociodemographic and laboratory data of a cohort of 2,274 serologically suspected individuals. Thirty-three percent (n = 749) attended at least one follow-up visit and HAT was confirmed in 64 (9%) cases. Individuals with lower initial CATT-plasma (CATT-P) end-dilution titers had lowest risks (10.4 and 13.8/100 person-years for 1:4 and 1:8 titers, respectively) that significantly increased for higher dilutions: relative risks = 5.1 (95% confidence interval [CI] = 2.6-9.5) and 4.6 (95% CI = 2.8-9.8) for 1:16 and 1:32 titers, respectively. The cumulative yearly risk was also high (76%) in individuals found with 11-20 cells in the cerebrospinal fluid, but this involved only eight patients. Adjustment for potential confounders did not affect the results. In conclusion, treatment with pentamidine should be considered for all serologically suspected individuals with a CATT-P end-dilution titer >/= 1:16 in areas of a moderate to high prevalence of HAT.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2021 February 12; Volume 15 (Issue 2); e0009023.; DOI:10.1371/journal.pntd.0009023
Alcoba G, Ochoa C, Martins SB, Ruiz de Castañeda R, Bolon I, et al.
PLoS Negl Trop Dis. 2021 February 12; Volume 15 (Issue 2); e0009023.; DOI:10.1371/journal.pntd.0009023
BACKGROUND
Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.
METHODOLOGY/PRINCIPAL FINDINGS
We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.
CONCLUSIONS/SIGNIFICANCE
This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.
Worldwide, it is estimated that snakes bite 4.5-5.4 million people annually, 2.7 million of which are envenomed, and 81,000-138,000 die. The World Health Organization reported these estimates and recognized the scarcity of large-scale, community-based, epidemiological data. In this context, we developed the "Snake-Byte" project that aims at (i) quantifying and mapping the impact of snakebite on human and animal health, and on livelihoods, (ii) developing predictive models for medical, ecological and economic indicators, and (iii) analyzing geographic accessibility to healthcare. This paper exclusively describes the methodology we developed to collect large-scale primary data on snakebite in humans and animals in two hyper-endemic countries, Cameroon and Nepal.
METHODOLOGY/PRINCIPAL FINDINGS
We compared available methods on snakebite epidemiology and on multi-cluster survey development. Then, in line with those findings, we developed an original study methodology based on a multi-cluster random survey, enhanced by geospatial, One Health, and health economics components. Using a minimum hypothesized snakebite national incidence of 100/100,000/year and optimizing design effect, confidence level, and non-response margin, we calculated a sample of 61,000 people per country. This represented 11,700 households in Cameroon and 13,800 in Nepal. The random selection with probability proportional to size generated 250 clusters from all Cameroonian regions and all Nepalese Terai districts. Our household selection methodology combined spatial randomization and selection via high-resolution satellite images. After ethical approval in Switerland (CCER), Nepal (BPKIHS), and Cameroon (CNERSH), and informed written consent, our e-questionnaires included geolocated baseline demographic and socio-economic characteristics, snakebite clinical features and outcomes, healthcare expenditure, animal ownership, animal outcomes, snake identification, and service accessibility.
CONCLUSIONS/SIGNIFICANCE
This novel transdisciplinary survey methodology was subsequently used to collect countrywide snakebite envenoming data in Nepal and Cameroon. District-level incidence data should help health authorities to channel antivenom and healthcare allocation. This methodology, or parts thereof, could be easily adapted to other countries and to other Neglected Tropical Diseases.
Journal Article > ResearchFull Text
Lancet. 2018 July 12; Volume 392 (Issue 10148); DOI:10.1016/S0140-6736(18)31224-8
Longbottom J, Shearer FM, Devine M, Alcoba G, Chappuis F, et al.
Lancet. 2018 July 12; Volume 392 (Issue 10148); DOI:10.1016/S0140-6736(18)31224-8
Snakebite envenoming is a frequently overlooked cause of mortality and morbidity. Data for snake ecology and existing snakebite interventions are scarce, limiting accurate burden estimation initiatives. Low global awareness stunts new interventions, adequate health resources, and available health care. Therefore, we aimed to synthesise currently available data to identify the most vulnerable populations at risk of snakebite, and where additional data to manage this global problem are needed.
Journal Article > ResearchFull Text
Clin Microbiol Rev. 2005 January 1; Volume 18 (Issue 1); DOI:10.1128/CMR.18.1.133-146.2005
Chappuis F, Loutan L, Simarro P, Lejon V, Bu¨scher P
Clin Microbiol Rev. 2005 January 1; Volume 18 (Issue 1); DOI:10.1128/CMR.18.1.133-146.2005
Human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense or T. b. rhodesiense remains highly prevalent in several rural areas of sub-Saharan Africa and is lethal if left untreated. Therefore, accurate tools are absolutely required for field diagnosis. For T. b. gambiense HAT, highly sensitive tests are available for serological screening but the sensitivity of parasitological confirmatory tests remains insufficient and needs to be improved. Screening for T. b. rhodesiense infection still relies on clinical features in the absence of serological tests available for field use. Ongoing research is opening perspectives for a new generation of field diagnostics. Also essential for both forms of HAT is accurate determination of the disease stage because of the high toxicity of melarsoprol, the drug most widely used during the neurological stage of the illness. Recent studies have confirmed the high accuracy of raised immunoglobulin M levels in the cerebrospinal fluid for the staging of T. b. gambiense HAT, and a promising simple assay (LATEX/IgM) is being tested in the field. Apart from the urgent need for better tools for the field diagnosis of this neglected disease, improved access to diagnosis and treatment for the population at risk remains the greatest challenge for the coming years.
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.