Now showing items 21-40 of 42

    • Estimates of the duration of the early and late stage of gambiense sleeping sickness.

      Checchi, F; Filipe, J A N; Haydon, D T; Chandramohan, D; Chappuis, F; Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E7HT, UK. francesco.checchi@lshtm.ac.uk (BioMed Central, 2008-02-08)
      BACKGROUND: The durations of untreated stage 1 (early stage, haemo-lymphatic) and stage 2 (late stage, meningo-encephalitic) human African trypanosomiasis (sleeping sickness) due to Trypanosoma brucei gambiense are poorly quantified, but key to predicting the impact of screening on transmission. Here, we outline a method to estimate these parameters. METHODS: We first model the duration of stage 1 through survival analysis of untreated serological suspects detected during Médecins Sans Frontières interventions in Uganda and Sudan. We then deduce the duration of stage 2 based on the stage 1 to stage 2 ratio observed during active case detection in villages within the same sites. RESULTS: Survival in stage 1 appears to decay exponentially (daily rate = 0.0019; mean stage 1 duration = 526 days [95%CI 357 to 833]), possibly explaining past reports of abnormally long duration. Assuming epidemiological equilibrium, we estimate a similar duration of stage 2 (500 days [95%CI 345 to 769]), for a total of nearly three years in the absence of treatment. CONCLUSION: Robust estimates of these basic epidemiological parameters are essential to formulating a quantitative understanding of sleeping sickness dynamics, and will facilitate the evaluation of different possible control strategies.
    • Eflornithine is a cost-effective alternative to melarsoprol for the treatment of second-stage human West African trypanosomiasis in Caxito, Angola.

      Robays, J; Raguenaud, M E; Josenando, T; Boelaert, M; Institute of Tropical Medicine, Antwerp, Belgium. Medecins Sans Frontieres Belgium. National Sleeping Sickness control program of Angola (2008-02)
      OBJECTIVE: To compare the cost-effectiveness of eflornithine and melarsoprol in the treatment of human African trypanosomiasis. METHOD: We used data from a Médecins Sans Frontières treatment project in Caxito, Angola to do a formal cost-effectiveness analysis, comparing the efficiency of an eflornithine-based approach with melarsoprol. Endpoints calculated were: cost per death avoided; incremental cost per additional life saved; cost per years of life lost (YLL) averted; incremental cost per YLL averted. Sensitivity analysis was done for all parameters for which uncertainty existed over the plausible range. We did an analysis with and without cost of trypanocidal drugs included. RESULTS: Effectiveness was 95.6% for melarsoprol and 98.7% for eflornithine. Cost/patient was 504.6 for melarsoprol and 552.3 for eflornithine, cost per life saved was 527.5 USD for melarsoprol and 559.8 USD for eflornithine without cost of trypanocidal drugs but it increases to 600.4 USD and 844.6 USD per patient saved and 627.6 USD and 856.1 USD per life saved when cost of trypanocidal drugs are included. Incremental cost-effectiveness ratio is 1596 USD per additional life saved and 58 USD per additional life year saved in the baseline scenario without cost of trypanocidal drugs but it increases to 8169 USD per additional life saved and 299 USD per additional life year saved if costs of trypanocidal drugs are included. CONCLUSION: Eflornithine saves more lives than melarsoprol, but melarsoprol is slightly more cost-effective. Switching from melarsoprol to eflornithine can be considered as a cost-effective option according to the WHO choice criteria.
    • Nifurtimox-eflornithine Combination Therapy for Second-Stage Trypanosoma Brucei Gambiense Sleeping Sickness: A Randomized Clinical Trial in Congo.

      Priotto, G; Kasparian, S; Ngouama, D; Ghorashian, S; Arnold, U; Ghabri, S; Karunakara, U; Epicentre, Paris, France. gpriotto@epicentre.msf.org (Published by: Infectious Diseases Society of America, 2007-12-01)
      BACKGROUND: Human African trypanosomiasis caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are either highly toxic or impracticable in field conditions. We compared the efficacy and safety of the nifurtimox-eflornithine drug combination with the standard eflornithine regimen for the treatment of second-stage disease. METHODS: A randomized, open-label, active-control, phase III clinical trial comparing 2 arms was conducted at the Sleeping Sickness Treatment Center, which was run by Medecins Sans Frontieres, in Nkayi, Bouenza Province, Republic of Congo. Patients were screened for inclusion and randomly assigned to receive eflornithine alone (400 mg/kg per day given intravenously every 6 h for 14 days) or eflornithine (400 mg/kg per day given intravenously every 12 h for 7 days) plus nifurtimox (15 mg/kg per day given orally every 8 h for 10 days). Patients were observed for 18 months. The study's outcomes were cure and adverse events attributable to treatment. RESULTS: A total of 103 patients with second-stage disease were enrolled. Cure rates were 94.1% for the eflornithine group and 96.2% for the nifurtimox-eflornithine group. Drug reactions were frequent in both arms, and severe reactions affected 25.5% of patients in the eflornithine group and 9.6% of those in the nifurtimox-eflornithine group, resulting in 2 and 1 treatment suspensions, respectively. There was 1 death in the eflornithine arm and no deaths in the nifurtimox-eflornithine arm. CONCLUSIONS: The nifurtimox-eflornithine combination appears to be a promising first-line therapy for second-stage sleeping sickness. If our findings are corroborated by ongoing findings from additional sites (a multicenter extension of this study), the new nifurtimox-eflornithine combination therapy will mark a major and multifaceted advance over current therapies.
    • Melarsoprol-Free Drug Combinations for Second-Stage Gambian Sleeping Sickness: The Way to Go.

      Chappuis, F; Travel and Migration Medicine Unit, Geneva University Hospital, and Medecins Sans Frontieres, Swiss Section, 1202 Geneva, Switzerland. francois.chappuis@hcuge.ch (Published by: Infectious Diseases Society of America, 2007-12-01)
    • Nifurtimox plus Eflornithine for Late-Stage Sleeping Sickness in Uganda: A Case Series.

      Checchi, F; Piola, P; Ayikoru, H; Thomas, F; Legros, D; Priotto, G; Epicentre, Paris, France. (Public Library of Science, 2007)
      BACKGROUND: We report efficacy and safety outcomes from a prospective case series of 31 late-stage T.b. gambiense sleeping sickness (Human African Trypanosomiasis, HAT) patients treated with a combination of nifurtimox and eflornithine (N+E) in Yumbe, northwest Uganda in 2002-2003, following on a previously reported terminated trial in nearby Omugo, in which 17 patients received the combination under the same conditions. METHODOLOGY/PRINCIPAL FINDINGS: Eligible sequential late-stage patients received 400 mg/Kg/day eflornithine (Ornidyl, Sanofi-Aventis) for seven days plus 15 mg/Kg/day (20 mg for children <15 years old) nifurtimox (Lampit, Bayer AG) for ten days. Efficacy (primary outcome) was monitored for 24 months post discharge. Clinical and laboratory adverse events (secondary outcome) were monitored during treatment. All 31 patients were discharged alive, but two died post-discharge of non-HAT and non-treatment causes, and one was lost to follow-up. Efficacy ranged from 90.3% to 100.0% according to analysis approach. Five patients experienced major adverse events during treatment, and neutropenia was common (9/31 patients). CONCLUSIONS/SIGNIFICANCE: Combined with the previous group of 17 trial patients, this case series yields a group of 48 patients treated with N+E, among whom no deaths judged to be treatment- or HAT-related, no treatment terminations and no relapses have been noted, a very favourable outcome in the context of late-stage disease. N+E could be the most promising combination regimen available for sleeping sickness, and deserves further evaluation.
    • Clinical Presentation and Treatment Outcome of Sleeping Sickness in Sudanese Pre-School Children.

      Eperon, G; Schmid, C; Loutan, L; Chappuis, F; Médecins Sans Frontières, Rue de Lausanne 78, 1202 Geneva, Switzerland. (2007-01)
      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.
    • Melarsoprol Versus Eflornithine for Treating Late-stage Gambian Trypanosomiasis in the Republic of the Congo.

      Balasegaram, M; Harris, S; Checchi, F; Ghorashian, S; Hamel, C; Karunakara, U; Medecins Sans Frontieres, London, England. manica.balasigaram@london.msf.org (Published by WHO, 2006-10)
      OBJECTIVE: To compare the effectiveness of melarsoprol and eflornithine in treating late-stage Gambian trypanosomiasis in the Republic of the Congo. METHODS: We analysed the outcomes of death during treatment and relapse within 1 year of discharge for 288 patients treated with eflornithine, 311 patients treated with the standard melarsoprol regimen and 62 patients treated with a short-course (10-day) melarsoprol regimen between April 2001 and April 2005. FINDINGS: A total of 1.7% (5/288) of patients treated with eflornithine died compared with 4.8% (15/311) of those treated with standard melarsoprol and 6.5% (4/62) of those treated with short-course melarsoprol. Patients treated with eflornithine tended to be younger and were more likely to have trypanosomes or higher white blood cell counts in their cerebrospinal fluid. The cumulated incidence of relapse among patients who attended at least one follow-up visit 1 year after discharge was 8.1% (11/136) for those treated with eflornithine, 14% (36/258) for those treated with standard melarsoprol and 15.5% (9/58) for those treated with shortcourse melarsoprol. In a multivariate analysis, when compared with eflornithine, standard melarsoprol was found to be a risk factor for both death (odds ratio (OR) = 2.87; 95% confidence interval (CI) = 1.03-8.00) and relapse (hazard ratio (HR) = 2.47; 95% CI = 1.22-5.03); when compared with eflornithine, short-course melarsoprol was also found to be a risk factor for death (OR = 3.90; 95% CI = 1.02-14.98) and relapse (HR = 6.65; 95% CI = 2.61-16.94). CONCLUSION: The effectiveness of melarsoprol treatment appears to have diminished. Eflornithine seems to be a better first-line therapy for treating late-stage Gambian trypanosomiasis in the Republic of the Congo.
    • Treatment Outcomes and Risk Factors for Relapse in Patients with Early-stage Human African Trypanosomiasis (HAT) in the Republic of the Congo.

      Balasegaram, M; Harris, S; Checchi, F; Hamel, C; Karunakara, U; Medecins Sans Frontieres, London, England. manica.balasigaram@london.msf.org (Published by WHO, 2006-10)
      OBJECTIVE: In 2002-03, the Republic of the Congo increased the threshold separating stage 1 and 2 cases of human African trypanosomiasis (HAT) from a cerebrospinal fluid (CSF) white cell count of 5 cells/mm(3) to 10 cells/mm(3). We aimed to assess whether the increased threshold of 10 cells/mm(3) is a safe indicator of stage 2 disease. METHODS: We assessed patients treated for stage 1 HAT caused by Trypanosoma brucei gambiense in the Republic of the Congo between April 2001 and April 2005. Patients with 0-10 cells/mm(3) in CSF were classed as stage 1 and treated with pentamidine. Patients with CSF of > 10 cells/mm(3) were classed as stage 2 and treated with either melarsoprol or eflornithine. We did a retrospective analysis of all patients treated after the September 2002 increase in threshold for classification of HAT disease stage 2, and who were eligible for at least 1 year of follow-up. Primary outcome was survival without death or relapse within 1 year of discharge. Risk factors for treatment failure, in particular CSF white cell count on diagnosis, were assessed. FINDINGS: Between September 2002 to April 2004, 692 patients eligible for our analysis were treated with pentamidine. All were discharged alive. Relapse rate was 5% (n = 33). The only identified risk factor for relapse was a CSF white cell count of 6-10 cells/mm(3) rather than 0-5 cells/mm(3) (adjusted hazard ratio 3.27 (95% confidence interval, 1.52-7.01); P = 0.002). CONCLUSION: A threshold of 5 white cells/mm(3) in CSF is safer than 10 cells/mm(3) to determine stage 2 HAT and reduce risk of relapse.
    • Three drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda.

      Priotto, G; Fogg, C; Balasegaram, M; Erphas, O; Louga, A; Checchi, F; Ghabri, S; Piola, P; gpriotto@epicentre.msf.org (2006)
      OBJECTIVES: Our objective was to compare the efficacy and safety of three drug combinations for the treatment of late-stage human African trypanosomiasis caused by Trypanosoma brucei gambiense. DESIGN: This trial was a randomized, open-label, active control, parallel clinical trial comparing three arms. SETTING: The study took place at the Sleeping Sickness Treatment Center run by Médecins Sans Frontières at Omugo, Arua District, Uganda PARTICIPANTS: Stage 2 patients diagnosed in Northern Uganda were screened for inclusion and a total of 54 selected. INTERVENTIONS: Three drug combinations were given to randomly assigned patients: melarsoprol-nifurtimox (M+N), melarsoprol-eflornithine (M+E), and nifurtimox-eflornithine (N+E). Dosages were uniform: intravenous (IV) melarsoprol 1.8 mg/kg/d, daily for 10 d; IV eflornithine 400 mg/kg/d, every 6 h for 7 d; oral nifurtimox 15 (adults) or 20 (children <15 y) mg/kg/d, every 8 h for 10 d. Patients were followed up for 24 mo. OUTCOME MEASURES: Outcomes were cure rates and adverse events attributable to treatment. RESULTS: Randomization was performed on 54 patients before enrollment was suspended due to unacceptable toxicity in one of the three arms. Cure rates obtained with the intention to treat analysis were M+N 44.4%, M+E 78.9%, and N+E 94.1%, and were significantly higher with N+E (p = 0.003) and M+E (p = 0.045) than with M+N. Adverse events were less frequent and less severe with N+E, resulting in fewer treatment interruptions and no fatalities. Four patients died who were taking melarsoprol-nifurtimox and one who was taking melarsoprol-eflornithine. CONCLUSIONS: The N+E combination appears to be a promising first-line therapy that may improve treatment of sleeping sickness, although the results from this interrupted study do not permit conclusive interpretations. Larger studies are needed to continue the evaluation of this drug combination in the treatment of T. b. gambiense sleeping sickness.
    • Eflornithine is Safer Than Melarsoprol for the Treatment of Second-Stage Trypanosoma Brucei Gambiense Human African Trypanosomiasis.

      Chappuis, F; Udayraj, N; Stietenroth, K; Meussen, A; Bovier, P A; Médecins Sans Frontières, Geneva University Hospitals, Geneva, Switzerland. francois.chappuis@hcuge.ch (Published by: Infectious Diseases Society of America, 2005-09-01)
      Patients with second-stage human African trypanosomiasis treated with eflornithine (n = 251) in 2003 in Kiri, southern Sudan, had an adjusted relative risk of death of 0.2 and experienced significantly fewer cutaneous and neurological adverse effects than did patients who were treated with melarsoprol in 2001 and 2002 (n = 708).
    • Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II).

      Schmid, C; Richer, M; Bilenge, C M M; Josenando, T; Chappuis, F; Manthelot, C R; Nangouma, A; Doua, F; Asumu, P; Simarro, P; et al. (Infectious Diseases Society of America and University of Chicago Press, 2005-06-01)
      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.
    • Options for field diagnosis of human african trypanosomiasis.

      Chappuis, F; Loutan, L; Simarro, P; Lejon, V; Büscher, P; Travel and Migration Medicine Unit, Geneva University Hospital, 24 rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. francois.chappuis@hcuge.ch (The American Society for Microbiology, 2005-01)
      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.
    • Card Agglutination Test for Trypanosomiasis (CATT) End-Dilution Titer and Cerebrospinal Fluid Cell Count as Predictors of Human African Trypanosomiasis (Trypanosoma brucei gambiense) Among Serologically Suspected Individuals in Southern Sudan.

      Chappuis, F; Stivanello, E; Adams, K; Kidane, S; Pittet, A; Bovier, P A; Médecins Sans Frontières, Swiss Section, Geneva, Switzerland. francois.chappuis@hcuge.ch (Published by: American Society of Tropical Medicine and Hygiene, 2004-09)
      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.
    • Human African trypanosomiasis amongst urban residents in Kinshasa: a case-control study.

      Robays, J; Ebeja, A; Lutumba, P; Miaka mia Bilenge, C; Kande Betu Ku Mesu, V; De Deken, R; Makabuza, J; Deguerry, M; Van der Stuyft, P; Boelaert, M; et al. (2004-08)
      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.
    • Trypanosoma Brucei Gambiense Trypanosomiasis in Terego County, Northern Uganda, 1996: A Lot Quality Assurance Sampling Survey.

      Hutin, Y; Legros, D; Owini, V; Brown, V; Lee, E; Mbulamberi, D; Paquet, C; Epicentre Office in Uganda, Kampala, Uganda. (Published by: American Society of Tropical Medicine and Hygiene, 2004-04)
      We estimated the pre-intervention prevalence of Trypanosoma brucei gambiense (Tbg) trypanosomiasis using the lot quality assurance sampling (LQAS) methods in 14 parishes of Terego County in northern Uganda. A total of 826 participants were included in the survey sample in 1996. The prevalence of laboratory confirmed Tbg trypanosomiasis adjusted for parish population sizes was 2.2% (95% confidence interval =1.1-3.2). This estimate was consistent with the 1.1% period prevalence calculated on the basis of cases identified through passive and active screening in 1996-1999. Ranking of parishes in four categories according to LQAS analysis of the 1996 survey predicted the prevalences observed during the first round of active screening in the population in 1997-1998 (P < 0.0001, by chi-square test). Overall prevalence and ranking of parishes obtained with LQAS were validated by the results of the population screening, suggesting that these survey methods may be useful in the pre-intervention phase of sleeping sickness control programs.
    • Sleeping sickness in the region of the town of Kinshasa: a retrospective analysis during the surveillance period 1996-2000.

      Ebeja, A; Lutumba, P; Molisho, D; Kegels, G; Miaka mia Bilenge, C; Boelaert, M; Médecins sans Frontières, Kinshasa, République Démocratique du Congo. kadima_ebeja@hotmail.com (Wiley-Blackwell, 2003-10)
      In the Democratic Republic of Congo, the re-emergence of sleeping sickness is no longer limited to rural areas. Over the course of the past decade, more and more cases have been reported from urban centres such as Kinshasa, Mbuji-mayi, Matadi and Boma. This paper presents a retrospective analysis on the region of Kinshasa over the period 1996-2000, using epidemiological surveillance, individual case files and available entomological data. There are 22 health districts in total; they were classified as urban when the population exceeded 5000 per square kilometre. The Human African Trypanosomiasis (HAT) control programme reported 2451 parasitologically confirmed new cases between 1996 and 2000, in the entire region of Kinshasa. Affected people (66%) were aged 15-49 years. Cases occurred in every health district, and 956 (39%) occurred in urban residents. Glossina captures in 1999 established the presence of Trypanosoma spp. Local HAT transmission is plausible but not proven. The high number of urban cases necessitates development of control strategies adapted to cities.
    • Field evaluation of the CATT/Trypanosoma brucei gambiense on blood-impregnated filter papers for diagnosis of human African trypanosomiasis in southern Sudan.

      Chappuis, F; Pittet, A; Bovier, P A; Adams, K; Godineau, V; Hwang, S Y; Magnus, E; Büscher, P; Médecins Sans Frontières (MSF) - Switzerland, Geneva, Switzerland. francois.chappuis@hcuge.ch (Wiley-Blackwell, 2002-11)
      Most Human African Trypanosomiasis (HAT) control programmes in areas endemic for Trypanosoma brucei gambiense rely on a strategy of active mass screening with the Card Agglutination Test for Trypanosomiasis (CATT)/T. b. gambiense. We evaluated the performance, stability and reproducibility of the CATT/T. b. gambiense on blood-impregnated filter papers (CATT-FP) in Kajo-Keji County, South-Sudan, where some areas are inaccessible to mobile teams. The CATT-FP was performed with a group of 100 people with a positive CATT on whole blood including 17 confirmed HAT patients and the results were compared with the CATT on plasma (CATT-P). The CATT-FP was repeated on impregnated filter papers stored at ambient and refrigerated temperature for 1, 3, 7 and 14 days. Another 82 patients with HAT, including 78 with a positive parasitology, were tested with the CATT-FP and duplicate filter paper samples were sent to a reference laboratory to assess reproducibility. The CATT-FP was positive in 90 of 99 patients with HAT (sensitivity: 91%). It was less sensitive than the CATT-P (mean dilution difference: -2.5). There was no significant loss of sensitivity after storage for up to 14 days both at ambient and cool temperature. Reproducibility of the CATT-FP was found to be excellent (kappa: 0.84). The CATT-FP can therefore be recommended as a screening test for HAT in areas where the use of CATT-P is not possible. Further studies on larger population samples in different endemic foci are still needed before the CATT-FP can be recommended for universal use.
    • Treatment of human African trypanosomiasis--present situation and needs for research and development.

      Legros, D; Ollivier, G; Gastellu-Etchegorry, M; Paquet, C; Burri, C; Jannin, J; Büscher, P; Epicentre, Paris, France. dlegros@epicentre.msf.org (Elsevier, 2002-07)
      Human African trypanosomiasis re-emerged in the 1980s. However, little progress has been made in the treatment of this disease over the past decades. The first-line treatment for second-stage cases is melarsoprol, a toxic drug in use since 1949. High therapeutic failure rates have been reported recently in several foci. The alternative, eflornithine, is better tolerated but difficult to administer. A third drug, nifurtimox, is a cheap, orally administered drug not yet fully validated for use in human African trypanosomiasis. No new drugs for second-stage cases are expected in the near future. Because of resistance to and limited number of current treatments, there may soon be no effective drugs available to treat trypanosomiasis patients, especially second-stage cases. Additional research and development efforts must be made for the development of new compounds, including: testing combinations of current trypanocidal drugs, completing the clinical development of nifurtimox and registering it for trypanosomiasis, completing the clinical development of an oral form of eflornithine, pursuing the development of DB 289 and its derivatives, and advancing the pre-clinical development of megazol, eventually engaging firmly in its clinical development. Partners from the public and private sector are already engaged in joint initiatives to maintain the production of current drugs. This network should go further and be responsible for assigning selected teams to urgently needed research projects with funds provided by industry and governments. At the same time, on a long term basis, ambitious research programmes for new compounds must be supported to ensure the sustainable development of new drugs.
    • Availability and affordability of treatment for Human African Trypanosomiasis.

      Etchegorry, M; Helenport, J; Pecoul, B; Jannin, J; Legros, D; Médecins Sans Frontières, 8 Rue Saint Sabin, Paris. (Wiley-Blackwell, 2001-11)
      Human African Trypanosomiasis (HAT) is a re-emerging disease whose usual treatments are becoming less efficient because of the increasing parasite resistance. Availability of HAT drugs is poor and their production in danger because of technical, ecological and economic constraints. In view of this dramatic situation, a network involving experts from NGOs, WHO and pharmaceutical producers was commissioned with updating estimates of need for each HAT drug for the coming years; negotiations with potential producers of new drugs such as eflornithine; securing sustainable manufacturing of existing drugs; clinical research into new combinations of these drugs for first and second-line treatments; centralizing drug purchases and their distribution through a unique non-profit entity; and addressing regulatory and legal issues concerning new drugs.
    • Human african trypanosomiasis: A history of its therapies and their failures.

      Ollivier, G; Legros, D; Epicentre, Paris, France. (Wiley-Blackwell, 2001-11)
      This paper gives an overview of the treatment of Human African Trypanosomiasis from the early 20th century until today.