• Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis.

      Checchi, F; Chappuis, F; Karunakara, U; Priotto, G; Chandramohan, D; London School of Hygiene and Tropical Medicine, United Kingdom. Francesco.checchi@lshtm.ac.uk (2011-07)
      Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda.
    • Early prediction of treatment efficacy in Second-Stage Gambiense Human African Trypanosomiasis

      Priotto, G; Chappuis, F; Bastard, M; Flevaud, L; Etard, J-F; Epicentre, Paris, France. gpriotto@neuf.fr (2012-06-05)
      Human African trypanosomiasis is fatal without treatment. The long post-treatment follow-up (24 months) required to assess cure complicates patient management and is a major obstacle in the development of new therapies. We analyzed individual patient data from 12 programs conducted by Médecins Sans Frontières in Uganda, Sudan, Angola, Central African Republic, Republic of Congo and Democratic Republic of Congo searching for early efficacy indicators.
    • Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies

      Burri, C; Yeramian, P D; Allen, J L; Merolle, A; Serge, K K; Mpanya, A; Lutumba, P; Mesu, V K; Bilenge, C M; Lubaki, J P; et al. (Public Library of Science, 2016-02-16)
      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.
    • Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières

      Yun, O; Lima, M A; Ellman, T; Chambi, W; Castillo, S; Flevaud, L; Roddy, P; Parreño, F; Albajar Viñas, P; Palma, P P; et al. (Public Library of Science, 2009-07-07)
      BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed.
    • Human african trypanosomiasis in the democratic republic of the congo: a looming emergency?

      Hasker, E; Lutumba, P; Chappuis, F; Kande, V; Potet, J; De Weggheleire, A; Kambo, C; Depoortere, E; Pécoul, B; Boelaert, M; et al. (2012-12)
    • In-hospital safety in field conditions of Nifurtimox Eflornithine Combination Therapy (NECT) for T. B. Gambiense Sleeping Sickness

      Schmid, C; Kuemmerle, A; Blum, J; Ghabri, S; Kande, V; Mutombo, W; Ilunga, M; Lumpungu, I; Mutanda, S; Nganzobo, P; et al. (2012-11-29)
      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.
    • NECT is next: implementing the new drug combination therapy for Trypanosoma brucei gambiense sleeping sickness.

      Yun, O; Priotto, G; Tong, J; Flevaud, L; Chappuis, F; Médecins Sans Frontières/Doctors Without Borders, New York, New York, USA; Epicentre, Paris, France; Médecins Sans Frontières, Geneva, Switzerland; Médecins Sans Frontières, Barcelona, Spain; Geneva University Hospitals, Geneva, Switzerland (2010-05-25)
    • 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.
    • Profile of Trypanosoma cruzi Infection in a Tropical Medicine Reference Center, Northern Italy

      Gobbi, F; Angheben, A; Anselmi, M; Postiglione, C; Repetto, E; Buonfrate, D; Marocco, S; Tais, S; Chiampan, A; Mainardi, P; et al. (Public Library of Science, 2014-12-11)
      Chagas disease (CD) is endemic in Central and South America, Mexico and even in some areas of the United States. However, cases have been increasingly recorded also in non-endemic countries. The estimated number of infected people in Europe is in a wide range of 14000 to 181000 subjects, mostly resident in Spain, Italy and the United Kingdom.
    • The Unknown Risk of Vertical Transmission in Sleeping Sickness--a Literature Review

      Lindner, A K; Priotto, G; London School of Hygiene & Tropical Medicine, United Kingdom; Epicentre, France (2010-12-21)
      Children with human African trypanosomiasis (HAT) present with a range of generally non-specific symptoms. Late diagnosis is frequent with often tragic outcomes. Trypanosomes can infect the foetus by crossing the placenta. Unequivocal cases of congenital infection that have been reported include newborn babies of infected mothers who were diagnosed with HAT in the first 5 days of life and children of infected mothers who had never entered an endemic country themselves.