To see all articles in this section, click on "browse by Title".

Recent Submissions

  • Chagas disease knocks on our door: a cross-sectional study among Latin American immigrants in Milan, Italy.

    Antinori, S; Galimberti, L; Grande, R; Bianco, R; Oreni, L; Traversi, L; Ricaboni, D; Bestetti, G; Lai, A; Mileto, D; et al. (Elsevier, 2018-12-01)
    OBJECTIVES: We aimed to assess the prevalence and risk factors for Chagas disease (CD) in Latin American immigrants and to evaluate the accuracy of diagnostic tests. Moreover, we offered to all positive subjects a complete free-of-charge clinical/instrumental evaluation as well as benznidazole treatment in order to stage the disease and verify drug tolerability. METHODS: A cross-sectional survey of CD among Latin Americans living in Milan and its metropolitan area was conducted between July 2013 and July 2014. Blood samples were tested for serologic evidence of CD together with a questionnaire covering demographic and clinical-epidemiological information. RESULTS: Forty-eight (9.6%) of the 501 tested subjects were conclusively diagnosed as having CD. The highest prevalence of CD was among those from Bolivia (43/169, 25.4%) and El Salvador (4/68, 5.9%). Older age (adjusted odds ratio (aOR)] 1.05, p =0.004), a Bolivian origin (aOR 8.80; p =0.003), being born in the department of Santa Cruz (aOR 3.72, p =0.047), having lived in mud houses (aOR 2.68; p =0.019), and having an affected relative (aOR 12.77, p =0.001) were independently associated with CD. The ARCHITECT Chagas test showed the highest sensitivity (100%) and specificity (99.8%). Twenty-nine of the subjects with CD (60.4%) underwent disease staging, 10 of whom (35.7%) showed cardiac and/or digestive involvement. Benznidazole treatment was associated with high frequency of adverse reactions (19/27, 70.4%) and permanent discontinuation (8/27, 29.6%). CONCLUSIONS: CD is highly prevalent among Bolivians and Salvadorans living in Milan. Regions with a large Latin American immigrant population should implement programmes of active detection and treatment.
  • 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.
  • Updated estimate of the duration of the meningo-encephalitic stage in gambiense human African trypanosomiasis

    Checchi, F; Funk, S; Chandramohan, D; Haydon, D T; Chappuis, F (BMC, 2015-07-04)
    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.
  • 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.
  • 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.
  • Nifurtimox-Eflornithine Combination Therapy for Second-stage Gambiense Human African Trypanosomiasis: Médecins Sans Frontières experience in the Democratic Republic of the Congo

    Alirol, E; Schrumpf, D; Amici Heradi, J; Riedel, A; de Patoul, C; Quere, M; Chappuis, F; Division of International and Humanitarian Medicine, University Hospitals of Geneva, Switzerland. (Oxford University Press, 2012-11-09)
    Existing diagnostic and treatment tools for human African trypanosomiasis (HAT) are limited. The recent development of nifurtimox-eflornithine combination therapy (NECT) has brought new hopes for patients in the second stage. While NECT has been rolled out in most endemic countries, safety data are scarce and derive only from clinical trials. The World Health Organization (WHO) coordinates a pharmacovigilance program to collect additional data on NECT safety and efficacy. We report here the results of 18 months of experience of NECT use in treatment centers run by Médecins Sans Frontières in the Democratic Republic of the Congo (DRC).
  • 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. (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.
  • 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. (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.
  • Challenges of controlling sleeping sickness in areas of violent conflict: experience in the Democratic Republic of Congo.

    Tong, J; Valverde, O; Mahoudeau, C; Yun, O; Chappuis, F; Médecins Sans Frontières, Rue de Lausanne 78, 1211 Geneva, Switzerland. (BioMed Central, 2011-05-26)
    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.
  • Sleeping sickness

    Malvy, D; Chappuis, F; Travel Clinics and Division of Tropical Medicine and Imported Diseases, Department of Internal Medicine and Tropical Diseases, University Hospital Centre, Bordeaux, France; Universite de Bordeaux, Faculty of Medicine, INSERM U897 and Centre Rene-Labusquiere (Tropical Medicine Branch), Bordeaux, France; Division of International and Humanitarian Medicine, Geneva University Hospital, Switzerland; Medecins Sans Frontieres, Operational Centre, Geneva, Switzerland (Wiley-Blackwell, 2011-04-04)
    Human African trypanosomiasis (HAT), or sleeping sickness, is a vector-borne disease that flourishes in impoverished, rural parts of sub-Saharan Africa. It is caused by infection with the protozoan parasite Trypanosoma brucei and is transmitted by tsetse flies of the genus Glossina. The majority of cases are caused by T. b. gambiense, which gives rise to the chronic, anthroponotic endemic disease in Western and Central Africa. Infection with T. b. rhodesiense leads to the acute, zoonotic form of Eastern and Southern Africa. The parasites live and multiply extracellularly in the blood and tissue fluids of their human host. They have elaborated a variety of strategies for invading hosts, to escape the immune system and to take advantage of host growth factors. HAT is a challenging and deadly disease owing to its complex epidemiology and clinical presentation and, if left untreated, can result in high death rates. As one of the most neglected tropical diseases, HAT is characterized by the limited availability of safe and cost-effective control tools. No vaccine against HAT is available, and the toxicity of existing old and cumbersome drugs precludes the adoption of control strategies based on preventive chemotherapy. As a result, the keystones of interventions against sleeping sickness are active and passive case-finding for early detection of cases followed by treatment, vector control and animal reservoir management. New methods to diagnose and treat patients and to control transmission by the tsetse fly are needed to achieve the goal of global elimination of the disease.
  • 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.
  • 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)
  • Human African trypanosomiasis in areas without surveillance.

    Chappuis, F; Lima, M A; Flevaud, L; Ritmeijer, K; Médecins Sans Frontières, Geneva, Switzerland; Geneva University Hospitals, Geneva, Switzerland; Médecins sans Frontières, Barcelona, Spain; Médecins sans Frontières, Amsterdam, the Netherlands (2010-02-01)
  • Human African trypanosomiasis

    Brun, R; Blum, J; Chappuis, F; Burri, C; Swiss Tropical Institute, Basel, Switzerland; Geneva University Hospitals, University of Geneva, Switzerland; Médecins Sans Frontières, Geneva, Switzerland (2009-10-14)
    Human African trypanosomiasis (sleeping sickness) occurs in sub-Saharan Africa. It is caused by the protozoan parasite Trypanosoma brucei, transmitted by tsetse flies. Almost all cases are due to Trypanosoma brucei gambiense, which is indigenous to west and central Africa. Prevalence is strongly dependent on control measures, which are often neglected during periods of political instability, thus leading to resurgence. With fewer than 12 000 cases of this disabling and fatal disease reported per year, trypanosomiasis belongs to the most neglected tropical diseases. The clinical presentation is complex, and diagnosis and treatment difficult. The available drugs are old, complicated to administer, and can cause severe adverse reactions. New diagnostic methods and safe and effective drugs are urgently needed. Vector control, to reduce the number of flies in existing foci, needs to be organised on a pan-African basis. WHO has stated that if national control programmes, international organisations, research institutes, and philanthropic partners engage in concerted action, elimination of this disease might even be possible.
  • 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.
  • Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial

    Priotto, G; Kasparian, S; Mutombo, W; Ngouama, D; Ghorashian, S; Arnold, U; Ghabri, S; Baudin, E; Buard, V; Kazadi-Kyanza, S; et al. (Elsevier, 2009-07-04)
    Background Human African trypanosomiasis (HAT; sleeping sickness) caused by Trypanosoma brucei gambiense is a fatal disease. Current treatment options for patients with second-stage disease are toxic, ineffective, or impractical. We assessed the efficacy and safety of nifurtimox-eflornithine combination therapy (NECT) for second-stage disease compared with the standard eflornithine regimen. Methods A multicentre, randomised, open-label, active control, phase III, non-inferiority trial was done at four HAT treatment centres in the Republic of the Congo and the Democratic Republic of the Congo. Patients aged 15 years or older with confirmed second-stage T b gambiense infection were randomly assigned by computer-generated randomisation sequence to receive intravenous eflornithine (400 mg/kg per day, every 6 h; n=144) for 14 days or intravenous eflornithine (400 mg/kg per day, every 12 h) for 7 days with oral nifurtimox (15 mg/kg per day, every 8 h) for 10 days (NECT; n=143). The primary endpoint was cure (defined as absence of trypanosomes in body fluids and a leucocyte count ≤20 cells per μL) 18 months after treatment. Efficacy analyses were done in the intention-to-treat (ITT), modified ITT, and per-protocol (PP) populations. The non-inferiority margin for the difference in cure rates was defined as 10%. This study is registered with, number NCT00146627. Findings One patient from the eflornithine group absconded after receiving the first dose, without any type of assessment done, and was excluded from all analyses. In the ITT population, 131 (91·6%) of 143 patients assigned to eflornithine and 138 (96·5%) of 143 patients assigned to NECT were cured at 18 months (difference −4·9%, one-sided 95% CI −0·3; p<0·0001). In the PP population, 122 (91·7%) of 133 patients in the eflornithine group and 129 (97·7%) of 132 in the NECT group were cured at 18 months (difference −6·0%, one-sided 95% CI −1·5; p<0·0001). Drug-related adverse events were frequent in both groups; 41 (28·7%) patients in the eflornithine group and 20 (14·0%) in the NECT group had major (grade 3 or 4) reactions, which resulted in temporary treatment interruption in nine and one patients, respectively. The most common major adverse events were fever (n=18), seizures (n=6), and infections (n=5) in the eflornithine group, and fever (n=7), seizures (n=6), and confusion (n=2) in the NECT group. There were four deaths, which were regarded as related to study drug (eflornithine, n=3; NECT, n=1). Interpretation The efficacy of NECT is non-inferior to that of eflornithine monotherapy. Since this combination treatment also presents safety advantages, is easier to administer (ie, infusion every 12 h for 7 days vs every 6 h for 14 days), and potentially protective against the emergence of resistant parasites, it is suitable for first-line use in HAT control programmes. Funding Médecins Sans Frontières (Dutch section), Médecins Sans Frontières International, and the Drugs for Neglected Diseases Initiative.
  • Médecins Sans frontières (MSF) and sleeping sickness control. From bush to international health space

    d'Alessandro, E; CNRS UMR 6578 et Fondation MSF. (2009-02)
    In this article, we propose a history of Médecins Sans Frontières's control activities to fight human african trypanosomiasis. Through this history are enlightening medical innovations in the scope of diagnostic and treatment of the disease. MSF investing will focus successively on (1) epidemiological and clinical diagnosis, (2) existing drugs evaluation and (3) development of new therapeutic protocols. After a period of isolation, MSF will have to cooperate with others international health organizations. Specific questions on medical practice and research in the south countries will represent the major issues regarding medical innovation.
  • Effectiveness of melarsoprol and eflornithine as first-line regimens for gambiense sleeping sickness in nine Médecins Sans Frontières programmes.

    Balasegaram, M; Young, H; Chappuis, F; Priotto, G; Raguenaud, M E; Checchi, F; Médecins Sans Frontières-United Kingdom, 67-74 Saffron Hill, London EC1N 8QX, UK. (2008-10-21)
    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.
  • Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study

    Priotto, G; Pinoges, L; Badi Fursa, I; Burke, B; Nicolay, N; Grillet, G; Hewison, C; Balasegaram, M; Epicentre, Paris, France; Médecins Sans Frontières, Paris, France (2008-03-05)
    Objective: To assess the safety and effectiveness of eflornithine as first line treatment for human African trypanosomiasis. Design: Cohort study. Setting: Control programme in Ibba, southern Sudan. Participants: 1055 adults and children newly diagnosed with second stage disease in a 16 month period. Main outcome measures: Deaths, severe drug reactions, and cure at 24 months. Results: 1055 patients received eflornithine for 14 days (400 mg/kg/day in adults and 600 mg/kg/day in a subgroup of 96 children). Overall, 2824 drug reactions (2.7 per patient) occurred during hospital stay, 1219 (43.2%) after the first week. Severe reactions affected 138 (13.1%) patients (mainly seizures, fever, diarrhoea, and bacterial infections), leading to 15 deaths. Risk factors for severe reactions included cerebrospinal fluid leucocyte counts ≥100x109/l (adults: odds ratio 2.6, 95% confidence interval 1.5 to 4.6), seizures (adults: 5.9, 2.0 to 13.3), and stupor (children: 9.3, 2.5 to 34.2). Children receiving higher doses did not experience increased toxicity. Follow-up data were obtained for 924 (87.6%) patients at any follow-up but for only 533 (50.5%) at 24 months. Of 924 cases followed, 16 (1.7%) died during treatment, 70 (7.6%) relapsed, 15 (1.6%) died of disease, 403 (43.6%) were confirmed cured, and 420 (45.5%) were probably cured. The probability of event free survival at 24 months was 0.88 (0.86 to 0.91). Most (65.8%, 52/79) relapses and disease related deaths occurred after 12 months. Risk factors for relapse included being male (incidence rate ratio 2.42, 1.47 to 3.97) and cerebrospinal fluid leucocytosis: 20-99x109/l (2.35, 1.36 to 4.06); ≥100x109/l (1.87, 1.07 to 3.27). Higher doses did not yield better effectiveness among children (0.87 v 0.85, P=0.981). Conclusions: Eflornithine shows acceptable safety and effectiveness as first line treatment for human African trypanosomiasis. Relapses did occur more than 12 months after treatment. Higher doses in children were well tolerated but showed no advantage in effectiveness.

View more