• Raising Standards in Emergency Relief: How Useful are Sphere Minimum Standards for Humanitarian Assistance?

      Griekspoor, A; Collins, S; Médecins Sans Frontières, Amsterdam, Netherlands. grickspoora@who.ch (Published by: BMJ Publishing Group Ltd, 2001-09-29)
    • A Randomised Phase II Trial to Evaluate the Toxicity of High-Dose Rifampicin to Treat Pulmonary Tuberculosis

      Jindani, A; Borgulya, G; de Patiño, I W; Gonzales, T; de Fernandes, RA; Shrestha, B; Atwine, D; Bonnet, M; Burgos, M; Dubash, F; et al. (International Union Against Tuberculosis and Lung Disease, 2016-06-01)
      Randomised Phase IIB clinical trial.
    • A randomized comparison of branded sodium stibogluconate and generic sodium stibogluconate for the treatment of visceral leishmaniasis under field conditions in Sudan.

      Veeken, H; Ritmeijer, K; Seaman, J; Davidson, R N; Médecins Sans Frontières Holland, Amsterdam, The Netherlands. hans_veeken@amsterdam.msf.org (Wiley-Blackwell, 2000-05)
      OBJECTIVE: To compare the outcome of treatment of Sudanese kala-azar patients treated under field conditions with either branded sodium stibogluconate (SSG) (Pentostam GlaxoWellcome) or generic SSG (Albert David Ltd, Calcutta, supplied by International Dispensary Association, Amsterdam). METHOD: Randomised comparison. 271 patients were treated with Pentostam and 245 with generic SSG. RESULTS: No statistically significant differences in cure rate or mortality were detected between Pentostam and generic SSG. No differences in side-effects between the two drugs were noted. The initial cure rate at the time of discharge was 93.7 and 97.6%, respectively; the death rate during treatment 5.9 and 2.4%. Six months follow up was achieved in 88.5% of the discharged patients. Two patients had died in the Pentostam group and two had died in the generic SSG group, giving a final death rate of 7.5 and 3.7%. The number of relapses in the Pentostam and generic SSG groups were 3 and 1, respectively. The final cure rates, calculated at 6 months after discharge, were 91.3% and 95.9%. CONCLUSION: No difference was observed in the performance of generic SSG compared to Pentostam for the treatment of visceral leishmaniasis in Sudan. Generic SSG can be routinely and safely used for the treatment of kala-azar. Generic SSG costs only 1/14 of the price of Pentostam. The use of generic SSG may make treatment of kala-azar affordable for national governments in Africa.
    • A randomized open study to assess the efficacy and tolerability of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Cambodia.

      Janssens, B; Van Herp, M; Goubert, L; Chan, S; Uong, S; Nong, S; Socheat, D; Brockman, A; Ashley, E A; Van Damme, W; et al. (Wiley-Blackwell, 2007-02)
      OBJECTIVES: To compare the efficacy and tolerability of dihydroartemisinin-piperaquine (DHA-PQP) with that of a 3-day regimen of mefloquine and artesunate (MAS3) for the treatment of uncomplicated falciparum malaria in Cambodia. METHOD: Randomized open-label non-inferiority study over 64 days. RESULTS: Four hundred and sixty-four patients were included in the study. The polymerase chain reaction genotyping-adjusted cure rates on day 63 were 97.5% (95% confidence interval, CI, 93.8-99.3) for DHA-PQP and 97.5% (95% CI, 93.8-99.3) for MAS3, P = 1. There were no serious adverse events, but significantly more episodes of vomiting (P = 0.03), dizziness (P = 0.002), palpitations (P = 0.04), and sleep disorders (P = 0.03) reported in the MAS3 treatment group, consistent with the side-effect profile of mefloquine. CONCLUSIONS: DHA-PQP was as efficacious as MAS3, but much better tolerated, making it more appropriate for use in a routine programme setting. This highly efficacious, safe and more affordable fixed-dose combination could become the treatment of choice for Plasmodium falciparum malaria in Cambodia.
    • A randomized trial comparing the efficacy of four treatment regimens for uncomplicated falciparum malaria in Assam state, India.

      Campbell, P; Baruah, S; Narain, K; Rogers, C C; Medecins sans Frontieres-Holland, India Section, R.G. Baruah Road, Guwahati, Assam 781024, India. patricia10334@yahoo.com (Elsevier, 2006-02)
      A four-arm drug sensitivity study compared chloroquine, sulfadoxine-pyrimethamine (SP), mefloquine and mefloquine-artesunate in Sonitpur and Karbi Anglong districts in Assam state, India. Two criteria were used to ascertain outcome: success of clinical treatment and parasitologic cure. In Sonitpur, at 14 days, there were 36/56 early and late treatment failures plus late parasitologic failures to chloroquine and 16/56 for SP. In Karbi Anglong, combined treatment failure at 14 days was 16/56 to chloroquine and 8/60 to SP. Mefloquine and mefloquine-artesunate demonstrated 93.9% and 93.6% sustained responses respectively at 42 days. High failure rates to both chloroquine and SP preclude the use of these drugs as first-line treatment for uncomplicated falciparum malaria in this region. A mefloquine-artesunate combination presents an effective alternative utilizing the currently recommended higher dose of mefloquine.
    • A Randomized Trial of AmBisome Monotherapy and AmBisome and Miltefosine Combination to Treat Visceral leishmaniasis in HIV Co-infected Patients in Ethiopia

      Diro, E; Blesson, S; Edwards, T; Ritmeijer, K; Fikre, H; Admassu, H; Kibret, A; Ellis, SJ; Bardonneau, C; Zijlstra, EE; et al. (Public Library of Science, 2019-01-17)
      Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.
    • Randomized trials to optimize treatment of multidrug-resistant tuberculosis

      Mitnick, C D; Castro, K G; Harrington, M; Sacks, L V; Burman, W; Harvard Medical School, Boston, MA, USA; Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA; Treatment Action Group, New York, NY, USA; Food and Drug Administration, Rockville, MD, USA; Denver Public Health and University of Colorado Health Sciences Center, Denver, CO, USA (2007-11-06)
    • A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

      Mulangu, S; Grais, R; Dodd, L; Follmann, D; Proschan, M; Davey, R; Mukadi, D; Lusakibanza, M (2019-12-12)
      BACKGROUND Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. METHODS We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase–polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. RESULTS A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. CONCLUSIONS Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.)
    • Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda

      Grais, R; Warimwe, G; Kimathi, D; Juan, A; Bejon, P; epicentre (F1000 Research Ltd, 2019-11-20)
      Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa. Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days – up to 2 years – post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose. Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops.
    • Ranking malaria risk factors to guide malaria control efforts in African highlands

      Protopopoff, Natacha; Van Bortel, Wim; Speybroeck, Niko; Van Geertruyden, Jean-Pierre; Baza, Dismas; D'Alessandro, Umberto; Coosemans, Marc; Department of Parasitology, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; Medecins Sans Frontieres Brussels, Belgium; Department of Animal Health, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium; School of Public Health, Universite Catholique de Louvain, Brussels, Belgium; Programme de Lutte contre les Maladies Transmissibles et Carentielles, Ministry of Health, Bujumbura, Burundi; Department of Biomedical Sciences, Faculty of Pharmaceutical, Veterinary and Biomedical Sciences, University of Antwerp, Antwerp, Belgium (2009-11-25)
      INTRODUCTION: Malaria is re-emerging in most of the African highlands exposing the non immune population to deadly epidemics. A better understanding of the factors impacting transmission in the highlands is crucial to improve well targeted malaria control strategies. METHODS AND FINDINGS: A conceptual model of potential malaria risk factors in the highlands was built based on the available literature. Furthermore, the relative importance of these factors on malaria can be estimated through "classification and regression trees", an unexploited statistical method in the malaria field. This CART method was used to analyse the malaria risk factors in the Burundi highlands. The results showed that Anopheles density was the best predictor for high malaria prevalence. Then lower rainfall, no vector control, higher minimum temperature and houses near breeding sites were associated by order of importance to higher Anopheles density. CONCLUSIONS: In Burundi highlands monitoring Anopheles densities when rainfall is low may be able to predict epidemics. The conceptual model combined with the CART analysis is a decision support tool that could provide an important contribution toward the prevention and control of malaria by identifying major risk factors.
    • Rapid assessment of mortality and malnutrition in Afghanistan.

      Piola, P; Tachon, J L; Brown, V; Ligozat, L; Veyrier, E; Nierle, T; Ford, N; Legros, D (2002-09-11)
    • Rapid culture-based methods for drug-resistance detection in Mycobacterium tuberculosis.

      Palomino, J C; Martin, A; Von Groll, A; Portaels, F; Mycobacteriology Unit, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium. (Elsevier, 2008-10)
      Tuberculosis still represents a major public health problem, especially in low-resource countries where the burden of the disease is more important. Multidrug-resistant and extensively drug drug-resistant tuberculosis constitute serious problems for the efficient control of the disease stressing the need to investigate resistance to first- and second-line drugs. Conventional methods for detecting drug-resistance in Mycobacterium tuberculosis are slow and cumbersome. The most commonly used proportion method on Löwenstein-Jensen medium or Middlebrook agar requires a minimum of 3-4 weeks to produce results. Several new approaches have been proposed in the last years for the rapid and timely detection of drug-resistance in tuberculosis. This review will address phenotypic culture-based methods for rapid drug susceptibility testing in M. tuberculosis.
    • Rapid detection of Mycobacterium tuberculosis resistance to second-line drugs by use of the manual mycobacterium growth indicator tube system.

      Martin, A; von Groll, A; Fissette, K; Palomino, J C; Varaine, F; Portaels, F; Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium. amartin@itg.be (2008-12)
      The objective of this study was to evaluate the manual mycobacterium growth indicator tube (MGIT) system for the testing of Mycobacterium tuberculosis susceptibility to second-line drugs compared to the proportion method. One hundred eighty-eight M. tuberculosis isolates were tested for susceptibility to ofloxacin, kanamycin, ethionamide, and capreomycin by the manual MGIT, and results were compared to those obtained with the proportion method on 7H11 agar, considered a reference method. Results for ofloxacin and capreomycin were excellent, with 100% accuracy, and a result of 99.4% accuracy was achieved for kanamycin. For ethionamide, accuracy was lower, with a result of 86.7% compared to that of the proportion method. We proposed the following critical concentrations for the drugs: for ofloxacin, 2.0 microg/ml; for kanamycin, 2.5 microg/ml; for ethionamide, 5 microg/ml; and for capreomycin, 2.5 microg/ml. The time required to obtain results was an average of 8 days by the manual MGIT and 3 weeks by the reference method. Our results show that the manual MGIT is an accurate method for the rapid susceptibility testing of M. tuberculosis to second-line drugs. There is no need for a machine when using the manual MGIT, and results can be read with a simple UV lamp or with a semiquantitative reader, which considerably reduces the cost of the method.
    • Rapid Diagnostic Tests for Non-Malarial Febrile Illness in the Tropics

      Chappuis, F; Alirol, E; d'Acremont, V; Bottieau, E; Yansouni, C P; Division of International and Humanitarian Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland; Médecins Sans Frontières, Operational Centre Geneva, Geneva, Switzerland. (2013-02-15)
      The recent roll-out of rapid diagnostic tests (RDTs) for malaria has highlighted the decreasing proportion of malaria-attributable illness in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low resource settings. This review summarizes the current state of RDT development for several key infections, including dengue fever, enteric fever, leptospirosis, brucellosis, visceral leishmaniasis and human African trypanosomiasis, and highlights many remaining gaps. Most RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent. The sensitivity and specificity of host-antibody detection tests are both inherently limited. Moreover, prolonged antibody responses to many infections preclude the use of most serological RDTs for monitoring response to treatment and/or for diagnosing relapse. Considering these limitations, there is a pressing need for sensitive pathogen-detection-based RDTs, as have been successfully developed for malaria and dengue. Ultimately, integration of RDTs into a validated syndromic approach to tropical fevers is urgently needed. Related research priorities are to define the evolving epidemiology of fever in the tropics, and to determine how combinations of RDTs could be best used to improve the management of severe and treatable infections requiring specific therapy.
    • Rapid malaria diagnostic tests vs. clinical management of malaria in rural Burkina Faso: safety and effect on clinical decisions. A randomized trial

      Bisoffi, Zeno; Sirima, Bienvenu Sodiomon; Angheben, Andrea; Lodesani, Claudia; Gobbi, Federico; Tinto, Halidou; Van den Ende, Jef; Centre for Tropical Diseases, Sacro Cuore Hospital, Negrar (Verona), Italy; Centre National de Recherche et de Formation sur le Paludisme, Ministry of Health, Ouagadougou, Burkina Faso; Medecins sans Frontieres, Democratic Republic of Congo; Centre Muraz, Bobo Dioulasso, Burkina Faso; Projet AnKaHeresso, Bobo Dioulasso, Burkina Faso; Department of Clinical Sciences, Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium (2009-02-15)
      OBJECTIVES: To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria (RDT) is at least equivalent to that of controls (treated presumptively without test) and to determine the impact of the introduction of a malaria RDT on clinical decisions. METHODS: Randomized, multi-centre, open clinical trial in two arms in 2006 at the end of the dry and of the rainy season in 10 peripheral health centres in Burkina Faso: one arm with use of RDT before treatment decision, one arm managed clinically. Primary endpoint: persistence of fever at day 4. Secondary endpoints: frequency of malaria treatment and of antibiotic treatment. RESULTS: A total of 852 febrile patients were recruited in the dry season and 1317 febrile patients in the rainy season, and randomized either to be submitted to RDT (P_RTD) or to be managed presumptively (P_CLIN). In both seasons, no significant difference was found between the two randomized groups in the frequency of antimalarial treatment, nor of antibiotic prescription. In the dry season, 80.8% and 79.8% of patients with a negative RDT were nevertheless diagnosed and treated for malaria, and so were 85.0% and 82.6% negative patients in the rainy season. In the rainy season only, both diagnosis and treatment of other conditions were significantly less frequent in RDT positive vs. negative patients (48.3% vs. 61.4% and 46.2% vs. 59.9%, P = 0.00 and 0.00, respectively). CONCLUSION: Our study was inconclusive on RDT safety (clinical outcome in the two randomized groups), because of an exceedingly and unexpectedly low compliance with the negative test result. Further research is needed on best strategies to promote adherence and on the safety of a test based strategy compared with the current, presumptive treatment strategy.
    • A rapid screening tool for Psychological Distress in children 3-6 years old: results of a Validation Study

      Marquer, C; Barry, C; Mouchenik, Y; Hustache, S; Djibo, D; Manzo, M; Falissard, B; Révah-Lévy, A; Grais, R; Moro, M-R; et al. (2012-08-16)
      The mental health needs of young children in humanitarian contexts often remain unaddressed. The lack of a validated, rapid and simple tool for screening combined with few mental health professionals able to accurately diagnose and provide appropriate care mean that young children remain without care. Here, we present the results of the principle cross-cultural validation of the "Psychological Screening for Young Children aged 3 to 6" (PSYCAa3-6). The PSYCa 3-6 is a simple scale for children 3 to 6 years old administered by non-specialists, to screen young children in crises and thereby refer them to care if needed.
    • Rates and Causes of Death in Chiradzulu District, Malawi, 2008: A Key Informant Study

      Checchi, Francesco; Nyasulu, Peter; Chandramohan, Daniel; Roberts, Bayard; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK; Médecins Sans Frontières, Blantyre, Malawi; Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, UK (2010-12-03)
      In September 2008, we measured all-cause mortality in Chiradzulu District, Malawi (population 291 000) over a 60-day retrospective period, using capture-recapture analysis of three lists of deaths provided by (i) key community informants, (ii) graveyard officials and (iii) health system sources. Estimated crude and under-5-year mortality rates were 18.6 (95% CI 13.9-24.5) and 30.6 (95% CI 17.5-59.9) deaths per 1000 person-years. We also classified causes of death through verbal autopsy interviews on 50 deaths over the previous 40 days. Half of deaths were attributable to infection, and half of deaths among children aged under 5 were attributable to neonatal causes. HIV/AIDS was the leading cause of death (16.6%), with a cause-attributable mortality rate of 1.8 (0.4-3.6) deaths per 1000 person-years.
    • Rational use of moxifloxacin for tuberculosis treatment

      Cox, H; Ford, N; Keshavjee, S; McDermid, C; von Schoen-Angerer, T; Mitnick, C; Goemaere, E; Burnet Institute, Melbourne, Australia; Médecins Sans Frontières, Johannesburg, South Africa; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; Harvard Medical School, Boston, USA; Partners in Health, Boston, USA; Médecins Sans Frontières Campaign for Access to Essential Medicines, Geneva, Switzerland (2011-04-01)
    • Rationing antiretroviral therapy in Africa--treating too few, too late.

      Ford, N; Mills, E; Calmy, A; Medical unit, Médecins sans Frontières, and School of Public Health and Family Medicine, University of Cape Town, South Africa. (2009-04-30)
    • Re-Inventing Adherence: Toward a Patient-Centered Model of Care for Drug-Resistant Tuberculosis and HIV

      O'Donnell, M R; Daftary, A; Frick, M; Hirsch-Moverman, Y; Amico, K R; Senthilingam, M; Wolf, A; Metcalfe, J Z; Isaakidis, P; Davis, J L; et al. (International Union Against TB and Lung Disease, 2016-04-01)
      Despite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care.