• Biological diagnosis of meningococcal meningitis in the African meningitis belt: current epidemic strategy and new perspectives.

      Chanteau, S; Rose, A; Djibo, S; Nato, F; Boisier, P; CERMES, Réseau International Institut Pasteur, PO Box 10887, Niamey, Niger. schanteau@cermes.org (Elsevier, 2007-09-03)
      Laboratory diagnosis is an essential component in surveillance of meningococcal epidemics, as it can inform decision-makers of the Neisseria meningitidis serogroup(s) involved and the most appropriate vaccine to be selected for mass vaccination. However, countries most affected face real limitations in laboratory diagnostics, due to lack of resources. We describe current diagnostic tools and examine their cost-effectiveness for use in an epidemic context. The conclusion is that current WHO recommendations to use only the latex agglutination assay (Pastorex) at epidemic onset is cost-effective, but recently developed rapid diagnostic tests for the major epidemic-causing meningococcal serogroups may prove a breakthrough for the future.
    • Developments in the treatment of visceral leishmaniasis

      den Boer, Margriet Leontine; Alvar, Jorge; Davidson, Robert N; Ritmeijer, Koert; Balasegaram, Manica; Medecins Sans Frontieres, Amsterdam, The Netherlands (2009-09-01)
      BACKGROUND: Visceral leishmaniasis (VL) is one of the most neglected parasitic diseases causing large scale mortality and morbidity among the poorest of the poor in the Indian subcontinent and Africa. OBJECTIVE: This review aims to describe the potential and the (lack of) current impact of newly developed treatments on the control of VL. It describes how the problem of an empty research pipeline is addressed, and discusses the emerging threat of incurable HIV/VL coinfection. METHODS: The literature was searched for drugs used in VL. CONCLUSION: Research and development of VL drugs has received a financial boost but no new drugs are expected in the next 5 years. Only three new and highly effective treatments have been licensed in the past 10 years. These remain, however, largely inaccessible as VL control programs in the developing world are lacking. This is deserving of immediate and urgent attention, especially in the context of the rapidly expanding HIV/VL coinfection.
    • Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial

      Bassat, Quique; Mulenga, Modest; Tinto, Halidou; Piola, Patrice; Borrmann, Steffen; Menéndez, Clara; Nambozi, Michael; Valéa, Innocent; Nabasumba, Carolyn; Sasi, Philip; et al. (2009-11-17)
      BACKGROUND: Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com ISRCTN16263443.
    • Do patents prevent access to drugs for HIV in developing countries?

      Boelaert, M; Lynen, L; Van Damme, W; Colebunders, R (2002-02-20)
    • Drug-Resistant Tuberculosis--Current dilemmas, unanswered questions, challenges, and priority needs

      Zumla, A; Abubakar, I; Raviglione, M; Hoelscher, M; Ditiu, L; McHugh, T D; Squire, S B; Cox, H; Ford, N; McNerney, R; et al. (Oxford University Press, 2012-04-03)
      Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed.
    • 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.
    • Expanding HIV care in Africa: making men matter.

      Mills, E; Ford, N; Mugyenyi, P; Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada V5Z4B4. emills@cfenet.ubc.ca (2009-07-25)
    • Health development versus medical relief: the illusion versus the irrelevance of sustainability.

      Ooms, G; Belgian section of Médecins Sans Frontières. ooms@brussels.msf.org (Public Library of Science, 2006-08)
    • HIV/AIDS prevention and treatment.

      Goemaere, E; Ford, N; Benatar, S R (Elsevier, 2002-07-06)
    • 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.
    • In Resource-Limited Settings Good Early Outcomes Can be Achieved in Children Using Adult Fixed-Dose Combination Antiretroviral Therapy.

      O'Brien, D; Sauvageot, D; Zachariah, R; Humblet, P; AIDS Working Group, Medecins Sans Frontieres, Plantage Middenlaan 14, 1001 EA Amsterdam, The Netherlands. daniel.obrien@amsterdam.msf.org (2006-10-03)
      OBJECTIVES: To (a) determine early treatment outcomes and (b) assess safety in children treated with adult fixed-dose combination (FDC) antiretroviral tablets. SETTING: Sixteen Medecins Sans Frontieres (MSF) HIV programs in eight countries in resource-limited settings (RLS). METHODS: Analysis of routine program data gathered June 2001 to March 2005. RESULTS: A total of 1184 children [median age, 7 years; inter-quartile range (IQR), 4.6-9.3] were treated with antiretroviral therapy (ART) of whom 616(52%) were male. At ART initiation, Centres for Disease Control stages N, A, B and C were 9, 14, 38 and 39%, respectively. Children were followed up for a median period of 6 months (IQR, 2-12 months). At 12 months the median CD4 percentage gain in children aged 18-59 months was 15% (IQR, 6-18%), and the percentage with CD4 gain < 15% was reduced from 85% at baseline to 11%. In those aged 60-156 months, median CD4 cell count gain was 275 cells/microl (IQR, 84-518 cells/microl), and the percentage with CD4 < 200 cells/mul reduced from 51% at baseline to 11%. Treatment outcomes included; 1012 (85%) alive and on ART, 36 (3%) deaths, 15 (1%) stopped ART, 89 (8%) lost to follow-up, and 31 (3%) with unknown outcomes. Overall probability of survival at 12 months was 0.87 (0.84-0.89). Side effects caused a change to alternative antiretroviral drugs in 26 (2%) but no deaths. CONCLUSIONS: Very satisfactory early outcomes can be achieved in children in RLS using generic adult FDC antiretroviral tablets. These findings strongly favour their use as an "interim solution" for scaling-up ART in children; however, more appropriate pediatric antiretroviral drugs remain urgently needed.
    • International nurse migration and HIV/AIDS.

      Lynch, S; Lethola, P; Ford, N (American Medical Association, 2008-09-03)
    • Methodological Issues in the Assessment of Antimalarial Drug Treatment: Analysis of 13 Studies in Eight African Countries from 2001 to 2004.

      Guthmann, J P; Pinoges, L; Checchi, F; Cousens, S; Balkan, S; Van Herp, M; Legros, D; Olliaro, P; Epicentre, 8 rue Saint Sabin, 75011 Paris, France. jguthmann@epicentre.msf.org (Published by American Society for Microbiology, 2006-11)
      The objectives of these analyses were to assess the feasibility of the latest WHO recommendations (28-day follow-up with PCR genotyping) for the assessment of antimalarial drug efficacy in vivo and to examine how different statistical approaches affect results. We used individual-patient data from 13 studies of uncomplicated pediatric falciparum malaria conducted in sub-Saharan Africa, using chloroquine (CQ), sulfadoxine/pyrimethamine (SP), or amodiaquine (AQ). We assessed the use effectiveness and test performance of PCR genotyping in distinguishing recurrent infections. In analyzing data, we compared (i) the risk of failure on target days (days 14 and 28) by using Kaplan-Meier and per-protocol evaluable patient analyses, (ii) PCR-corrected results allowing (method 1) or excluding (method 2) new infections, (iii) and day 14 versus day 28 results. Of the 2,576 patients treated, 2,287 (89%) were evaluable on day 28. Of the 695 recurrences occurring post-day 14, 650 could be processed and 584 were resolved (PCR use effectiveness, 84%; test performance, 90%). The risks of failure on day 28 with Kaplan-Meier and evaluable-patient analyses tended to be generally close (except in smaller studies) because the numbers of dropouts were minimal, but attrition rates on day 28 were higher with the latter method. Method 2 yielded higher risks of failure than method 1. Extending observation to 28 days produced higher estimated risks of failure for SP and AQ but not for CQ (high failure rates by day 14). Results support the implementation of the current WHO protocol and favor analyzing PCR-corrected outcomes by Kaplan-Meier analysis (which allows for dropouts) and retaining new infections (which minimizes losses).
    • Multiple origins and regional dispersal of resistant dhps in African Plasmodium falciparum malaria.

      Pearce, Richard J; Pota, Hirva; Evehe, Marie-Solange B; Bâ, El-Hadj; Mombo-Ngoma, Ghyslain; Malisa, Allen L; Ord, Rosalynn; Inojosa, Walter; Matondo, Alexandre; Diallo, Diadier A; et al. (2009-04-14)
      BACKGROUND: Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution. METHODS AND FINDINGS: We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations. CONCLUSIONS: Resistant dhps has emerged independently in multiple sites in Africa during the past 10-20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.
    • Nutrition outcomes of HIV-infected malnourished adults treated with ready-to-use therapeutic food in sub-Saharan Africa: a longitudinal study.

      Ahoua, Laurence; Umutoni, Chantal; Huerga, Helena; Minetti, Andrea; Szumilin, Elisabeth; Balkan, Suna; Olson, David M; Nicholas, Sarala; Pujades-Rodríguez, Mar; Epicentre, Médecins Sans Frontières, Paris, France. laurence_ahoua@yahoo.fr (BioMed Central home, 2011-01)
      Among people living with HIV/AIDS, nutritional support is increasingly recognized as a critical part of the essential package of care, especially for patients in sub-Saharan Africa. The objectives of the study were to evaluate the outcomes of HIV-positive malnourished adults treated with ready-to-use therapeutic food and to identify factors associated with nutrition programme failure.
    • Observational bias during nutrition surveillance: results of a mixed longitudinal and cross-sectional data collection system in Northern Nigeria.

      Grellety, E; Luquero, F J; Mambula, C; Adamu, H H; Elder, G; Porten, K; Epicentre, Paris, France. Emmanuel.GRELLETY@epicentre.msf.org (PLoS, 2013-10)
      The Sahel is subject to seasonal hungry periods with increasing rates of malnutrition. In Northern Nigeria, there is no surveillance system and surveys are rare. The objectives were to analyse possible observational bias in a sentinel surveillance system using repeated mixed longitudinal/cross-sectional data and estimate the extent of seasonal variation.
    • Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

      Andronikou, S; McHugh, K; Abdurahman, N; Khoury, B; Mngomezulu, V; Brant, W E; Cowan, I; McCulloch, M; Ford, N; Radiology Department, University of Witwatersrand, Johannesburg Gauteng, South Africa; Radiology Department, Great Ormond Street Hospital for Children, London, UK; Radiology Department, University of Cape Town, Cape Town, South Africa; Radiology Department, University of Virginia, Charlottesville, VA, USA; Radiology Department, Christchurch Hospital, Christchurch, New Zealand; Evelyna Children's Hospital, London, UK; Public Health/Access, Medecins Sans Frontieres, Cape Town, South Africa (Springer, 2011-06-09)
      Paediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children.
    • Public health. Getting HIV treatment to the most people.

      Lynch, Sharonann; Ford, Nathan; van Cutsem, Gilles; Bygrave, Helen; Janssens, Bart; Decroo, Tom; Andrieux-Meyer, Isabelle; Roberts, Teri; Balkan, Suna; Casas, Esther; et al. (2012-07-20)
    • Public Health. The cholera crisis in Africa.

      Bhattacharya, S; Black, R; Bourgeois, L; Clemens, J; Cravioto, A; Deen, J L; Dougan, Gordon; Glass, R; Grais, R F; Greco, M; et al. (2009-05-15)
    • 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)