• Safe Water for the Aral Sea Area: Could it get Any Worse?

      Small, I; Falzon, D; van der Meer, J; Ford, N; Médecins Sans Frontières, Aral Sea Programme, Tashkent, Uzbekistan. (Published by Oxford University Press, 2003-03)
      The environmental adversities around the Aral Sea in Central Asia have been the subject of recent research. Attempts at sustainable provision of palatable drinking water in low chemical and microbial contaminants for the 4 million people in the two countries around the Aral littoral have been largely unsuccessful. In the last few years, severe drought has further depleted the amount of available water. This shortage has negatively impacted on agriculture, and accentuated the out migration of people. An appeal is made to assist the local population in this arid area to cope with the acute and chronic deterioration of water security.
    • Safety and Effectiveness of Amphotericin B Deoxycholate for the Treatment of Visceral Leishmaniasis in Uganda.

      Mueller, Y; Nguimfack, A; Cavailler, P; Couffignal, S; Rwakimari, J B; Loutan, L; Chappuis, F; Médecins Sans Frontières, Swiss Section, Rue de Lausanne 78, 1202 Geneva, Switzerland. yolanda.mueller@freesurf.ch (Maney Publishing, 2008-01)
      Between September 2003 and April 2004, the supply of antimonial drugs to Amudat Hospital, in north-eastern Uganda, was interrupted and all cases of visceral leishmaniasis presenting at the hospital could only be treated with amphotericin B deoxycholate (AmB). This allowed the safety and effectiveness of the AmB to be evaluated, in comparison with an historical cohort of patients treated, at the same hospital, with meglumine antimoniate (Sb(V)). Demographic and clinical data were collected before and after treatment. Adverse effects were recorded passively in all the subjects, and actively, using a standardized questionnaire, in a sub-group of the patients given AmB. The in hospital case-fatality 'rates' were 4.8% [95% confidence interval (CI) = 2.4%-8.8%] among the 210 patients treated with AmB and 3.7% (CI = 1.4%-7.9%) among the 161 patients treated with Sb(V) (P>0.20). Adverse effects requiring treatment interruption were rare in both cohorts. Treatment failures (i.e. non-responses or relapses) were observed in 2.9% (CI = 1.2%-6.4%) of the patients treated with AmB and 1.2% (CI = 0.1%-4.4%) of the patients treated with Sb(V) (P>0.20). For the treatment of visceral leishmaniasis in Uganda, AmB therefore had a similar effectiveness and safety profile to that of meglumine antimoniate.
    • 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.
    • Safety and effectiveness of short-course AmBisome in the treatment of Post-Kala-azar Dermal Leishmaniasis (PKDL): a prospective cohort study in Bangladesh

      den Boer, M; Das, Asish K; Akhter, F; Burza, S; Ramesh, V; Ahmed, BN; Zijlstra, EE; Ritmeijer, K (Oxford University Press, 2018-03-15)
      A safe and effective short-course treatment regimen for Post Kala Azar Dermal Leishmaniasis (PKDL) is considered essential for achieving and sustaining elimination of visceral leishmaniasis (VL) in the Indian subcontinent.(1, 2) Here, single dose liposomal amphotericin B (AmBisome) has been adopted as a first line regimen for VL; however the effectiveness and safety of AmBisome for PKDL has not been formally evaluated.
    • Safety and Effectiveness of Sodium Stibogluconate and Paromomycin Combination for the Treatment of Visceral Leishmaniasis in Eastern Africa: Results from a Pharmacovigilance Programme

      Kimutai, R; Musa, AM; Njoroge, S; Omollo, R; Alves, F; Hailu, A; Khalil, EAG; Diro, E; Soipei, P; Musa, B; et al. (Springer Link, 2017-01-09)
      In 2010, WHO recommended a new first-line treatment for visceral leishmaniasis (VL) in Eastern Africa. The new treatment, a combination of intravenous (IV) or intramuscular (IM) sodium stibogluconate (SSG) and IM paromomycin (PM) was an improvement over SSG monotherapy, the previous first-line VL treatment in the region. To monitor the new treatment's safety and effectiveness in routine clinical practice a pharmacovigilance (PV) programme was developed.
    • Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis.

      Zwang, Julien; Ashley, Elizabeth A; Karema, Corine; D'Alessandro, Umberto; Smithuis, Frank; Dorsey, Grant; Janssens, Bart; Mayxay, Mayfong; Newton, Paul; Singhasivanon, Pratap; et al. (2009-07-15)
      BACKGROUND: The fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP) is a promising new artemisinin-based combination therapy (ACT). We present an individual patient data analysis of efficacy and tolerability in acute uncomplicated falciparum malaria, from seven published randomized clinical trials conducted in Africa and South East Asia using a predefined in-vivo protocol. Comparator drugs were mefloquine-artesunate (MAS3) in Thailand, Myanmar, Laos and Cambodia; artemether-lumefantrine in Uganda; and amodiaquine+sulfadoxine-pyrimethamine and artesunate+amodiaquine in Rwanda. METHODS AND FINDINGS: In total 3,547 patients were enrolled: 1,814 patients (32% children under five years) received DP and 1,733 received a comparator antimalarial at 12 different sites and were followed for 28-63 days. There was no significant heterogeneity between trials. DP was well tolerated with 1.7% early vomiting. There were less adverse events with DP in children and adults compared to MAS3 except for diarrhea; ORs (95%CI) 2.74 (2.13 to 3.51) and 3.11 (2.31 to 4.18), respectively. DP treatment resulted in a rapid clearance of fever and parasitaemia. The PCR genotype corrected efficacy at Day 28 of DP assessed by survival analysis was 98.7% (95%CI 97.6-99.8). DP was superior to the comparator drugs in protecting against both P.falciparum recurrence and recrudescence (P = 0.001, weighted by site). There was no difference between DP and MAS3 in treating P. vivax co-infections and in suppressing the first relapse (median interval to P. vivax recurrence: 6 weeks). Children under 5 y were at higher risk of recurrence for both infections. The proportion of patients developing gametocytaemia (P = 0.002, weighted by site) and the subsequent gametocyte carriage rates were higher with DP (11/1000 person gametocyte week, PGW) than MAS3 (6/1000 PGW, P = 0.001, weighted by site). CONCLUSIONS: DP proved a safe, well tolerated, and highly effective treatment of P.falciparum malaria in Asia and Africa, but the effect on gametocyte carriage was inferior to that of MAS3.
    • Safety of a heat-stable rotavirus vaccine among children in Niger: Data from a phase 3, randomized, double-blind, placebo-controlled trial

      Coldiron, ME; Guindo, O; Makarimi, R; Soumana, I; Matar Seck, A; Garba, S; Macher, E; Isanaka, S; Grais, RF (Elsevier, 2018-05-08)
      Rotavirus remains a major cause of diarrhea among children under 5 years of age. The efficacy of RotaSIIL, a pentavalent rotavirus vaccine, was shown in an event-driven trial in Niger. We describe the two-year safety follow-up of this trial.
    • Safety of efavirenz in first-trimester of pregnancy: a systematic review and meta-analysis of outcomes from observational cohorts.

      Ford, Nathan; Mofenson, Lynne; Kranzer, Katharina; Medu, Lanre; Frigati, Lisa; Mills, Edward J; Calmy, Alexandra; Médecins Sans Frontières, South Africa Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa cPediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA dLondon School of Hygiene and Tropical Medicine, London, UK eFaculty of Health Sciences, Simon Fraser University, Vancouver, Canada fRed Cross Children's hospital, Cape Town, South Africa gFaculty of Health Sciences, University of Ottawa, Canada hGeneva University Hospital, HIV Unit, Service of Infectious Diseases, Geneva, Switzerland. (2010-05-14)
      INTRODUCTION
    • Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis

      Ford, Nathan; Calmy, Alexandra; Mofenson, Lynne; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; Médecins Sans Frontières, Geneva, Switzerland; Geneva University Hospital, HIV Unit, Service of Infectious Diseases, Geneva, Switzerland; Pediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA (Lippincott Williams & Wilkins, 2011-11-28)
      Evidence of the risk of birth defects with efavirenz use is limited. We updated a meta-analysis of birth defects in infants with first trimester efavirenz exposure up to July 2011. In 21 studies, there were 39 defects among live births in 1437 women receiving first trimester efavirenz [2.0%, 95% confidence interval (CI) 0.82-3.18]. The relative risk of defects comparing women on efavirenz-based (1290 live births) and nonefavirenz-based regimens (8122 live births) was 0.85 (95% CI 0.61-1.20). One neural tube defect was observed (myelomeningocele), giving an incidence of 0.07% (95% CI 0.002-0.39).
    • Safety of the rVSV ZEBOV vaccine against Ebola Zaire among frontline workers in Guinea

      Juan-Giner, A; Tchaton, M; Jemmy, JP; Soumah, A; Boum, Y; Faga, EM; Cisse, M; Grais, RF (Elsevier, 2018-09-25)
      As part of the ring vaccination trial in Guinea, Front Line Workers were invited to participate in a sub-study to provide additional information on the immunogenicity and safety of rVSVΔG/ZEBOV-GP. Here we summarize the information on the safety follow-up.
    • Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.

      Ford, Nathan; Lee, Janice; Andrieux-Meyer, Isabelle; Calmy, Alexandra; Médecins Sans Frontières, Geneva, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; Service of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland (DovePress, 2011-04-28)
      The vast majority of people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome reside in the developing world, in settings characterized by limited health budgets, critical shortages of doctors, limited laboratory monitoring, a substantial burden of HIV in children, and high rates of coinfection, in particular tuberculosis. Therefore, the extent to which new antiretrovirals will contribute to improvements in the management of HIV globally will depend to a large extent on their affordability, ease of use, low toxicity profile, availability as pediatric formulations, and compatibility with tuberculosis and other common drugs. We undertook a systematic review of the available evidence regarding drug interactions, and the efficacy and safety of rilpivirine (also known as TMC-278), and assessed our findings in view of the needs and constraints of resource-limited settings. The main pharmacokinetic interactions relevant to HIV management reported to date include reduced bioavailability of rilpivirine when coadministered with rifampicin, rifabutin or acid suppressing agents, and reduced bioavailability of ketoconazole. Potential recommendations for dose adjustment to compensate for these interactions have not been elaborated. Trials comparing rilpivirine and efavirenz found similar outcomes up to 96 weeks in intent-to-treat analysis; failure of rilpivirine was mainly virological, whereas failure among those exposed to efavirenz was mainly related to the occurrence of adverse events. Around half of the patients who fail rilpivirine develop non-nucleoside reverse transcriptase inhibitor resistance mutations. The incidence of Grade 2-4 events was lower for rilpivirine compared with efavirenz. Grade 3-4 adverse events potentially related to the drugs were infrequent and statistically similar for both drugs. No dose-response relationship was observed for efficacy or safety, and the lowest dose (25 mg) was selected for further clinical development. The potential low cost and dose of the active pharmaceutical ingredient means that rilpivirine can potentially be manufactured at a low price. Moreover, its long half-life suggests the potential for monthly dosing via nonoral routes, with promising early results from studies of a long-acting injectable formulation. These characteristics make rilpivirine an attractive drug for resource-limited settings. Future research should assess the potential to improve robustness and assess the clinical significance of interaction with antituberculosis drugs.
    • Safety, Feasibility, and Acceptability of the PrePex Device for Adult Male Circumcision in Malawi

      Kohler, PK; Tippett Barr, BA; Kangʼombe, A; Hofstee, C; Kilembe, F; Galagan, S; Chilongozi, D; Namate, D; Machaya, M; Kabwere, K; et al. (Lippincott Williams & Wilkins, 2016-06-01)
      Nonsurgical adult male circumcision devices present an alternative to surgery where health resources are limited. This study aimed to assess the safety, feasibility, and acceptability of the PrePex device for adult male circumcision in Malawi.
    • SAMBA HIV semi-quantitative test, a new point-of-care viral load monitoring assay for resource-limited settings

      Ritchie, Allyson V; Ushiro-Lumb, Ines; Edemaga, Daniel; Joshi, Hrishikesh A; De Ruiter, Annemiek; Szumilin, Elisabeth; Jendrulek, Isabelle; McGuire, Megan; Goel, Neha; Sharma, Pia I; et al. (2014-07-16)
      Routine viral load (VL) testing of HIV-infected individuals on antiretroviral therapy (ART) is used to monitor treatment efficacy. However, due to logistical challenges, implementation of VL has been difficult in resource-limited settings. The aim of this study was to evaluate the performance of the SAMBA Semi-Q Test in London, Malawi, and Uganda. The SAMBA HIV-1 Semi-Q Test can distinguish between patients with VL above or below 1000 copies/ml. The SAMBA Semi-Q was validated with diluted clinical samples and blinded plasma samples collected from HIV-1-positive individuals. SAMBA Semi-Q results were compared with results from the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test v2.0. Testing of 96 2-10 fold dilutions of four samples containing HIV-1 subtype C as well as 488 samples from patients in the United Kingdom, Malawi, and Uganda, respectively, yielded an overall accuracy for SAMBA Semi-Q of 99% (95% CI 93.8 - 99.9%) and 96.9% (95% CI 94.9 - 98.3%) respectively compared to Roche. Analysis of VL data from patients in Malawi and Uganda showed that the SAMBA cut-off of 1000 copies/ml appropriately distinguished treated from untreated individuals. Furthermore, analysis of the viral load of 232 patients on ART in Malawi and Uganda revealed similar patterns for virological control defined as either <1000 copies/ml (SAMBA cut-off) or <5000 copies/ml (WHO 2010 criterion). This study suggests that SAMBA Semi-Q has adequate concurrency with the gold standard measurements for viral load measurement. This test can allow VL monitoring of patients on ART at the point of care in resource-limited settings.
    • SARS and Carlo Urbani.

      Reilley, B; Van Herp, M; Sermand, D; Dentico, N; Médecins sans Frontières, USA. (Massachusetts Medical Society, 2003-05-15)
    • Saving life and limb: limb salvage using external fixation, a multi-centre review of orthopaedic surgical activities in Médecins Sans Frontières

      Bertol, M J; Van den Bergh, R; Trelles Centurion, M; Kenslor Ralph D, H; Basimuoneye Kahutsi, J-P; Qayeum Qasemy, A; Jean, J; Majuste, A; Kubuya Hangi, T; Safi, S (Springer Berlin Heidelberg, 2014-07-20)
      While the orthopaedic management of open fractures has been well-documented in developed settings, limited evidence exists on the surgical outcomes of open fractures in terms of limb salvage in low- and middle-income countries. We therefore reviewed the Médecins Sans Frontières-Operational Centre Brussels (MSF-OCB) orthopaedic surgical activities in the aftermath of the 2010 Haiti earthquake and in three non-emergency projects to assess the limb salvage rates in humanitarian contexts in relation to surgical staff skills.
    • Saving the World, or Saving One Life at a Time?

      Delaunay, S (Springer, 2016-01-11)
    • Scale-Up of ART in Malawi Has Reduced Case Notification Rates in HIV-Positive and HIV-Negative Tuberculosis

      Kanyerere, H; Girma, B; Mpunga, J; Tayler-Smith, K; Harries, A D; Jahn, A; Chimbwandira, FM (International Union Against Tuberculosis and Lung Disease, 2016-12-21)
      Setting: For 30 years, Malawi has experienced a dual epidemic of human immunodeficiency virus (HIV) infection and tuberculosis (TB) that has recently begun to be attenuated by the scale-up of antiretroviral therapy (ART). Objective: To report on the correlation between ART scale-up and annual national TB case notification rates (CNR) in Malawi, stratified by HIV-positive and HIV-negative status, from 2005 to 2015. Design: A retrospective descriptive ecological study using aggregate data from national reports. Results: From 2005 to 2015, ART was scaled up in Malawi from 28 470 to 618 488 total patients, with population coverage increasing from 2.4% to 52.2%. During this time, annual TB notifications declined by 35%, from 26 344 to 17 104, and the TB CNR per 100 000 population declined by 49%, from 206 to 105. HIV testing uptake increased from 51% to 92%. In known HIV-positive TB patients, the CNR decreased from a high of 1247/100 000 to 710/100 000, a 43% decrease. In known HIV-negative TB patients, the CNR also decreased, from a high of 66/100 000 to 49/100 000, a 26% decrease. Conclusion: TB case notifications have continued to decline in association with ART scale-up, with the decline seen more in HIV-positive than HIV-negative TB. These findings have programmatic implications for national TB control efforts.
    • Scale-up of Routine Viral Load Testing in Resource-Poor Settings: Current and Future Implementation Challenges

      Roberts, T; Cohn, J; Bonner, K; Hargreaves, S (Oxford University Press, 2016-04-15)
      Despite immense progress in antiretroviral therapy (ART) scale-up, many people still lack access to basic standards of care, with our ability to meet the Joint United Nations Programme on HIV/AIDS 90-90-90 treatment targets for HIV/AIDS dependent on dramatic improvements in diagnostics. The World Health Organization recommends routine monitoring of ART effectiveness using viral load (VL) testing at 6 months and every 12 months, to monitor treatment adherence and minimize failure, and will publish its VL toolkit later this year. However, the cost and complexity of VL is preventing scale-up beyond developed countries and there is a lack of awareness among clinicians as to the long-term patient benefits and its role in prolonging the longevity of treatment programs. With developments in this diagnostic field rapidly evolving-including the recent improvements for accurately using dried blood spots and the imminent appearance to the market of point-of-care technologies offering decentralized diagnosis-we describe current barriers to VL testing in resource-limited settings. Effective scale-up can be achieved through health system and laboratory system strengthening and test price reductions, as well as tackling multiple programmatic and funding challenges.
    • Scaling up antiretroviral therapy in Malawi-implications for managing other chronic diseases in resource-limited countries.

      Harries, A D; Zachariah, R; Jahn, A; Schouten, E J; Kamoto, K; International Union against Tuberculosis and Lung Disease, Paris, France. adharries@theunion.org (2009-11-01)
      The national scale-up of antiretroviral therapy (ART) in Malawi is based on the public health approach, with principles and practices borrowed from the successful DOTS (directly observed treatment, short course) tuberculosis control framework. The key principles include political commitment, free care, and standardized systems for case finding, treatment, recording and reporting, and drug procurement. Scale-up of ART started in June 2004, and by December 2008, 223,437 patients were registered for treatment within a health system that is severely underresourced. The Malawi model for delivering lifelong ART can be adapted and used for managing patients with chronic noncommunicable diseases, the burden of which is already high and continues to grow in low-income and middle-income countries. This article discusses how the principles behind the successful Malawi model of ART delivery can be applied to the management of other chronic diseases in resource-limited settings and how this paradigm can be used for health systems strengthening.