• The G8 and access to medicines: no more broken promises.

      Moran, M; Ford, N; Médecins Sans Frontières, EC1N 8QX, London, UK. (Elsevier, 2003-05-10)
    • Gender differences in immune reconstitution: a multicentric cohort analysis in sub-saharan Africa

      Maman, David; Pujades-Rodriguez, Mar; Subtil, Fabien; Pinoges, Loretxu; McGuire, Megan; Ecochard, Rene; Etard, Jean-François; Epicentre, Médecins Sans Frontières, Paris, France; Hospices Civils de Lyon, Service de Biostatistique, Lyon, France; TransVIHMI, Montpellier, France; Université de Lyon, Lyon, France; Université Lyon I, Villeurbanne, France; 6 Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique Santé, Pierre-Bénite, France (Public Library of Science (PLoS), 2012-02-17)
      In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution.
    • Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study.

      Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh F; et al. (2012-09)
      Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.
    • General surgeons: a dying breed?

      Chu, K; South African Medical Unit, Médecins Sans Frontières, 49 Jorissen St, Braamfontein 2017, Johannesburg, South Africa. kathryn.chu@joburg.msf.org (American Medical Association, 2009-06)
    • Generic Fixed-Dose Combination Antiretroviral Treatment in Resource-Poor Settings: Multicentric Observational Cohort

      Calmy, A; Pinoges, L; Szumilin, E; Zachariah, R; Ford, N; Ferradini, L; MSF, Campaign for Access to Essential Medicines, 78 rue de Lausanne, 1205 Geneva, Switzerland. acalmy@stvincents.com.au (2006-05-12)
      BACKGROUND: The use fixed-dose combination (FDC) is a critical tool in improving HAART. Studies on the effectiveness of combined lamivudine, stavudine and nevirapine (3TC/d4T/NVP) are scarce. OBJECTIVE: To analyse 6861 patients in a large observational cohort from 21 Médecins Sans Frontieres (MSF) HIV/AIDS programmes taking 3TC/d4T/NVP, with subcohort analyses of patients at 12 and 18 months of treatment. METHODS: Survival was analysed using Kaplan-Meier method and factors associated with progression to death with Cox proportional hazard ratio. RESULTS: Median baseline CD4 cell count at initiating of FDC was 89 cells/microl [interquartile range (IQR), 33-158]. The median follow-up time was 4.1 months (IQR, 1.9-7.3). The incidence rate of death during follow-up was 14.2/100 person-years [95% confidence interval (CI), 13.8-14.5]. Estimates of survival (excluding those lost to follow-up) were 0.93 (95% CI, 92-94) at 6 months (n = 2,231) and 0.90 (95% CI, 89-91) at 12 months (n = 472). Using a Cox model, the following factors were associated with death: male gender, symptomatic infection, body mass index < 18 kg/m and CD4 cell count 15-50 cells/microl or < 15 cells/microl. Subcohort analysis of 655 patients after 1 year of follow-up (M12 FDC cohort) revealed that 77% remained on HAART, 91% of these still on the FDC regimen; 5% discontinued the FDC because of drug intolerance. At 18 months, 77% of the patients remained on HAART. CONCLUSIONS: Positive outcomes for d4T/3TC/NVP are reported for up to 18 months in terms of efficacy and safety.
    • Generic medicines are not substandard medicines.

      Ford, N; 't Hoen, E (Elsevier, 2002-04-13)
    • Genetic heterogeneity of hepatitis E virus in Darfur, Sudan, and neighboring Chad.

      Nicand, E; Armstrong, G L; Enouf, V; Guthmann, J P; Guerin, J P; Caron, M; Nizou, J Y; Andraghetti, R; National Reference Centre for Hepatitis E, Teaching Military Hospital Val de Grâce, Paris, France. en.biol-vdg@filnet.fr (2005-12)
      The within-outbreak diversity of hepatitis E virus (HEV) was studied during the outbreak of hepatitis E that occurred in Sudan in 2004. Specimens were collected from internally displaced persons living in a Sudanese refugee camp and two camps implanted in Chad. A comparison of the sequences in the ORF2 region of 23 Sudanese isolates and five HEV samples from the two Chadian camps displayed a high similarity (>99.7%) to strains belonging to Genotype 1. But four isolates collected in one of the Chadian camps were close to Genotype 2. Circulation of divergent strains argues for possible multiple sources of infection.
    • GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India

      Isaakidis, P; Ferlazzo, G; Das, M; Pasupuleti, D; Sloan, S; Hossain, F; Kalon, S; Mansoor, H; Rao, S (MDPI AG, 2019-12-21)
      Abstract: Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
    • GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India.

      Das, M; Pasupuleti, D; Rao, S; Sloan, S; Mansoor, H; Kalon, S; Hossain, F; Ferlazzo, G; Isaakidis, P (MDPI AG, 2019-12-21)
      Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
    • Genomic History of the seventh Pandemic of Cholera in Africa

      Weill, FX; Domman, D; Njamkepo, E; Tarr, C; Rauzier, J; Fawal, N; Keddy, KH; Salje, H; Moore, S; Mukhopadhyay, AK; et al. (American Association for the Advancement of Science, 2017-11-10)
      The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa.
    • Genomic Insights into the 2016-2017 Cholera Epidemic in Yemen

      Weill, FX; Domman, D; Njamkepo, E; Almesbahi, AA; Naji, M; Nasher, SS; Rakesh, A; Assiri, AM; Sharma, NC; Kariuki, S; et al. (Nature Publishing Group, 2019-01-02)
      Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.
    • Genotyping and outcomes of presumptive second line ART failure cases switched to third line or maintained on second line ART in Mumbai, India

      Gill, N; Van den Bergh, R; Wut Yee Kyaw, K; Laxmeshwar, C; Das, M; Rastogi, S; Mansoor, H; Kalon, S; Isaakidis, P; Arago Galindo, M (2019-11-21)
      BACKGROUND: HIV programs are increasingly confronted with failing antiretroviral therapy (ART), including second-line regimens. WHO has provided guidelines on switching to third-line ART. In a Médecins Sans Frontières clinic in Mumbai, India, receiving referred presumptive second-line ART failure cases, an evidence-based protocol consisting of viral load (VL) testing, enhanced adherence counselling (EAC) and genotype for switching was implemented. OBJECTIVE: To document the outcome and genotype of presumptive second-line ART failure cases switched to third-line or maintained on second-line ART. DESIGN: Retrospective cohort study of patients referred between January 2011 and September 2017. RESULTS: The cases (n = 120) were complex with median 9.2 years of ART exposure, poor adherence at baseline, and exposure to multiple ART regimens other than recommended by WHO. Out of 90 evaluated cases, 39(43%) were maintained on second-line ART. Forty-nine (54%) were ever switched to third-line ART. Twelve months virological suppression was 72% in the second-line and 93% in the third-line ART cohort, while retention in care was 80% and 94% respectively. Genotyping showed 62% resistance for PIs, and 52% triple class resistance to NRTIs, NNRTIs and PIs. Resistance was noted for the new class of integrase inhibitors, and for different drugs without any documented previous exposure to the same drug. CONCLUSION: Adopting WHO guidelines on switching ART regimens and provision of EAC can prevent unnecessary switching/exposure to third-line ART regimens. Genotyping is urgently required in national HIV programs, which currently use only the exposure history of patients for switching to third-line ART regimens.
    • Geographic Distribution and Mortality Risk Factors during the Cholera Outbreak in a Rural Region of Haiti, 2010-2011

      Page, Anne-Laure; Ciglenecki, Iza; Jasmin, Ernest Robert; Desvignes, Laurence; Grandesso, Francesco; Polonsky, Jonathan; Nicholas, Sarala; Alberti, Kathryn P; Porten, Klaudia; Luquero, Francisco J (Public Library of Science, 2015-03-26)
      In 2010 and 2011, Haiti was heavily affected by a large cholera outbreak that spread throughout the country. Although national health structure-based cholera surveillance was rapidly initiated, a substantial number of community cases might have been missed, particularly in remote areas. We conducted a community-based survey in a large rural, mountainous area across four districts of the Nord department including areas with good versus poor accessibility by road, and rapid versus delayed response to the outbreak to document the true cholera burden and assess geographic distribution and risk factors for cholera mortality.
    • Geographical distribution of selected and putatively neutral SNPs in Southeast Asian malaria parasites.

      Anderson, T J C; Nair, S; Sudimack, D; Williams, J T; Mayxay, M; Newton, P N; Guthmann, J P; Smithuis, F M; Tran, T H; van den Broek, I; et al. (2005-12)
      Loci targeted by directional selection are expected to show elevated geographical population structure relative to neutral loci, and a flurry of recent papers have used this rationale to search for genome regions involved in adaptation. Studies of functional mutations that are known to be under selection are particularly useful for assessing the utility of this approach. Antimalarial drug treatment regimes vary considerably between countries in Southeast Asia selecting for local adaptation at parasite loci underlying resistance. We compared the population structure revealed by 10 nonsynonymous mutations (nonsynonymous single-nucleotide polymorphisms [nsSNPs]) in four loci that are known to be involved in antimalarial drug resistance, with patterns revealed by 10 synonymous mutations (synonymous single-nucleotide polymorphisms [sSNPs]) in housekeeping genes or genes of unknown function in 755 Plasmodium falciparum infections collected from 13 populations in six Southeast Asian countries. Allele frequencies at known nsSNPs underlying resistance varied markedly between locations (F(ST) = 0.18-0.66), with the highest frequencies on the Thailand-Burma border and the lowest frequencies in neighboring Lao PDR. In contrast, we found weak but significant geographic structure (F(ST) = 0-0.14) for 8 of 10 sSNPs. Importantly, all 10 nsSNPs showed significantly higher F(ST) (P < 8 x 10(-5)) than simulated neutral expectations based on observed F(ST) values in the putatively neutral sSNPs. This result was unaffected by the methods used to estimate allele frequencies or the number of populations used in the simulations. Given that dense single-nucleotide polymorphism (SNP) maps and rapid SNP assay methods are now available for P. falciparum, comparing genetic differentiation across the genome may provide a valuable aid to identifying parasite loci underlying local adaptation to drug treatment regimes or other selective forces. However, the high proportion of polymorphic sites that appear to be under balancing selection (or linked to selected sites) in the P. falciparum genome violates the central assumption that selected sites are rare, which complicates identification of outlier loci, and suggests that caution is needed when using this approach.
    • Geographical Variation in the Response of Visceral Leishmaniasis to Paromomycin in East Africa: A Multicentre, Open-Label, Randomized Trial

      Hailu, Asrat; Musa, Ahmed; Wasunna, Monique; Balasegaram, Manica; Yifru, Sisay; Mengistu, Getahun; Hurissa, Zewdu; Hailu, Workagegnehu; Weldegebreal, Teklu; Tesfaye, Samson; et al. (2010-10-26)
      Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India.
    • Getting it right for children: improving tuberculosis treatment access and new treatment options

      Brigden, Grania; Furin, Jennifer; Van Gulik, Clara; Marais, Ben (Informa Healthcare/Expert Reviews - We regret that this article is behind a paywall., 2015-03-05)
      Children were often the forgotten victims of the global tuberculosis (TB) epidemic, neglected by traditional TB services as well as maternal and child health initiatives. Luckily this is changing with a greater focus on children and the issues regarding their optimal management. A common misconception is that children with TB are always difficult to diagnose and treat. New diagnostic tools are urgently needed, but most children with TB in high-burden settings can be diagnosed with available approaches and treatment outcomes are generally excellent. Increased TB awareness, appropriate training of health care workers and inclusion in integrated management of childhood illness strategies will improve the access and quality of care that children receive. This review highlights what needs to be done to ensure that no child unnecessarily dies from TB and provides a brief overview of new advances in the field.
    • A Global Biomedical R&D Fund and Mechanism for Innovations of Public Health Importance

      Balasegaram, Manica; Bréchot, Christian; Farrar, Jeremy; Heymann, David; Ganguly, Nirmal; Khor, Martin; Lévy, Yves; Matsoso, Precious; Minghui, Ren; Pécoul, Bernard; et al. (Public Library of Science, 2015-05-11)
      Bernard Pécoul and colleagues call for the establishment of a global biomedical R&D fund as a key priority of the G7 summit in June 2015.
    • Global Burden of Rheumatic Heart Disease

      Rossi, G (Massachusetts Medical Society, 2018-01-04)
    • Global epidemiology of invasive meningococcal disease

      Jafri, Rabab Z; Ali, Asad; Messonnier, Nancy E; Tevi-Benissan, Carol; Durrheim, David; Eskola, Juhani; Fermon, Florence; Klugman, Keith P; Ramsay, Mary; Sow, Samba; et al. (BioMed Central, 2013-09-10)
      Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made.
    • A global framework for action to improve the primary care response to chronic non-communicable diseases: a solution to a neglected problem.

      Maher, D; Harries, A D; Zachariah, R; Enarson, D (2009-09-22)
      BACKGROUND: Although in developing countries the burden of morbidity and mortality due to infectious diseases has often overshadowed that due to chronic non-communicable diseases (NCDs), there is evidence now of a shift of attention to NCDs. DISCUSSION: Decreasing the chronic NCD burden requires a two-pronged approach: implementation of the multisectoral policies aimed at decreasing population-level risks for NCDs, and effective and affordable delivery of primary care interventions for patients with chronic NCDs. The primary care response to common NCDs is often unstructured and inadequate. We therefore propose a programmatic, standardized approach to the delivery of primary care interventions for patients with NCDs, with a focus on hypertension, diabetes mellitus, chronic airflow obstruction, and obesity. The benefits of this approach will extend to patients with related conditions, e.g. those with chronic kidney disease caused by hypertension or diabetes. This framework for a "public health approach" is informed by experience of scaling up interventions for chronic infectious diseases (tuberculosis and HIV). The lessons learned from progress in rolling out these interventions include the importance of gaining political commitment, developing a robust strategy, delivering standardised interventions, and ensuring rigorous monitoring and evaluation of progress towards defined targets. The goal of the framework is to reduce the burden of morbidity, disability and premature mortality related to NCDs through a primary care strategy which has three elements: 1) identify and address modifiable risk factors, 2) screen for common NCDs and 3) and diagnose, treat and follow-up patients with common NCDs using standard protocols. The proposed framework for NCDs borrows the same elements as those developed for tuberculosis control, comprising a goal, strategy and targets for NCD control, a package of interventions for quality care, key operations for national implementation of these interventions (political commitment, case-finding among people attending primary care services, standardised diagnostic and treatment protocols, regular drug supply, and systematic monitoring and evaluation), and indicators to measure progress towards increasing the impact of primary care interventions on chronic NCDs. The framework needs evaluation, then adaptation in different settings. SUMMARY: A framework for a programmatic "public health approach" has the potential to improve on the current unstructured approach to primary care of people with chronic NCDs. Research to establish the cost, value and feasibility of implementing the framework will pave the way for international support to extend the benefit of this approach to the millions of people worldwide with chronic NCDs.