• Accelerating the Elimination of Viral Hepatitis: a Lancet Gastroenterology & Hepatology Commission.

      Cooke, GS; Andrieux-Meyer, I; Applegate, TL; Atun, R; Burry, JR; Cheinquer, H; Dusheiko, G; Feld, JJ; Gore, C; Griswold, MG; et al. (Elsevier, 2019-02-01)
      Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.
    • Antibiotic Resistance in West Africa: A Systematic Review and Meta-Analysis

      Bernabé, K; Langendorf, C; Ford, N; Ronat, J; Murphy, R (Elsevier, 2017-07-01)
      Growing data suggest that antibiotic-resistant bacterial infections are common in low and middle-income countries. This review summarizes the microbiology of key bacterial syndromes encountered in West Africa and estimates the prevalence of antimicrobial resistance (AMR) that could compromise first-line empirical treatment.
    • Beauty and the beast.

      Cox, H; Isles, S; Médecins Sans Frontières, 7 Ganges Street, Maitama, Abuja, Nigeria. helenscox@yahoo.com.au (Elsevier, 2003-01)
    • Behavioural characteristics, prevalence of Chlamydia trachomatis and antibiotic susceptibility of Neisseria gonorrhoeae in men with urethral discharge in Thyolo, Malawi.

      Zachariah, R; Harries, A D; Nkhoma, W; Arendt, V; Nchingula, D; Chantulo, A; Chimtulo, F; Kirpach, P; Médecins sans Frontières-Luxembourg, Thyolo District, Malawi. zachariah@internet.lu (Elsevier, 2008-01-25)
      A study was carried out in 2000/2001 in a rural district of Malawi among men presenting with urethral discharge, in order to (a) describe their health-seeking and sexual behaviour, (b) determine the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis, and (c) verify the antibiotic susceptibility of N. gonorrhoeae. A total of 114 patients were entered into the study; 61% reported having taken some form of medication before coming to the sexually transmitted infections clinic. The most frequent alternative source of care was traditional healers. Sixty-eight (60%) patients reported sexual encounters during the symptomatic period, the majority (84%) not using condoms. Using ligase chain reaction on urine, N. gonorrhoeae was detected in 91 (80%) and C. trachomatis in 2 (2%) urine specimens. Forty five of 47 N. gonorrhoeae isolates produced penicillinase, 89% showing multi-antimicrobial resistance. This study emphasizes the need to integrate alternative care providers and particularly traditional healers in control activities, and to encourage their role in promoting safer sexual behaviour. In patients presenting with urethral discharge in our rural setting, C. trachomatis was not found to be a major pathogen. Antimicrobial susceptibility surveillance of N. gonorrhoeae is essential in order to prevent treatment failures and control the spread of resistant strains.
    • 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.
    • Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study.

      Nathan, N; Borel, T; Djibo, A; Evans, D; Djibo, S; Corty, J F; Guillerm, M; Alberti, K P; Pinoges, L; Guerin, P J; et al. (Elsevier, 2008-04-14)
      BACKGROUND: In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis. METHODS: In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses. FINDINGS: Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported. INTERPRETATION: Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.
    • Cholera epidemic in Yemen – Author's reply

      Camacho, A; Bouhenia, M; Azman, AS; Poncin, M; Zagaria, N; Luquero, FJ (Elsevier, 2018-10-10)
    • Cholera epidemic in Yemen, 2016-18: an analysis of surveillance data

      Camacho, A; Bouhenia, M; Alyusfi, R; Alkohlani, A; Naji, MAM; de Radiguès, X; Abubakar, AM; Almoalmi, A; Seguin, C; Sagrado, MJ; et al. (Elsevier, 2018-05-03)
      In war-torn Yemen, reports of confirmed cholera started in late September, 2016. The disease continues to plague Yemen today in what has become the largest documented cholera epidemic of modern times. We aimed to describe the key epidemiological features of this epidemic, including the drivers of cholera transmission during the outbreak.
    • Cholera outbreak during massive influx of Rwandan returnees in November 1996

      Brown, V; Reilley, B; Ferrir, M C; Gabaldon, J; Manoncourt, S (Elsevier, 1997-01)
    • Cholera outbreak during massive influx of Rwandan returnees in November, 1996.

      Brown, V; Reilley, B; Ferrir, M; Gabaldon, J; Manoncourt, S (Elsevier, 1997-01-18)
    • Clinical Profile and Containment of Ebola Virus Disease Outbreak in Two Large West African Cities, Nigeria, July-September, 2014

      Ohuabunwo, C; Ameh, C; Oduyebo, O; Ahumibe, A; Mutiu, B; Olayinka, A; Gbadamosi, W; Garcia, E; Nanclares, C; Famiyesin, W; et al. (Elsevier, 2016-08-26)
      Nigeria's Ebola virus disease (EVD) outbreak began when an infected diplomat from Liberia arrived Lagos, Africa's most populous city with subsequent transmission to another large city.
    • Control of Ebola virus disease outbreaks: Comparison of health care worker-targeted and community vaccination strategies.

      Robert, A; Camacho, A; Edmunds, WJ; Rosello A; Baguelin, M; Muyembe, JJT; Eggo, RM; Keita, S (Elsevier, 2019-03-02)
      Health care workers (HCW) are at risk of infection during Ebola virus disease outbreaks and therefore may be targeted for vaccination before or during outbreaks. The effect of these strategies depends on the role of HCW in transmission which is understudied. To evaluate the effect of HCW-targeted or community vaccination strategies, we used a transmission model to explore the relative contribution of HCW and the community to transmission. We calibrated the model to data from multiple Ebola outbreaks. We quantified the impact of ahead-of-time HCW-targeted strategies, and reactive HCW and community vaccination. We found that for some outbreaks (we call "type 1″) HCW amplified transmission both to other HCW and the community, and in these outbreaks prophylactic vaccination of HCW decreased outbreak size. Reactive vaccination strategies had little effect because type 1 outbreaks ended quickly. However, in outbreaks with longer time courses ("type 2 outbreaks"), reactive community vaccination decreased the number of cases, with or without prophylactic HCW-targeted vaccination. For both outbreak types, we found that ahead-of-time HCW-targeted strategies had an impact at coverage of 30%. The vaccine strategies tested had a different impact depending on the transmission dynamics and previous control measures. Although we will not know the characteristics of a new outbreak, ahead-of-time HCW-targeted vaccination can decrease the total outbreak size, even at low vaccine coverage.
    • Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries

      Loyse, Angela; Thangaraj, Harry; Easterbrook, Philippa; Ford, Nathan; Roy, Monika; Chiller, Tom; Govender, Nelesh; Harrison, Thomas S; Bicanic, Tihana; Cryptococcal Meningitis Group, Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, UK. (Elsevier, 2013-05-31)
      Cryptococcal meningitis is the leading cause of adult meningitis in sub-Saharan Africa, and contributes up to 20% of AIDS-related mortality in low-income and middle-income countries every year. Antifungal treatment for cryptococcal meningitis relies on three old, off-patent antifungal drugs: amphotericin B deoxycholate, flucytosine, and fluconazole. Widely accepted treatment guidelines recommend amphotericin B and flucytosine as first-line induction treatment for cryptococcal meningitis. However, flucytosine is unavailable in Africa and most of Asia, and safe amphotericin B administration requires patient hospitalisation and careful laboratory monitoring to identify and treat common side-effects. Therefore, fluconazole monotherapy is widely used in low-income and middle-income countries for induction therapy, but treatment is associated with significantly increased rates of mortality. We review the antifungal drugs used to treat cryptococcal meningitis with respect to clinical effectiveness and access issues specific to low-income and middle-income countries. Each drug poses unique access challenges: amphotericin B through cost, toxic effects, and insufficiently coordinated distribution; flucytosine through cost and scarcity of registration; and fluconazole through challenges in maintenance of local stocks-eg, sustainability of donations or insufficient generic supplies. We advocate ten steps that need to be taken to improve access to safe and effective antifungal therapy for cryptococcal meningitis.
    • Decentralised hepatitis C testing and treatment in rural Cambodia: evaluation of a simplified service model integrated in an existing public health system.

      Zhang, M; O'Keefe, D; Craig, J; Samley, K; Bunreth, V; Jolivet, P; Balkan, S; Marquardt, T; Dousset, JP; Le Paih, M (Elsevier, 2021-03-18)
      Background: Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement a simplified model of HCV care via decentralised health services within a rural health operational district in Battambang province, Cambodia. Methods: The study cohort included adult residents (≥18 years) of the health operational district of Moung Russei who were voluntarily screened at 13 local health centres. Serology testing was done by a rapid diagnostic test using SD Bioline HCV (SD Bioline HCV, Standard Diagnostics, South Korea) with capillary blood. HCV viral load testing was done by GeneXpert (Cepheid, Sunnyvale, CA, USA). Viraemic patients (HCV viral load ≥10 IU/mL) received pretreatment assessment by a general physician and minimal treatment evaluation tests at the health operational district referral hospital. Viraemic patients who did not have additional complications received all HCV care follow-up at the local health centres, provided by nursing staff, and patients who had decompensated cirrhosis, previously treated with a direct-acting antiviral, HBV co-infection, or other comorbidities requiring observation continued receiving care at the referral hospital with a general physician. Patients deemed eligible for treatment were prescribed oral sofosbuvir (400 mg) and daclatasvir (60 mg) once a day for 12 weeks, or 24 weeks for patients with decompensated cirrhosis or those previously treated with a direct-acting antiviral. HCV cure was defined as sustained virological response at 12 weeks after treatment (HCV viral load <10 IU/mL). Patients were assessed for serious and non-serious adverse events at any time between treatment initiation and 12 weeks post-treatment testing. Findings: Between March 12, 2018, and Jan 18, 2019, 10 425 residents (ie, 7·6% of the estimated 136 571 adults in the health operational district of Moung Russei) were screened. Of those patients screened, the median age was 44 years (IQR 31-55) and 778 (7·5%) were HCV-antibody positive. 761 (97·8%) of 778 antibody-positive patients received HCV viral load testing, and 540 (71·0%) of those tested were HCV viraemic. Among these 540 patients, linkage to treatment and follow-up care was high, with 533 (98·7%) attending a baseline consultation at the HCV clinic, of whom 530 (99·4%) initiated treatment. 485 (91·5%) of 530 patients who initiated treatment received follow-up at a health centre and 45 (8·5%) were followed up at the referral hospital. Of the 530 patients who initiated direct-acting antiviral therapy, 515 (97·2%) completed treatment. Subsequently, 466 (90·5%) of 515 patients completed follow-up, and 459 (98·5%) of 466 achieved a sustained virological response at 12 weeks after treatment. Two (0·4%) adverse events (fatigue [n=1] and stomach upset [n=1]) and five (0·9%) serious adverse events (infection [n=2], cardiovascular disease [n=1], and panic attack [n=1], with data missing for one of the causes of serious adverse events) were reported among patients who initiated treatment. All serious adverse events were deemed to be unrelated to therapy. Interpretation: This pilot project showed that a highly simplified, decentralised model of HCV care can be integrated within a rural public health system in a low-income or middle-income country, while maintaining high patient retention, treatment efficacy, and safety. The project delivered care via accessible, decentralised primary health centres, using non-specialist clinical staff, thereby enhancing the efficient use of limited resources and maximising the potential to test and treat individuals living with HCV infection.
    • Decentralized hepatitis C testing and treatment in rural Cambodia: evaluation of a simplified service model integrated in an existing public health system

      Zhang, M; O'Keefe, D; Craig, J; Samley, K; Bunreth, V; Jolivet, P; Balkan, S; Marquardt, T; Dousset, JP; Le Paih, M (Elsevier, 2021-03-18)
      Background Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement a simplified model of HCV care via decentralised health services within a rural health operational district in Battambang province, Cambodia. Methods The study cohort included adult residents (≥18 years) of the health operational district of Moung Russei who were voluntarily screened at 13 local health centres. Serology testing was done by a rapid diagnostic test using SD Bioline HCV (SD Bioline HCV, Standard Diagnostics, South Korea) with capillary blood. HCV viral load testing was done by GeneXpert (Cepheid, Sunnyvale, CA, USA). Viraemic patients (HCV viral load ≥10 IU/mL) received pretreatment assessment by a general physician and minimal treatment evaluation tests at the health operational district referral hospital. Viraemic patients who did not have additional complications received all HCV care follow-up at the local health centres, provided by nursing staff, and patients who had decompensated cirrhosis, previously treated with a direct-acting antiviral, HBV co-infection, or other comorbidities requiring observation continued receiving care at the referral hospital with a general physician. Patients deemed eligible for treatment were prescribed oral sofosbuvir (400 mg) and daclatasvir (60 mg) once a day for 12 weeks, or 24 weeks for patients with decompensated cirrhosis or those previously treated with a direct-acting antiviral. HCV cure was defined as sustained virological response at 12 weeks after treatment (HCV viral load <10 IU/mL). Patients were assessed for serious and non-serious adverse events at any time between treatment initiation and 12 weeks post-treatment testing. Findings Between March 12, 2018, and Jan 18, 2019, 10 425 residents (ie, 7·6% of the estimated 136 571 adults in the health operational district of Moung Russei) were screened. Of those patients screened, the median age was 44 years (IQR 31–55) and 778 (7·5%) were HCV-antibody positive. 761 (97·8%) of 778 antibody-positive patients received HCV viral load testing, and 540 (71·0%) of those tested were HCV viraemic. Among these 540 patients, linkage to treatment and follow-up care was high, with 533 (98·7%) attending a baseline consultation at the HCV clinic, of whom 530 (99·4%) initiated treatment. 485 (91·5%) of 530 patients who initiated treatment received follow-up at a health centre and 45 (8·5%) were followed up at the referral hospital. Of the 530 patients who initiated direct-acting antiviral therapy, 515 (97·2%) completed treatment. Subsequently, 466 (90·5%) of 515 patients completed follow-up, and 459 (98·5%) of 466 achieved a sustained virological response at 12 weeks after treatment. Two (0·4%) adverse events (fatigue [n=1] and stomach upset [n=1]) and five (0·9%) serious adverse events (infection [n=2], cardiovascular disease [n=1], and panic attack [n=1], with data missing for one of the causes of serious adverse events) were reported among patients who initiated treatment. All serious adverse events were deemed to be unrelated to therapy. Interpretation This pilot project showed that a highly simplified, decentralised model of HCV care can be integrated within a rural public health system in a low-income or middle-income country, while maintaining high patient retention, treatment efficacy, and safety. The project delivered care via accessible, decentralised primary health centres, using non-specialist clinical staff, thereby enhancing the efficient use of limited resources and maximising the potential to test and treat individuals living with HCV infection.
    • Defective Interfering Genomes and Ebola Virus Persistence

      Calain, P; Roux, L; Kolakofsky, D (Elsevier, 2016-08-13)
    • Demonstration of the Diagnostic Agreement of Capillary and Venous Blood Samples, Using Hepatitis-C Virus SD Bioline© Rapid Test: A Clinic-based Study

      Sun, C; Iwamoto, M; Calzia, A; Sreng, B; Yann, S; Pin, S; Lastrucci, C; Kimchamroeun, S; Dimanche, C; Dousset, JP; et al. (Elsevier, 2019-02)
      Simplifying hepatitis C virus (HCV) screening is a key step in achieving the elimination of HCV as a global public health threat by 2030.
    • . Deriving the optimal limit of detection for an HCV point-of-care test for viraemic infection: Analysis of a global dataset

      Freiman, JM; Wang, J; Easterbrook, PJ; Horsburgh, CR; Marinucci, F; White, LF; Kamkamidze, G; Krajden, M; Loarec, A; Njouom, R; et al. (Elsevier, 2019-07)
      Background & Aims Affordable point-of-care tests for hepatitis C (HCV) viraemia are needed to improve access to treatment in low- and middle-income countries. Our aims were to determine the target limit of detection (LOD) necessary to diagnose the majority of people with HCV eligible for treatment, and identify characteristics associated with low-level viraemia (LLV) (defined as the lowest 3% of the distribution of HCV RNA) to understand those at risk of being misdiagnosed. Methods We established a multi-country cross-sectional dataset of first available quantitative HCV RNA measurements linked to demographic and clinical data. We excluded individuals on HCV treatment. We analysed the distribution of HCV RNA and determined critical thresholds for detection of HCV viraemia. We then performed logistic regression to evaluate factors associated with LLV, and derived relative sensitivities for significant covariates. Results The dataset included 66,640 individuals with HCV viraemia from across the world. The LOD for the 95th and 99th percentiles were 3,311 IU/ml and 214 IU/ml. The LOD for the 97th percentile was 1,318 IU/ml (95% CI 1,298.4–1,322.3). Factors associated with LLV, defined as HCV RNA <1,318 IU/ml, were younger age 18–30 vs. 51–64 years (odds ratios [OR] 2.56; 95% CI 2.19–2.99), female vs. male sex (OR 1.32; 95% CI 1.18–1.49), and advanced fibrosis stage F4 vs. F0-1 (OR 1.44; 95% CI 1.21–1.69). Only the younger age group had a decreased relative sensitivity below 95%, at 93.3%. Conclusions In this global dataset, a test with an LOD of 1,318 IU/ml would identify 97% of viraemic HCV infections among almost all populations. This LOD will help guide manufacturers in the development of affordable point-of-care diagnostics to expand HCV testing and linkage to care in low- and middle-income countries. Lay summary We created and analysed a dataset from 12 countries with 66,640 participants with chronic hepatitis C virus infection. We determined that about 97% of those with viraemic infection had 1,300 IU/ml or more of circulating virus at the time of diagnosis. While current diagnostic tests can detect as little as 12 IU/ml of virus, our findings suggest that increasing the level of detection closer to 1,300 IU/ml would maintain good test accuracy and will likely enable development of more affordable portable tests for use in low- and middle-income countries.
    • Diagnostic Preparedness for Infectious Disease Outbreaks

      Perkins, M; Dye, C; Balasegaram, M; Bréchot, C; Mombouli, J; Røttingen, J; Tanner, M; Boehme, C (Elsevier, 2017-05-31)
      Diagnostics are crucial in mitigating the effect of disease outbreaks. Because diagnostic development and validation are time consuming, they should be carried out in anticipation of epidemics rather than in response to them. The diagnostic response to the 2014-15 Ebola epidemic, although ultimately effective, was slow and expensive. If a focused mechanism had existed with the technical and financial resources to drive its development ahead of the outbreak, point-of-care Ebola tests supporting a less costly and more mobile response could have been available early on in the diagnosis process. A new partnering model could drive rapid development of tests and surveillance strategies for novel pathogens that emerge in future outbreaks. We look at lessons learned from the Ebola outbreak and propose specific solutions to improve the speed of new assay development and ensure their effective deployment.
    • Ebola outbreak in Conakry, Guinea: Epidemiological, clinical, and outcome features

      Barry, M; Traoré, F A; Sako, F B; Kpamy, D O; Bah, E I; Poncin, M; Keita, S; Cisse, M; Touré, A (Elsevier, 2014-10-22)
      The authors studied the epidemiological, clinical, and outcome features of the Ebola virus disease in patients hospitalized at the Ebola treatment center (ETC) in Conakry to identify clinical factors associated with death.