• 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.
    • Decreased peripheral health service utilisation during an outbreak of Marburg haemorrhagic fever, Uíge, Angola, 2005.

      Roddy, P; Marchiol, A; Jeffs, B; Palma, P P; Bernal, O; de la Rosa, O; Borchert, M; Médecins Sans Frontières-Spain, Barcelona, Spain. (2008-10-04)
      In 2005, a Marburg haemorrhagic fever (MHF) outbreak occurred in Uíge province, Angola, which had its epicentre in Uíge municipality. Concurrently, a health facility located a considerable distance from the outbreak's epicentre reported a drastic reduction in attendance, possibly due to a remote effect of the ongoing MHF outbreak. Health officials should devise strategies to ensure that communities far from a filovirus haemorrhagic fever epicentre are not adversely affected by interventions at the epicentre and, to the greatest extent possible, ensure that these peripheral communities receive essential medical care during an epidemic.
    • Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut

      Carroll, M; Haldenby, S; Rickett, N; Pályi, B; Garcia-Dorival, I; Liu, X; Barker, G; Bore, J; Koundouno, F; Williamson, E; et al. (American Society for Microbiology, 2017-08-23)
      In this study, samples from the 2013-2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting. IMPORTANCE Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.
    • Defective Interfering Genomes and Ebola Virus Persistence

      Calain, P; Roux, L; Kolakofsky, D (Elsevier, 2016-08-13)
    • Defining priority medical devices for cancer management: a WHO initiative

      Velazquez Berumen, A; Jimenez Moyao, G; Rodriguez, NM; Ilbawi, AM; Migliore, A; Shulman, LN (The Lancet, 2018-12)
    • 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.
    • Dengue in Western Uganda: a prospective cohort of children presenting with undifferentiated febrile illness

      Boyce, RM; Collins, M; Muhindo, R; Nakakande, R; Ciccone, EJ; Grounds, S; Espinoza, D; Zhu, Y; Matte, M; Ntaro, M; et al. (BMC, 2020-11-11)
      Background The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. Methods Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. Results Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). Conclusions Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.
    • . 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.
    • Describing readmissions to an Ebola case management centre (CMC), Sierra Leone, 2014

      Fitzpatrick, G; Vogt, F; Moi Gbabai, Ob; Black, B; Santantonio, M; Folkesson, E; Decroo, T; Van Herp, M (European Centre for Disease Prevention and Control, 2014-10-09)
    • Description of a large measles epidemic in Democratic Republic of Congo, 2010-2013

      Mancini, Silvia; Coldiron, Matthew E; Ronsse, Axelle; Ilunga, Benoît Kebela; Porten, Klaudia; Grais, RFebecca F (BioMed Central, 2014-07-03)
      Although measles mortality has declined dramatically in Sub-Saharan Africa, measles remains a major public health problem in countries like the Democratic Republic of Congo (DRC). Here, we describe the large measles epidemic that occurred in the Democratic Republic of Congo between 2010 and 2013 using data from the national surveillance system as well as vaccine coverage surveys to provide a snapshot of the epidemiology of measles in DRC.
    • Descriptive Epidemiology of Typhoid Fever during an Epidemic in Harare, Zimbabwe, 2012

      Polonsky, Jonathan A; Martínez-Pino, Isabel; Nackers, Fabienne; Chonzi, Prosper; Manangazira, Portia; Van Herp, Michel; Maes, Peter; Porten, Klaudia; Luquero, Francisco J (Public Library of Science, 2014-12-08)
      Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare.
    • Descriptive spatial analysis of the cholera epidemic 2008-2009 in Harare, Zimbabwe: a secondary data analysis.

      Luque Fernández, Miguel Ángel; Mason, Peter R; Gray, Henry; Bauernfeind, Ariane; Fesselet, Jean François; Maes, Peter; Médecins Sans Frontières, Medical department (Brussels Operational Center), 94, rue Dupre, 1090 Brussels, Belgium. (2011-01)
      This ecological study describes the cholera epidemic in Harare during 2008-2009 and identifies patterns that may explain transmission. Rates ratios of cholera cases by suburb were calculated by a univariate regression Poisson model and then, through an Empirical Bayes modelling, smoothed rate ratios were estimated and represented geographically. Mbare and southwest suburbs of Harare presented higher rate ratios. Suburbs attack rates ranged from 1.2 (95% Cl = 0.7-1.6) cases per 1000 people in Tynwald to 90.3 (95% Cl = 82.8-98.2) in Hopley. The identification of this spatial pattern in the spread, characterised by low risk in low density residential housing, and a higher risk in high density south west suburbs and Mbare, could be used to advocate for improving water and sanitation conditions and specific preparedness measures in the most affected areas.
    • The Development of a Multilingual Tool for Facilitating the Primary-Specialty Care Interface in Low Resource Settings: the MSF Tele-Expertise System

      Bonnardot, Laurent; Liu, Joanne; Wootton, Elizabeth; Amoros, Isabel; Olson, David; Wong, Sidney; Wootton, Richard (Frontiers Media, 2014-08-26)
    • Development of a Prediction Model for Ebola Virus Disease: A Retrospective Study in Nzérékoré Ebola Treatment Center, Guinea

      Loubet, P; Palich, R; Kojan, R; Peyrouset, O; Danel, C; Nicholas, S; Conde, M; Porten, K; Augier, A; Yazdanpanah, Y (American Society of Tropical Medicine and Hygiene, 2016-12-07)
      The 2014 Ebola epidemic has shown the importance of accurate and rapid triage tools for patients with suspected Ebola virus disease (EVD). Our objective was to create a predictive score for EVD. We retrospectively reviewed all suspected cases admitted to the Ebola treatment center (ETC) in Nzérékoré, Guinea, between December 2, 2014, and February 23, 2015. We used a multivariate logistic regression model to identify clinical and epidemiological factors associated with EVD, which were used to create a predictive score. A bootstrap sampling method was applied to our sample to determine characteristics of the score to discriminate EVD. Among the 145 patients included in the study (48% male, median age 29 years), EVD was confirmed in 76 (52%) patients. One hundred and eleven (77%) patients had at least one epidemiological risk factor. Optimal cutoff value of fever to discriminate EVD was 38.5°C. After adjustment on presence of a risk factor, temperature higher than 38.5°C (odds ratio [OR] = 18.1, 95% confidence interval [CI] = 7.6-42.9), and anorexia (OR = 2.5, 95% CI = 1.1-6.1) were independently associated with EVD. The score had an area under curve of 0.85 (95% CI = 0.78-0.91) for the prediction of laboratory-confirmed EVD. Classification of patients in a high-risk group according to the score had a lower sensitivity (71% versus 86%) but higher specificity (85% versus 41%) than the existing World Health Organization algorithm. This score, which requires external validation, may be used in high-prevalence settings to identify different levels of risk in EVD suspected patients and thus allow a better orientation in different wards of ETC.
    • Development of Diagnostics for Chagas Disease: Where Should We Put Our Limited Resources?

      Picado, A; Angheben, A; Marchiol, A; Alarcón de Noya, B; Flevaud, L; Pinazo, MJ; Gállego, M; Meymandi, S; Moriana, S (Public Library of Science, 2017-01-05)
    • Diagnosis and Management of Ebola Samples in the Laboratory

      de La Vega, MA; Bello, A; Chaillet, P; Kobinger, GP (Taylor & Francis - We regret that this article is behind a paywall., 2016-05-13)
      The magnitude of the 2014–2016 West African Ebola virus outbreak has highlighted the importance of immediate and rapid deployment of control measures in affected areas. While many prophylactic and therapeutic options entered clinical trials in the past two years, larger use to impact on Ebola spread will not be possible until at least one product meets final approval by regulatory agencies. Control of the West African outbreak was achieved almost entirely by breaking chain of transmissions through case identification and specialized treatment, communication, safe burials and other proven methods. To achieve this in a timely manner, epidemiologists and medical teams are working in concert with laboratories to identify infected individuals and provide care within Ebola treatment units. Herein, we review an outbreak response workflow from the point of view of mobile laboratories and summarize methods that have been used by them during the West African Ebola virus outbreak of 2014–2016.
    • Diagnostic accuracy of VIKIA® Rota-Adeno and Premier™ Rotaclone® tests for the detection of Rotavirus in Niger

      Lagare, A; Moumouni, A; Kaplon, J; Langendorf, C; Pothier, P; Grais, RF; Issaka, B; Page, A (BioMed Central, 2017-10-23)
      We conducted a parallel evaluation of the diagnostic accuracy of VIKIA® Rota-Adeno, a rapid diagnostic test (RDT) and Premier™ Rotaclone® an enzyme immunoassay (EIA) using reverse transcription polymerase chain reaction (RT-PCR) as the reference standard. The study was part of a rotavirus surveillance project in Niger.
    • 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.
    • Diagnostics for filovirus detection: impact of recent outbreaks on the diagnostic landscape

      Emperador DM; Mazzola LT; Trainor BW; Chua A; Kelly-Cirino C (BMJ Publishing Group, 2019-02-07)
      Ebolaviruses and Marburg virus (MARV) both belong to the family Filoviridae and cause severe haemorrhagic fever in humans. Due to high mortality rates and potential for spread from rural to urban regions, they are listed on the WHO R&D blueprint of high-priority pathogens. Recent ebolavirus outbreaks in Western and Central Africa have highlighted the importance of diagnostic testing in epidemic preparedness for these pathogens and led to the rapid development of a number of commercially available benchtop and point-of-care nucleic acid amplification tests as well as serological assays and rapid diagnostic tests. Despite these advancements, challenges still remain. While products approved under emergency use licenses during outbreak periods may continue to be used post-outbreak, a lack of clarity and incentive surrounding the regulatory approval pathway during non-outbreak periods has deterred many manufacturers from seeking full approvals. Waning of funding and poor access to samples after the 2014–2016 outbreak also contributed to cessation of development once the outbreak was declared over. There is a need for tests with improved sensitivity and specificity, and assays that can use alternative sample types could reduce the need for invasive procedures and expensive equipment, making testing in field conditions more feasible. For MARV, availability of diagnostic tests is still limited, restricted to a single ELISA test and assay panels designed to differentiate between multiple pathogens. It may be helpful to extend the target product profile for ebolavirus diagnostics to include MARV, as the viruses have many overlapping characteristics.