This section contains articles written by MSF staff and MSF partners published in peer-reviewed journals. It contains research articles, reviews, editorials and letters. In all cases, the full text is available for free. Some articles are listed under more than one topic. The box on the right lists all the topics.

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  • Declining blood lead levels among small-scale miners participating in a safer mining pilot programme in Nigeria

    Gottesfeld, P; Meltzer, G; Costello, S; Greig, J; Thurtle, N; Bil, K; Mwangombe, BJ; Nota, MM (The BMJ, 2019-09-05)
    Objectives Our objective was to monitor blood lead levels (BLLs) of miners and ore processors participating in a pilot programme to reduce lead poisoning and take-home exposures from artisanal small-scale gold mining. A medical surveillance programme was established to assess exposures as new methods aimed at reducing lead exposures from ore were introduced in a community in Nigeria where children experienced substantial lead-related morbidity and mortality. Methods Extensive outreach and education were offered to miners, and investments were made to adopt wet methods to reduce exposures during mining and processing. We conducted medical surveillance, including a physical exam and repeated blood lead testing, for 61 miners selected from among several hundred who participated in the safer mining pilot programme and consented to testing. Venous blood lead concentrations were analysed using the LeadCare II device at approximately 3-month intervals over a period of 19 months. Results Overall geometric mean (GM) BLLs decreased by 32% from 31.6 to 21.5 µg/dL during the 19-month project. Women had a somewhat lower reduction in GM BLLs (23%) compared with men (36%). There was a statistically significant reduction in log BLLs from baseline to the final test taken by each participant (p<0.001). Conclusions The observed reductions in GM BLLs during the pilot intervention among this representative group of miners and ore processors demonstrated the effectiveness of the safer mining programme in this community. Such measures are feasible, cost-effective and can greatly improve health outcomes in mining communities.
  • Feasibility of Training Clinical Officers in Point-of-Care Ultrasound for Pediatric Respiratory Diseases in Aweil, South Sudan.

    Nadimpalli, A; Tsung, JW; Sanchez, R; Shah, S; Zelikova, E; Umphrey, L; Hurtado, N; Gonzalez, A; Teicher, C (American Society of Tropical Medicine and Hygiene, 2019-09-01)
    Lower respiratory tract infections (LRTIs) are the leading cause of deaths in children < 5 years old worldwide, particularly affecting low-resource settings such as Aweil, South Sudan. In these settings, diagnosis can be difficult because of either lack of access to radiography or clinical algorithms that overtreat children with antibiotics who only have viral LRTIs. Point-of-care ultrasound (POCUS) has been applied to LRTIs, but not by nonphysician clinicians, and with limited data from low-resource settings. Our goal was to examine the feasibility of training the mid-level provider cadre clinical officers (COs) in a Médecins Sans Frontières project in South Sudan to perform a POCUS algorithm to differentiate among causes of LRTI. Six COs underwent POCUS training, and each subsequently performed 60 lung POCUS studies on hospitalized pediatric patients < 5 years old with criteria for pneumonia. Two blinded experts, with a tiebreaker expert adjudicating discordant results, served as a reference standard to calculate test performance characteristics, assessed image quality and CO interpretation. The COs performed 360 studies. Reviewers rated 99.1% of the images acceptable and 86.0% CO interpretations appropriate. The inter-rater agreement (κ) between COs and experts for lung consolidation with air bronchograms was 0.73 (0.63-0.82) and for viral LRTI/bronchiolitis was 0.81 (0.74-0.87). It is feasible to train COs in South Sudan to use a POCUS algorithm to diagnose pneumonia and other pulmonary diseases in children < 5 years old.
  • Simplifying switch to second-line antiretroviral therapy in sub Saharan Africa: predicted effect of using a single viral load to define efavirenz-based first-line failure.

    Shroufi, A; Van Cutsem, G; Cambiano, V; Bansi-Matharu, L; Duncan, K; Murphy, RA; Maman, D; Phillips, A (Wolters Kluwer Health/Lippincott Williams & Wilkins, 2019-08-01)
    BACKGROUND: Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line ART or do so after significant delay. For people on ART with a viral load more than 1000 copies/ml, the WHO recommends a second viral load measurement 3 months after the first viral load and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated viral load more than 1000 copies/ml. Delayed second-line switch places patients at increased risk for opportunistic infections and mortality. METHODS: To assess the potential benefits of a simplified second-line ART switch strategy, we use an individual-based model of HIV transmission, progression and the effect of ART which incorporates consideration of adherence and drug resistance, to compare predicted outcomes of two policies, defining first-line regimen failure for patients on efavirenz-based ART as either two consecutive viral load values more than 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or a single viral load value more than 1000 copies/ml. We simulated a range of setting-scenarios reflecting the breadth of the sub-Saharan African HIV epidemic, taking into account potential delays in defining failure and switch to second-line ART. FINDINGS: The use of a single viral load more than 1000 copies/ml to define ART failure would lead to a higher proportion of persons with nonnucleoside reverse-transcriptase inhibitor resistance switched to second-line ART [65 vs. 48%; difference 17% (90% range 14-20%)], resulting in a median 18% reduction in the rate of AIDS-related death over setting scenarios (90% range 6-30%; from a median of 3.1 to 2.5 per 100 person-years) over 3 years. The simplified strategy also is predicted to reduce the rate of AIDS conditions by a median of 31% (90% range 8-49%) among people on first-line ART with a viral load more than 1000 copies/ml in the past 6 months. For a country of 10 million adults (and a median of 880 000 people with HIV), we estimate that this approach would lead to a median of 1322 (90% range 67-3513) AIDS deaths averted per year over 3 years. For South Africa this would represent around 10 215 deaths averted annually. INTERPRETATION: As a step towards reducing unnecessary mortality associated with delayed second-line ART switch, defining failure of first-line efavirenz-based regimens as a single viral load more than 1000 copies/ml should be considered.
  • Diabetes in humanitarian crises: the Boston Declaration.

    Kehlenbrink, S; Jaacks, M; Aebischer Perone, S; Ansbro, E; Ashbourne, E; Atkinson, C; Atkinson, M; Atun, R; Besancon, S; Boulle, P; et al. (Elsevier, 2019-08)
  • Quantifying the incidence of severe-febrile-illness hospital admissions in sub-Saharan Africa.

    Roddy, P; Dalrymple, U; Jensen, TO; Dittrich, S; Rao, VB; Pfeffer, DA; Twohig, KA; Roberts, T; Bernal, O; Guillen, E (Public Library of Science, 2019-07-25)
    Severe-febrile-illness (SFI) is a common cause of morbidity and mortality across sub-Saharan Africa (SSA). The burden of SFI in SSA is currently unknown and its estimation is fraught with challenges. This is due to a lack of diagnostic capacity for SFI in SSA, and thus a dearth of baseline data on the underlying etiology of SFI cases and scant SFI-specific causative-agent prevalence data. To highlight the public health significance of SFI in SSA, we developed a Bayesian model to quantify the incidence of SFI hospital admissions in SSA. Our estimates indicate a mean population-weighted SFI-inpatient-admission incidence rate of 18.4 (6.8-31.1, 68% CrI) per 1000 people for the year 2014, across all ages within areas of SSA with stable Plasmodium falciparum transmission. We further estimated a total of 16,200,337 (5,993,249-27,321,779, 68% CrI) SFI hospital admissions. This analysis reveals the significant burden of SFI in hospitals in SSA, but also highlights the paucity of pathogen-specific prevalence and incidence data for SFI in SSA. Future improvements in pathogen-specific diagnostics for causative agents of SFI will increase the abundance of SFI-specific prevalence and incidence data, aid future estimations of SFI burden, and enable clinicians to identify SFI-specific pathogens, administer appropriate treatment and management, and facilitate appropriate antibiotic use.
  • Hepatitis E should be considered a neglected tropical disease.

    Asman, AS; Ciglenecki, I; Wamala, JF; Lynch, J; Aggarwal, R; Rahman, M; Wong, S; Serafini, M; Moussa, AM; Dalton, HR; et al. (Public Library of Science, 2019-07-25)
  • Tuberculosis control activities in the private and public health sectors of Kenya from 2013 to 2017: how do they compare?

    Mailu, EW; Owiti, P; Ade, S; Harries, AD; Manzi, M; Omesa, E; Kiende, P; Macharia, S; Mbithi, I; Kamene, M (Oxford University Press, 2019-07-23)
    BACKGROUND: Large numbers of tuberculosis (TB) patients seek care from private for-profit providers. This study aimed to assess and compare TB control activities in the private for-profit and public sectors in Kenya between 2013 and 2017. METHODS: We conducted a retrospective cross-sectional study using routinely collected data from the National Tuberculosis, Leprosy and Lung Disease Program. RESULTS: Of 421 409 patients registered and treated between 2013 and 2017, 86 894 (21%) were from the private sector. Data collection was less complete in the private sector for nutritional assessment and follow-up sputum smear examinations (p<0.001). The private sector notified less bacteriologically confirmed TB (43.1% vs 52.6%; p<0.001) and had less malnutrition (body mass index <18.5 kg/m2; 36.4% vs 43.3%; p<0.001) than the public sector. Rates of human immunodeficiency virus (HIV) testing and antiretroviral therapy initiation were >95% and >90%, respectively, in both sectors, but more patients were HIV positive in the private sector (39.6% vs 31.6%; p<0.001). For bacteriologically confirmed pulmonary TB, cure rates were lower in the private sector, especially for HIV-negative patients (p<0.001). The private sector had an overall treatment success of 86.3% as compared with the public sector at 85.7% (p<0.001). CONCLUSIONS: The private sector is performing well in Kenya although there are programmatic challenges that need to be addressed.
  • Feasibility of engaging caregivers in at‐home surveillance of children with uncomplicated severe acute malnutrition

    Isanaka, S; Berthe, F; Nackers, F; Tang, K; Hanson, KE; Grais, RF (John Wiley & Sons, 2019-07-23)
    Many factors can contribute to low coverage of treatment for severe acute malnutrition (SAM), and a limited number of health facilities and trained personnel can constrain the number of children that receive treatment. Alternative models of care that shift the responsibility for routine clinical and anthropometric surveillance from the health facility to the household could reduce the burden of care associated with frequent facility-based visits for both healthcare providers and caregivers. To assess the feasibility of shifting clinical surveillance to caregivers in the outpatient management of SAM, we conducted a pilot study to assess caregivers' understanding and retention of key concepts related to the surveillance of clinical danger signs and anthropometric measurement over a 28-day period. At the time of a child's admission to nutritional treatment, a study nurse provided a short training to groups of caregivers on two topics: (a) clinical danger signs in children with SAM that warrant facility-based care and (b) methods to measure and monitor their child's mid-upper arm circumference. Caregiver understanding was assessed using standardized questionnaires before training, immediately after training, and 28 days after training. Knowledge of most clinical danger signs (e.g., convulsions, edema, poor appetite, respiratory distress, and lethargy) was low (0-45%) before training but increased immediately after and was retained 28 days after training. Agreement between nurse-caregiver mid-upper arm circumference colour classifications was 77% (98/128) immediately after training and 80% after 28 days. These findings lend preliminary support to pursue further study of alternative models of care that allow for greater engagement of caregivers in the clinical and anthropometric surveillance of children with SAM.
  • Decreased risk of HIV-associated TB during antiretroviral therapy expansion in rural Eswatini from 2009 to 2016: a cohort and population-based analysis

    Kerschberger, B; Schomaker, M; Telnov, A; Vambe, D; Kisyeri, N; Sikhondze, W; Pasipamire, L; Ngwenya, SM; Rusch, B; Ciglenecki, I; et al. (John Wiley & Sons, 2019-07-16)
    This paper assesses patient- and population-level trends in TB notifications during rapid expansion of antiretroviral therapy in Eswatini which has an extremely high incidence of both TB and HIV. METHODS: Patient- and population-level predictors and rates of HIV-associated TB were examined in the Shiselweni region in Eswatini from 2009 to 2016. Annual population-level denominators obtained from projected census data and prevalence estimates obtained from population-based surveys were combined with individual-level TB treatment data. Patient- and population-level predictors of HIV-associated TB were assessed with multivariate logistic and multivariate negative binomial regression models. RESULTS: Of 11 328 TB cases, 71.4% were HIV co-infected and 51.8% were women. TB notifications decreased fivefold between 2009 and 2016, from 1341 to 269 cases per 100 000 person-years. The decline was sixfold in PLHIV vs. threefold in the HIV-negative population. Main patient-level predictors of HIV-associated TB were recurrent TB treatment (adjusted odds ratio [aOR] 1.40, 95% confidence interval [CI]: 1.19-1.65), negative (aOR 1.31, 1.15-1.49) and missing (aOR 1.30, 1.11-1.53) bacteriological status and diagnosis at secondary healthcare level (aOR 1.18, 1.06-1.33). Compared with 2009, the probability of TB decreased for all years from 2011 (aOR 0.69, 0.58-0.83) to 2016 (aOR 0.54, 0.43-0.69). The most pronounced population-level predictor of TB was HIV-positive status (adjusted incidence risk ratio 19.47, 14.89-25.46). CONCLUSIONS: This high HIV-TB prevalence setting experienced a rapid decline in TB notifications, most pronounced in PLHIV. Achievements in HIV-TB programming were likely contributing factors.
  • Sickle cell disease in anaemic children in a Sierra Leonean district hospital: a case series.

    Italia, MB; Kirolos, S (Oxford University Press, 2019-07-12)
    Sickle cell disease (SCD) is the most common inherited haemoglobinopathy wordwide, with the highest prevalence in sub-Saharan Africa. Due to the lack of national strategies and scarcity of diagnostic tools in resource-limited settings, the disease may be significantly underdiagnosed. We carried out a 6-month retrospective review of paediatric admissions in a district hospital in northern Sierra Leone. Our aim was to identify patients with severe anaemia, defined as Hb < 7 g/dl, and further analyse the records of those tested for SCD. Of the 273 patients identified, only 24.5% had had an Emmel test, among which 34.3% were positive. Furthermore, only 17% of patients with a positive Emmel test were discharged on prophylactic antibiotics. Our study shows that increased awareness of SCD symptoms is required in high-burden areas without established screening programmes. In addition, the creation or strengthening of follow-up programmes for SCD patients is essential for disease control.
  • High levels of mortality, exposure to violence and psychological distress experienced by the internally displaced population of Ein Issa camp prior to and during their displacement in Northeast Syria, November 2017.

    Vernier, L; Cramond, V; Hoetjes, M; Lenglet, A; Hoare, T; Malaeb, R; Carrion Martin, AI (BioMed Central, 2019-07-11)
    BACKGROUND: War in Syria has lasted for more than eight years, causing population displacement, collapse of medical and public health services, extensive violence and countless deaths. Since November 2016, military operations in Northeast Syria intensified. In October 2017 a large influx of internally displaced persons (IDPs) arrived to Ein Issa camp, Raqqa governate. Médecins Sans Frontières (MSF) assessed the health status of recently arrived IDPs in Ein Issa camp. METHODS: MSF carried out a cross-sectional survey using simple random sampling between 8 and 18 November 2017, enrolling households who had arrived to Ein Issa camp since 1 October 2017. A questionnaire collected data on demographics, history of displacement, retrospective one-year mortality, two-week morbidities, non-communicable diseases, exposure to violence in the last year and two-week psychological distress symptoms among all household members as well as vaccination status in children aged 6 to 59 months. The latter were also screened for malnutrition. Prevalence estimates and mortality rates were calculated with their 95% confidence interval. Mortality rates were calculated as the number of deaths/10,000 persons/day using the individual person-day contribution of all household members. RESULTS: MSF surveyed 257 households (1482 participants). They reported 31 deaths in the previous year, resulting in a crude mortality rate of 0.56 deaths/10,000 persons/day (95%CI: 0.39-0.80). Conflict-related violence was the most frequently reported cause of death (64.5%). In the previous year, 31.7% (95%CI: 29.4-34.2) of the participants experienced at least one violent episode. The most frequent type of violence reported was witnessing atrocities (floggings, executions or public body displays); 18.9% (95%CI: 17.0-21.0) of the population and 9.8% (95%CI: 7.9-12.0) of the children under 15 years had witnessed such atrocities. In men over 14 years, 15.8% (95%CI: 11.9-20.8) were detained/kidnapped and 11.3% (95%CI: 8.0-15.8) tortured/beaten/attacked. In the two weeks prior to interview, 14.4% (95%CI: 10.6-19.3) of the respondents felt so hopeless that they did not want to carry on living most of the time. CONCLUSIONS: High levels of mortality, exposure to violence and psychological distress were reported. These survey results increase understanding of the impact of the conflict on the IDP population in Northeast Syria.
  • Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis.

    Dahal, P; Simpson, JA; Abdulla, S; Achan, J; Adam, I; Agarwal, A; Allan, R; Anvikar, AR; Arinaitwe, E; Ashley, EA; et al. (BioMed Central, 2019-07-05)
    BACKGROUND: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. METHODS: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model. RESULTS: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [ρ: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold. CONCLUSIONS: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
  • Malnutrition in Chakradharpur, Jharkhand: an anthropological study of perceptions and care practices from India

    Chaand, I; Horo, M; Nair, M; Harshana, A; Mahajan, R; Kashyap, V; Falero, F; Escruela, M; Burza, S; Dasgupta, R (BioMed Central, 2019-07-02)
    Background This study aims to investigate the knowledge, perception and practices related to health, nutrition, care practices, and their effect on nutrition health-seeking behaviour. Methods In order to have maximum representation, we divided Chakradharpur block in Jharkhand state into three zones (north, south and centre regions) and purposively selected 2 Ambulatory Therapeutic Feeding Centre (ATFC) clusters from each zone, along with 2 villages per ATFC (12 villages from 6 ATFCs in total). In-depth interviews and natural group discussions were conducted with mothers/caregivers, frontline health workers (FHWs), Medicins Sans Frontieres (MSF) staff, community representatives, and social leaders from selected villages. Results We found that the community demonstrates a strong dependence on traditional and cultural practices for health care and nutrition for newborns, infants and young children. Furthermore, the community relies on alternative systems of medicine for treatment of childhood illnesses such as malnutrition. The study indicated that there was limited access to and utilization of local health services by the community. Lack of adequate social safety nets, limited livelihood opportunities, inadequate child care support and care, and seasonal male migration leave mothers and caregivers vulnerable and limit proper child care and feeding practices. With respect to continuum of care, services linking care across households to facilities are fragmented. Limited knowledge of child nutrition amongst mothers and caregivers as well as fragmented service provision contribute to the limited utilization of local health services. Government FHWs and MSF field staff do not have a robust understanding of screening methods, referral pathways, and counselling. Additionally, collaboration between MSF and FHWs regarding cases treated at the ATFC is lacking, disrupting the follow up process with discharged cases in the community. Conclusions For caregivers, there is a need to focus on capacity building in the area of child nutrition and health care provision post-discharge. It is also recommended that children identified as having moderate acute malnutrition be supported to prevent them from slipping into severe acute malnutrition, even if they do not qualify for admission at ATFCs. Community education and engagement are critical components of a successful CMAM program.
  • Performance of cepheid GeneXpert HIV-1 viral load plasma assay to accurately detect treatment failure: a clinical meta-analysis

    Sacks, JA; Fong, Y; Gonzalez, MP; Andreotti, M; Baliga, S; Garrett, N; Jordan, J; Karita, E; Kulkarni, S; Mor, O; et al. (Wolters Kluwer Health / Lippincott Williams & Wilkins, 2019-07-02)
    Background: Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analysis comparing the Cepheid Xpert HIV-1 viral load plasma assay to traditional laboratory-based technologies. Methods: Cepheid Xpert HIV-1 and comparator laboratory technology plasma viral load results were provided from 13 of the 19 eligible studies, which accounted for a total of 3790 paired data points. We used random effects models to determine the accuracy and misclassification at various treatment failure thresholds (detectable, 200, 400, 500, 600, 800 and 1000 copies/ml). Results: Thirty percent of viral load test results were undetectable, while 45% were between detectable and 10 000 copies/ml and the remaining 25% were above 10 000 copies/ml. The median Xpert viral load was 119 copies/ml and the median comparator viral load was 157 copies/ml, while the log10 bias was 0.04 (0.02–0.07). The sensitivity and specificity to detect treatment failure were above 95% at all treatment failure thresholds, except for detectable, at which the sensitivity was 93.33% (95% confidence interval: 88.2–96.3) and specificity was 80.56% (95% CI: 64.6–90.4). Conclusion: The Cepheid Xpert HIV-1 viral load plasma assay results were highly comparable to laboratory-based technologies with limited bias and high sensitivity and specificity to detect treatment failure. Alternative specimen types and technologies that enable decentralized testing services can be considered to expand access to viral load.
  • Acceptability and utilization of a lipid-based nutrient supplement formulated for pregnant women in rural Niger: a multi-methods study

    Isanaka, S; Kodish, SR; Mamaty, AA; Guindo, O; Zeilani, M; Grais, RF (BioMed Central, 2019-07-01)
    Background In food insecure settings, it may be difficult for pregnant women to meet increased nutritional needs through traditional diets. A promising new strategy to fill nutrient gaps in pregnancy involves the provision of lipid-based nutrient supplements (LNS). We aimed to assess the acceptability and utilization of a 40 g LNS formulation (Epi-E) with increased micronutrient content relative to the recommended daily allowance among pregnant women in rural Niger. Methods We conducted a two-part, multi-methods study among pregnant women presenting to antenatal care in Madarounfa, Niger during two periods (Ramadan and non-Ramadan). Part 1 included two LNS test meals provided at the health center, and Part 2 included a 14-day home trial to simulate more realistic conditions outside of the health center. Open- and closed-ended questions were used to assess organoleptic properties of Epi-E using a 5-point hedonic scale after the test meals, as well as utilization and willingness to pay for Epi-E after the 14-day home trial. Results Participants consumed more than 90% of the test meal in both periods. Epi-E was rated highly in terms of overall liking, color, taste and smell during test meals in both periods (median 5/5 for all); only time, mode and frequency of consumption varied between Ramadan and non-Ramadan periods in observance of daily fasting during the holy month. Conclusion Epi- E, a 40 g LNS formulation with increased micronutrient content, was highly acceptable among pregnant women in rural Niger, and utilization was guided by household and individual considerations that varied by time period. This formulation can be further tested as a potential strategy to improve the nutritional status of pregnant women in this context.
  • . 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.
  • High prevalence of infection and low incidence of disease in child contacts of patients with drug-resistant tuberculosis: a prospective cohort study

    Huerga, H; Sanchez-Padilla, E; Melikyan, N; Atshemyan, H; Hayrapetyan, A; Ulumyan, A; Bastard, M; Khachatryan, N; Hewison, C; Varaine, F; et al. (The BMJ, 2019-07)
    Objective We aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence. Design and setting This is a prospective cohort study of paediatric contacts of adult patients with pulmonary DR-TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation, and were reassessed every 3–6 months for a period of 24 months. Children did not receive preventive treatment. Main outcome measures Prevalence and incidence of LTBI and TB disease; factors associated with prevalent LTBI. Results At initial evaluation, 3 of the 150 children included were diagnosed with TB disease (2.0%). The prevalence of LTBI was 58.7%. The incidence of LTBI was 19.9 per 100 children per year, and was especially high during the first 6 months of follow-up (33.3 per 100 children per year). No additional cases with incident disease were diagnosed during follow-up. After adjustment, prevalent LTBI was significantly associated with the child’s age, sleeping in the same house, higher household density, the index case’s age, positive smear result and presence of lung cavities. Conclusions Children in close contact with patients with DR-TB or in contact with very contagious patients had an increased risk of prevalent LTBI. Although none of the children developed TB disease during a 2-year follow-up period, screening for symptoms of TB disease, based on the prevalence of disease at recruitment, together with follow-up and repeated testing of non-infected contacts, is highly recommended in paediatric contacts of patients with DR-TB.
  • Bedaquiline overdose: A case report

    Telnov, O; Alvarez, V; Graglia, E; Molfino, L; du Cros, P; Rich, M (Elsevier, 2019-07)
    We present a case report describing outcomes in a 21 year old HIV-negative man who received treatment with bedaquiline. Due to error, dosage received comprised 4 pills of 100 mg every second day in the 60 days following the first two weeks of 4 pills of 100 mg every day. On detection, treatment was continued as per standard dosing of 200 mg given three times per week, with enhanced monitoring of ECG and liver function. The man was asymptomatic, with no signs of jaundice, abdominal pain, or abnormal heart rhythm. Toxic effects at this dosage were therefore not observed.
  • Potential use of microarray patches for vaccine delivery in low- and middle-income countries

    Peyraud, N; Zehrung, D; Jarrahian, C; Frivold, C; Orubu, T; Giersing, B (Elsevier, 2019-06-28)
    Microarray patches (MAPs), also referred to as microneedle patches, are a novel methodology that have the potential to overcome barriers to vaccine delivery in low- and middle-income countries (LMICs), and transform the way that vaccines are delivered within immunization programs. The World Health Organization’s Initiative for Vaccine Research and its partners are working to understand how MAPs could ease vaccine delivery and increase equitable access to vaccines in LMICs. Global stakeholders have been engaged to evaluate technical, economic, and programmatic challenges; to validate assumptions where possible; and to propose areas of focus to facilitate future vaccine-MAP product development. This report summarizes those learnings.
  • “Without antibiotics, I cannot treat”: A qualitative study of antibiotic use in Paschim Bardhaman district of West Bengal, India

    Nair, M; Tripathi, S; Mazumdar, S; Mahajan, R; Harshana, A; Pereira, A; Jimenez, C; Halder, D; Burza, S (Public Library of Science, 2019-06-27)
    Background Misuse of antibiotics is a well-known driver of antibiotic resistance. Given the decentralized model of the Indian health system and the shortage of allopathic doctors in rural areas, a wide variety of healthcare providers cater to the needs of patients in urban and rural settings. This qualitative study explores the drivers of antibiotic use among formal and informal healthcare providers as well as patients accessing care at primary health centers across Paschim Bardhaman district in West Bengal. Materials and methods We conducted 28 semi-structured, in-depth interviews with four groups of healthcare providers (allopathic doctors, informal health providers, nurses, and pharmacy shopkeepers) as well as patients accessing care at primary health centers and hospitals across Paschim Bardhaman district. Qualitative data was analyzed using the framework method in an inductive and deductive manner. Results Our results indicate that patients demand antibiotics from healthcare providers and seek the fastest cure possible, which influences the prescription choices of healthcare providers, particularly informal health providers. Many allopathic doctors provide antibiotics without any clinical indication due to inconsistent follow up, lack of testing facilities, risk of secondary infections, and unhygienic living conditions. Pharmaceutical company representatives actively network with informal health providers and formal healthcare providers alike, and regularly visit providers even in remote areas to market newer antibiotics. Allopathic doctors and informal health providers frequently blame the other party for being responsible for antibiotic resistance, and yet both display interdependence in referring patients to one another. Conclusions A holistic approach to curbing antibiotic resistance in West Bengal and other parts of India should focus on strengthening the capacity of the existing public health system to deliver on its promises, improving patient education and counseling, and including informal providers and pharmaceutical company representatives in community-level antibiotic stewardship efforts.

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