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 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.
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; Bygrave, H; Caballero, E; Cooper, K; Cristello, A; Digovich, K; Doocy, S; Ebrahim, S; Ewen, M; Goodman, D; Hamvas, L; Hassan, S; Hawkins, MA; Hehenkamp, A; Hunter, RF; Jenkins, D; Jobanputra, K; Kayden, S; Khan, Y; Kidy, F; Klatman, E; Lahens, L; Laing, R; Leaning, J; Le Feuvre, P; Lotchi-Yimagou, E; Luo, J; Lyons, G; McDonnell, ME; Meigs, J; Meyer, C; Miller, L; Moy, J; Mueller, K; Ogle, G; O'Laughlin, K; Park, P; Patel, P; Pfiester, E; Ratnayake, R; Reddy, A; Reed, T; Roberts, B; Robinson, P; Roy, K; Salti, N; Seiglie, J; Seita, A; Siesjo, V; Slama, S; Souris, KJ; Wispelwey, B; Yovic, S; Zaqqout, O; Zhao, M
Sickle cell disease in anaemic children in a Sierra Leonean district hospital: a case series. Italia, MB; Kirolos, S 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.
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; Awab, GR; Bassat, Q; Bjorkman, A; Bompart, F; Borrmann, S; Bousema, T; Broek, I; Bukirwa, H; Carrara, VI; Corsi, M; Cot, M; D'Alessandro, U; Davis, TME; de Wit, M; Deloron, P; Desai, M; Dimbu, PR; Djalle, D; Djimde, A; Dorsey, G; Doumbo, OK; Drakeley, CJ; Duparc, S; Edstein, MD; Espie, E; Faiz, A; Falade, C; Fanello, C; Faucher, JF; Faye, B; de Jesus Fortes, F; Gadalla, NB; Gaye, O; Gil, JP; Greenwood, B; Grivoyannis, A; Hamed, K; Hien, TT; Hughes, D; Humphreys, G; Hwang, J; Ibrahim, ML; Janssens, B; Jullien, V; Juma, E; Kamugisha, E; Karema, C; Karunajeewa, HA; Kiechel, JR; Kironde, F; Kofoed, PE; Kremsner, PG; Lameyre, V; Lee, SJ; Marsh, K; Martensson, A; Mayxay, M; Menan, H; Mens, P; Mutabingwa, TK; Ndiaye, JL; Ngasala, BE; Noedl, H; Nosten, F; Offianan, AT; Oguike, M; Ogutu, BR; Olliaro, P; Ouedraogo, JB; Piola, P; Plowe, CV; Plucinski, MM; Pratt, OJ; Premji, Z; Ramharter, M; Rogier, C; Rombo, L; Rosenthal, PJ; Sawa, P; Schramm, P; Sibley, C; Sinou, V; Sirima, S; Smithuis, F; Staedke, SG; Sutanto, I; Talisua, AO; Tarning, J; Taylor, WRJ; Temu, E; Thriemer, KL; Thuy, NN; Udhayakumar, V; Ursing, J; van Herp, M; van Vugt, M; Whitty, C; William, Y; Winnips, C; Zongo, I; Guerin, P; Price, RN; Stepniewska, K 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 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.
Bedaquiline overdose: A case report Telnov, O; Alvarez, V; Graglia, E; Molfino, L; du Cros, P; Rich, M 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.
. 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; Nguyen, KV; Shiha, G; Soliman, R; Solomon, SS; Tsertsvadze, T; Denkinger, CM; Linas, B 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; Bonnet, M 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.