Now showing items 1-20 of 2330

    • 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 (Elsevier, 2019-08)
    • 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.
    • 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; Shrestha, A; Pant, R; Peck, R; Gurley, ES (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; Boulle, A (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; 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 (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; Mosha, F; Ndlovu, Z; Plantier, JC; Saravanan, S; Scott, L; Peter, T; Doherty, M; Alexander, H; Vojnov, L (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.
    • 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.
    • Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial

      Potet, J; Smith, J; McIver, L (Public Library of Science, 2019-06-24)
      BACKGROUND: Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness. CONCLUSIONS/SIGNIFICANCE: Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms.
    • Risks and seasonal pattern for mortality among hospitalized infants in a conflict-affected area of Pakistan, 2013-2016. A retrospective chart review.

      van Deursen, B; Lenglet, A; Ariti, C; Hussain, B; Karsten, J; Roggeveen, H; Price, D; Fernhout, J; Abdi, A; Carrion Martin, AI (F1000Research, 2019-06-24)
      Background: In recent years, Médecins Sans Frontières has observed high mortality rates among hospitalized infants in Pakistan. We describe the clinical characteristics of the infants admitted between 2013 and 2016 in order to acquire a better understanding on the risk factors for mortality. Methods: We analyzed routinely collected medical data from infants (<7 months) admitted in Chaman and Dera Murad Jamali (DMJ) hospitals. The association between clinical characteristics and mortality was estimated using Poisson regression. Results: Between 2013 and 2016, 5,214 children were admitted (male/female ratio: 1.60) and 1,178 (23%) died. Days since admission was associated with a higher risk of mortality and decreased with each extra day of admission after seven days. The first 48 hours of admission was strongly associated with a higher risk of mortality. A primary diagnosis of tetanus, necrotizing enterocolitis, prematurity, sepsis and hypoxic-ischemic encephalopathy were strongly associated with higher rates of mortality. We observed an annual peak in the mortality rate in September. Conclusions: The first days of admission are critical for infant survival. Furthermore, the found male/female ratio was exceedingly higher than the national ratio of Pakistan. The observed seasonality in mortality rate by week has not been previously reported. It is fully recommended to do further in-depth research on male/female ratio differences and the reasons behind the annual peaks in mortality rate by week.
    • Tungiasis: a highly neglected disease among neglected diseases. Case series from Nduta refugee camp (Tanzania).

      Najera Villagrana, SM; Garcia Naranjo Santisteban, A (Oxford University Press, 2019-06-24)
      Tungiasis is a highly prevalent yet neglected disease of populations affected by extreme poverty. It causes great discomfort and pain, leads to social stigmatization and, when left untreated, can cause serious complications. Although natural repellents have been shown to be effective, too little is being done in terms of systematic prevention and treatment. In addition, self-treatment (usually extraction of fleas with non-sterile sharp instruments) comports high risks of infection, notably with viral hepatitis and human immunodeficiency virus. In this article, we report seven severe cases of tungiasis in children living in a refugee camp in Tanzania, all of whom were treated with surgical extraction of the fleas because the topical treatment (dimethicone) was not available. Refugee camps-particularly in sub-Saharan Africa where tungiasis is endemic-should be considered high-risk areas for the condition. Aid organizations should engage in active case searching, and health promotion should be systematically carried out.
    • Best Practices of Blood Cultures in Low- and Middle-Income Countries

      Ombelet, S; Barbe, B; Affolabi, D; Ronat, JB; Lompo, P; Lunguya, O; Jacobs, J; Hardy, L (Frontiers Media, 2019-06-18)
      Bloodstream infections (BSI) have a substantial impact on morbidity and mortality worldwide. Despite scarcity of data from many low- and middle-income countries (LMICs), there is increasing awareness of the importance of BSI in these countries. For example, it is estimated that the global mortality of non-typhoidal Salmonella bloodstream infection in children under 5 already exceeds that of malaria. Reliable and accurate diagnosis of these infections is therefore of utmost importance. Blood cultures are the reference method for diagnosis of BSI. LMICs face many challenges when implementing blood cultures, due to financial, logistical, and infrastructure-related constraints. This review aims to provide an overview of the state-of-the-art of sampling and processing of blood cultures, with emphasis on its use in LMICs. Laboratory processing of blood cultures is relatively straightforward and can be done without the need for expensive and complicated equipment. Automates for incubation and growth monitoring have become the standard in high-income countries (HICs), but they are still too expensive and not sufficiently robust for imminent implementation in most LMICs. Therefore, this review focuses on “manual” methods of blood culture, not involving automated equipment. In manual blood cultures, a bottle consisting of a broth medium supporting bacterial growth is incubated in a normal incubator and inspected daily for signs of growth. The collection of blood for blood culture is a crucial step in the process, as the sensitivity of blood cultures depends on the volume sampled; furthermore, contamination of the blood culture (accidental inoculation of environmental and skin bacteria) can be avoided by appropriate antisepsis. In this review, we give recommendations regarding appropriate blood culture sampling and processing in LMICs. We present feasible methods to detect and speed up growth and discuss some challenges in implementing blood cultures in LMICs, such as the biosafety aspects, supply chain and waste management.
    • Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi.

      Kundrick, A; Huang, Z; Carran, S; Kagoli, M; Grais, RF; Hurtado, N; Ferrari, M (BioMed Central, 2019-06-15)
      Background Despite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (RE) in the context of the 2010 measles epidemic in Malawi. Methods Using case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, RE, at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities. Results The estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated RE ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used. Conclusions Each metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.
    • Routine immediate eye examination at the point of care for diagnosis of AIDS-related Cytomegalovirus Retinitis among patients with a CD4-count < 100 in Myanmar

      Ei, WLSS; Soe, KP; Hilbig, A; Murray, J; Heiden, D (Oxford University Press, 2019-06-14)
      A retrospective review of diagnosis of cytomegalovirus retinitis (CMVR) before and after introduction of routine immediate eye examination among AIDS patient in Myanmar with an absolute CD4 T cell count <100 cells/microliter demonstrated an increased detection of CMVR from 1.1% (14/1233) to 10.7% (65/608), an improvement of approximately ten-fold. Diagnosis of CMVR was achieved a mean of 2 days after clinic enrollment.