Now showing items 21-40 of 2795

    • Suicidal ideation and attempt among school going adolescents in Bhutan – a secondary analysis of a global school-based student health survey in Bhutan 2016

      Dema, T; Thinley, S; Lhazeen, K; Penjore, T; Tenzin, K; Subba, D; Rani, M; Tripathy, J; Dhendup, T; Gurung, M; et al. (Springer Science and Business Media LLC, 2019-12-02)
      Suicide is one of the leading causes of death and Disability Adjusted Life Years (DALYs) worldwide. The economic, emotional and human cost of suicidal behaviour to individuals, families, communities and society makes it a serious public health issue. We aim to determine the prevalence and factors associated with self-reported suicidal behaviour (suicidal ideation and attempt) among school going adolescents (13–17 years).
    • A review of the WHO malaria rapid diagnostic test product testing programme (2008–2018): performance, procurement and policy

      Cunningham, J; Jones, S; Gatton, M; Barnwell, J; Cheng, Q; Chiodini, P; Glenn, J; Gonzalez, I; Kosack, C; Nhem, S; et al. (Springer Science and Business Media LLC, 2019-12-02)
      Malaria rapid diagnostic tests (RDTs) emerged in the early 1990s into largely unregulated markets, and uncertain field performance was a major concern for the acceptance of tests for malaria case management. This, combined with the need to guide procurement decisions of UN agencies and WHO Member States, led to the creation of an independent, internationally coordinated RDT evaluation programme aiming to provide comparative performance data of commercially available RDTs. Products were assessed against Plasmodium falciparum and Plasmodium vivax samples diluted to two densities, along with malaria-negative samples from healthy individuals, and from people with immunological abnormalities or non-malarial infections. Three measures were established as indicators of performance, (i) panel detection score (PDS) determined against low density panels prepared from P. falciparum and P. vivax wild-type samples, (ii) false positive rate, and (iii) invalid rate, and minimum criteria defined. Over eight rounds of the programme, 332 products were tested. Between Rounds 1 and 8, substantial improvements were seen in all performance measures. The number of products meeting all criteria increased from 26.8% (11/41) in Round 1, to 79.4% (27/34) in Round 8. While products submitted to further evaluation rounds under compulsory re-testing did not show improvement, those voluntarily resubmitted showed significant increases in P. falciparum (p = 0.002) and P. vivax PDS (p < 0.001), with more products meeting the criteria upon re-testing. Through this programme, the differentiation of products based on comparative performance, combined with policy changes has been influential in the acceptance of malaria RDTs as a case-management tool, enabling a policy of parasite-based diagnosis prior to treatment. Publication of product testing results has produced a transparent market allowing users and procurers to clearly identify appropriate products for their situation, and could form a model for introduction of other, broad-scale diagnostics.
    • Ensuring On-site Ebola Patient Monitoring and Follow-up: Development of a Laboratory Structure Embedded in an Ebola Treatment Center.

      Williams, A; Amand, M; Van den Bergh, R; De Clerck, H; Antierens, A; Chaillet, P (Cambridge University Press, 2019-12-01)
      The capacity to rapidly distinguish Ebola virus disease from other infectious diseases and to monitor biochemistry and viremia levels is crucial to the clinical management of suspected Ebola virus disease cases. This article describes the design and practical considerations of a laboratory straddling the high- and low-risk zones of an Ebola treatment center to produce timely diagnostic and clinical results for informed case management of Ebola virus disease in real-life conditions. This innovation may be of relevance for actors requiring flexible laboratory implementation in contexts of high-communicability, high-lethality disease outbreaks.
    • Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression

      Musinguzi, N; Castillo-Mancilla, J; Morrow, M; Byakwaga, H; Mawhinney, S; Burdo, TH; Boum, Y; Muzoora, C; Bwana, BM; Siedner, MJ; et al. (Lippincott, Williams & Wilkins, 2019-12-01)
      Background: Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. Setting: We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. Methods: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8+ T-cell activation (HLA-DR+/CD38+ coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. Results: Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR+/CD8+ (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. Conclusions: Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.
    • What can be learnt from Ebola about the dangers of the global health security approach?

      Roper, S (Transactions of the Royal Society, 2019-12-01)
      The current outbreak of Ebola that has been raging out of control for over 1 y in the Democratic Republic of Congo (DRC) has brought back painful memories from West Africa about the dangers of the global health security approach. Drawing on the author’s personal experience of working as a medic in both outbreaks, this article reflects on the challenges of responding to the disease inside a global health security framework. Insights and recommendations are made as to how the global health community can contribute towards gaining better control of Ebola both now and in the future.
    • A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups

      Dodd, L; Follman, D; Proschan, M; Wang, J; Malvy, D; Horby, P; Gouel-Cheron, A; Ciglenecki, I; Davey, R; Lane, C; et al. (American Association for the Advancement of Science, 2019-11-27)
      Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013-2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.
    • Refused and referred-persistent stigma and discrimination against people living with HIV/AIDS in Bihar: a qualitative study from India

      Nair, M; Kumar, P; Harshana, A; Kazmi, S; Pandey, S; Burza, S; Moreto-Planas, L (British Medical Journal BMJ, 2019-11-25)
      OBJECTIVES: This study aimed to explore barriers to accessing care, if any, among people living with HIV/AIDS (PLHA) in two districts of Bihar. We also aimed to assess attitudes towards PLHA among healthcare providers and community members. DESIGN: This qualitative study used an exploratory study design through thematic analysis of semistructured, in-depth interviews. SETTING: Two districts were purposively selected for the study, namely the capital Patna and a peripheral district located approximately 100 km from Patna, in order to glean insights from a diverse sample of respondents. PARTICIPANTS: Our team purposively selected 71 participants, including 35 PLHA, 10 community members and 26 healthcare providers. RESULTS: The overarching theme that evolved from these data through thematic coding identified that enacted stigma and discrimination interfere with each step in the HIV care continuum for PLHA in Bihar, India, especially outside urban areas. The five themes that contributed to these results include: perception of HIV as a dirty illness at the community level; non-consensual disclosure of HIV status; reliance on identifying PLHA to guide procedures and resistance to universal precautions; refusal to treat identified PLHA and referrals to other health centres for treatment; and inadequate knowledge and fear among health providers with respect to HIV transmission. CONCLUSIONS: The continued presence of discriminatory and stigmatising attitudes towards PLHA negatively impacts both disclosure of HIV status as well as access to care and treatment. We recognise a pressing need to improve the knowledge of HIV transmission, and implement universal precautions across all health facilities in the state, not just to reduce stigma and discrimination but also to ensure proper infection control. In order to improve treatment adherence and encourage optimal utilisation of services, it is imperative that the health system invest more in stigma reduction in Bihar and move beyond more ineffective, punitive approaches.
    • Management of diabetes and associated costs in a complex humanitarian setting in the Democratic Republic of Congo: a retrospective cohort study

      Ansbro, EM; Roberts, B; Jobanputra, K; Biringanine, M; Caleo, G; Prieto-Merino, D; Sadique, Z; Perel, P (BMJ, 2019-11-24)
      Objective We aimed to evaluate an Integrated Diabetic Clinic within a Hospital Outpatient Department (IDC-OPD) in a complex humanitarian setting in North Kivu, Democratic Republic of Congo. Specific objectives were to: (1) analyse diabetes intermediate clinical and programmatic outcomes (blood pressure (BP)/glycaemic control, visit volume and frequency); (2) explore the association of key insecurity and related programmatic events with these outcomes; and (3) describe incremental IDC-OPD programme costs. Design Retrospective cohort analysis of routine programmatic data collected from January 2014 to February 2017; analysis of programme costs for 2014/2015. Setting Outpatient diabetes programme in Mweso hospital, supported by Médecins sans Frontières, in North Kivu, Demographic Republic of Congo. Participants Diabetes patients attending IDC-OPD. Outcome measures Intermediate clinical and programmatic outcome trends (BP/ glycaemic control; visit volume/frequency); incremental programme costs. Results Of 243 diabetes patients, 44.6% were women, median age was 45 (IQR 32–56); 51.4% were classified type 2. On introduction of IDC-OPD, glucose control improved and patient volume and visit interval increased. During insecurity, control rates were initially maintained by a nurse-provided, scaled-back service, while patient volume and visit interval decreased. Following service suspension due to drug stock-outs, patients were less likely to achieve control, improving on service resumption. Total costs decreased 16% from 2014 (€36 573) to 2015 (€30 861). Annual cost per patient dropped from €475 in 2014 to €214 in 2015 due to reduced supply costs and increased patient numbers. Conclusions In a chronic conflict setting, we documented that control of diabetes intermediate outcomes was achievable during stable periods. During insecure periods, a simplified, nurse-led model maintained control rates until drug stock-outs occurred. Incremental per patient annual costs were lower than chronic HIV care costs in low-income settings. Future operational research should define a simplified diabetes care package including emergency preparedness.
    • Genotyping and outcomes of presumptive second line ART failure cases switched to third line or maintained on second line ART in Mumbai, India

      Gill, N; Van den Bergh, R; Wut Yee Kyaw, K; Laxmeshwar, C; Das, M; Rastogi, S; Mansoor, H; Kalon, S; Isaakidis, P; Arago Galindo, M (2019-11-21)
      BACKGROUND: HIV programs are increasingly confronted with failing antiretroviral therapy (ART), including second-line regimens. WHO has provided guidelines on switching to third-line ART. In a Médecins Sans Frontières clinic in Mumbai, India, receiving referred presumptive second-line ART failure cases, an evidence-based protocol consisting of viral load (VL) testing, enhanced adherence counselling (EAC) and genotype for switching was implemented. OBJECTIVE: To document the outcome and genotype of presumptive second-line ART failure cases switched to third-line or maintained on second-line ART. DESIGN: Retrospective cohort study of patients referred between January 2011 and September 2017. RESULTS: The cases (n = 120) were complex with median 9.2 years of ART exposure, poor adherence at baseline, and exposure to multiple ART regimens other than recommended by WHO. Out of 90 evaluated cases, 39(43%) were maintained on second-line ART. Forty-nine (54%) were ever switched to third-line ART. Twelve months virological suppression was 72% in the second-line and 93% in the third-line ART cohort, while retention in care was 80% and 94% respectively. Genotyping showed 62% resistance for PIs, and 52% triple class resistance to NRTIs, NNRTIs and PIs. Resistance was noted for the new class of integrase inhibitors, and for different drugs without any documented previous exposure to the same drug. CONCLUSION: Adopting WHO guidelines on switching ART regimens and provision of EAC can prevent unnecessary switching/exposure to third-line ART regimens. Genotyping is urgently required in national HIV programs, which currently use only the exposure history of patients for switching to third-line ART regimens.
    • Mortality and health survey, Walikale, Democratic Republic of the Congo, 2017: an example of the use of survey data for humanitarian program planning

      Robinson, E; Crispino, V; Ouabo, A; Soung Iballa, F; Kremer, R; Serbassi, M; van Lenthe, M; Carrion Martin, A (Springer Science and Business Media LLC, 2019-11-21)
      Background: During humanitarian crises, health information systems are often lacking and surveys are a valuable tool to assess the health needs of affected populations. In 2013, a mortality and health survey undertaken by Médecins Sans Frontières (MSF) in the conflict affected Walikale territory of North Kivu, Democratic Republic of the Congo (DRC), indicated mortality rates exceeding humanitarian crisis thresholds and a high burden of mortality and morbidity due to malaria. In late 2017, after a period of relative stability, MSF reassessed the health status of the population through a second survey to guide ongoing operations. Methods: A two-stage cluster survey, selecting villages using probability proportional to size and households using random walk procedures, was conducted. Household members were interviewed on morbidity and mortality, healthcare use, vaccination status, and bednet availability. Results: The sample included 5711 persons in 794 households. The crude mortality rate (CMR) and under-five mortality rate (U5MR) were 0.98 per 10,000 persons/day (95% confidence interval (CI) 0.78–1.2) and 1.3 per 10,000 persons/day (95% CI): 0.82–2.0), respectively. The most frequently reported causes of death were fever/malaria (31%), diarrhoea (15%) and respiratory infections (8%). In 89% of households at least one person was reported as falling ill in the previous 2 weeks, and 58% sought healthcare. Cost was the main barrier amongst 58% of those who did not seek healthcare. Coverage of measles-containing-vaccine was 62% in under-fives. Sufficient bednet coverage (1 bednet/2 people) was reported from 17% of households. Conclusion: The second survey illustrates that although mortality is now just below crisis thresholds, the area still experiences excess mortality and has substantial health needs. The study results have supported the further expansion of integrated community case management to improve access to care for malaria, diarrhoea and respiratory infections. Such surveys are important to orient operations to the health needs of the population being served and also highlight the ongoing vulnerability of populations after humanitarian crises.
    • Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda

      Grais, R; Warimwe, G; Kimathi, D; Juan, A; Bejon, P; epicentre (F1000 Research Ltd, 2019-11-20)
      Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa. Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days – up to 2 years – post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose. Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops.
    • What drives mortality among HIV patients in a conflict setting? A prospective cohort study in the Central African Republic

      Crellen, T; Ssonko, C; Piening, T; Simaleko, MM; Geiger, K; Siddiqui, MR (2019-11-14)
      BACKGROUND: Provision of antiretroviral therapy (ART) during conflict settings is rarely attempted and little is known about the expected patterns of mortality. The Central African Republic (CAR) continues to have a low coverage of ART despite an estimated 110,000 people living with HIV and 5000 AIDS-related deaths in 2018. We present results from a cohort in Zemio, Haut-Mboumou prefecture. This region had the highest prevalence of HIV nationally (14.8% in a 2010 survey), and was subject to repeated attacks by armed groups on civilians during the observed period. METHODS: Conflict from armed groups can impact cohort mortality rates i) directly if HIV patients are victims of armed conflict, or ii) indirectly if population displacement or fear of movement reduces access to ART. Using monthly counts of civilian deaths, injuries and abductions, we estimated the impact of the conflict on patient mortality. We also determined patient-level risk factors for mortality and how the risk of mortality varies with time spent in the cohort. Model-fitting was performed in a Bayesian framework, using logistic regression with terms accounting for temporal autocorrelation. RESULTS: Patients were recruited and observed in the HIV treatment program from October 2011 to May 2017. Overall 1631 patients were enrolled and 1628 were included in the analysis giving 48,430 person-months at risk and 145 deaths. The crude mortality rate after 12 months was 0.92 (95% CI 0.90, 0.93). Our model showed that patient mortality did not increase during periods of heightened conflict; the odds ratios (OR) 95% credible interval (CrI) for i) civilian fatalities and injuries, and ii) civilian abductions on patient mortality both spanned unity. The risk of mortality for individual patients was highest in the second month after entering the cohort, and declined seven-fold over the first 12 months. Male sex was associated with a higher mortality (odds ratio 1.70 [95% CrI 1.20, 2.33]) along with the severity of opportunistic infections (OIs) at baseline (OR 2.52; 95% CrI 2.01, 3.23 for stage 2 OIs compared with stage 1). CONCLUSIONS: Our results show that chronic conflict did not appear to adversely affect rates of mortality in this cohort, and that mortality was driven predominantly by patient-specific risk factors. The risk of mortality and recovery of CD4 T-cell counts observed in this conflict setting are comparable to those in stable resource poor settings, suggesting that conflict should not be a barrier in access to ART.
    • A Consensus Framework for the Humanitarian Surgical Response to Armed Conflict in 21st Century Warfare

      Wren, S; Wild, H; Gurney, J; Amirtharajah, M; Osmers, I; Pagano, H; Trelles, M; Brown, ZW; Burckle, FM (2019-11-13)
      Importance: Armed conflict in the 21st century poses new challenges to a humanitarian surgical response, including changing security requirements, access to patients, and communities in need, limited deployable surgical assets, resource constraints, and the requirement to address both traumatic injuries as well as emergency surgical needs of the population. At the same time, recent improvements in trauma care and systems have reduced injury-related mortality. This combination of new challenges and medical capabilities warrants reconsideration of long-standing humanitarian surgery protocols. Objective: To describe a consensus framework for surgical care designed to respond to this emerging need. Design, Setting, and Participants: An international group of 35 representatives from humanitarian agencies, US military, and academic trauma programs was invited to the Stanford Humanitarian Surgical Response in Conflict Working Group to engage in a structured process to review extant trauma protocols and make recommendations for revision. Main Outcomes and Measures: The working group's method adapted core elements of a modified Delphi process combined with consensus development conference from August 3 to August 5, 2018. Results: Lessons from civilian and military trauma systems as well as recent battlefield experiences in humanitarian settings were integrated into a tiered continuum of response from point of injury through rehabilitation. The framework addresses the security and medical requirements as well as ethical and legal principles that guide humanitarian action. The consensus framework includes trained, lay first responders; far-forward resuscitation/stabilization centers; rapid damage control surgical access; and definitive care facilities. The system also includes nontrauma surgical care, injury prevention, quality improvement, data collection, and predeployment training requirements. Conclusions and Relevance: Evidence suggests that modern trauma systems save lives. However, the requirements of providing this standard of care in insecure conflict settings places new burdens on humanitarian systems that must provide both emergency and trauma surgical care. This consensus framework integrates advances in trauma care and surgical systems in response to a changing security environment. It is possible to reduce disparities and improve the standard of care in these settings.
    • Prevalence and correlates of low serum calcium in late pregnancy: A cross sectional study in the Nkongsamba Regional Hospital; Littoral Region of Cameroon

      Ajong, AB; Kenfack, B; Ali, IM; Yakum, MN; Telefo, PB (Public Library of Science, 2019-11-07)
      Introduction Women from low and middle income countries are generally more likely to have sub-optimal calcium intake. The objective of this study was to assess serum calcium disorders and correlates in late pregnancy. Methods We conducted from December 2018 to April 2019, a cross-sectional hospital-based study targeting pregnant women in late pregnancy in the Nkongsamba Regional Hospital. Data were collected by measurement of parameters (weight, height, blood pressure and foetal birthweight), administration of a semi-structured questionnaire and analysis of blood samples collected from each participant. Absorption spectrophotometry was used to measure serum calcium and albumin concentrations and corrected serum calcium calculated from the Payne’s equation. With a statistical significant threshold set at p-value = 0.05, the odds ratio was used as a measure of the strength of association between hypocalcaemia and maternofoetal variables. Results We enrolled a total of 354 consenting participants with a mean age of 27.41±5.84 years. The prevalence of hypocalcaemia in late pregnancy was 58.76 [53.42–63.90]%. The rate of calcium supplementation in pregnancy was 57.63[52.28–62.80]% with a mean duration of supplementation of 3.69±1.47 months. When controlled for marital status, age, level of education, and gestational age at delivery, pregnant women with systolic blood pressures below 130 mmHg were significantly less likely to have hypocalcaemia than their counterparts with higher systolic blood pressures (Adjusted Odds Ratio = 0.41[0.18–0.89], p-value = 0.020). No statistically significant associations were found between diastolic blood pressure, body mass index, foetal birth weight and hypocalcaemia. Conclusion Hypocalcaemia in late pregnancy is highly prevalent (59%) among women accessing reproductive services at the Nkongsamba Regional Hospital. There is also a wide gap in calcium supplementation compared to World Health Organization recommendations. Hypocalcaemia is significantly associated to higher systolic blood pressure in pregnancy. Systematic calcium supplementation and consumption of high calcium containing locally available meals should be encouraged.
    • Diagnostic sensitivity of SILVAMP TB-LAM (FujiLAM) point-of-care urine assay for extra-pulmonary tuberculosis in people living with HIV

      Kerkhoff, AD; Sossen, B; Schutz, C; Reipold, EI; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Nicol, MP; et al. (European Respiratory Society, 2019-11-07)
    • Maternal health after Ebola: unmet needs and barriers to healthcare in rural Sierra Leone

      Elston, JWT; Danis, K; Gray, N; West, K; Lokuge, K; Black, B; Stringer, B; Jimmisa, AS; Biankoe, A; Sanko, MO; et al. (Oxford University Press, 2019-11-07)
      Sierra Leone has the world’s highest estimated maternal mortality. Following the 2014–16 Ebola outbreak, we described health outcomes and health-seeking behaviour amongst pregnant women to inform health policy. In October 2016–January 2017, we conducted a sequential mixed-methods study in urban and rural areas of Tonkolili District comprising: household survey targeting women who had given birth since onset of the Ebola outbreak; structured interviews at rural sites investigating maternal deaths and reporting; and in-depth interviews (IDIs) targeting mothers, community leaders and health workers. We selected 30 clusters in each area: by random GPS points (urban) and by random village selection stratified by population size (rural). We collected data on health-seeking behaviours, barriers to healthcare, childbirth and outcomes using structured questionnaires. IDIs exploring topics identified through the survey were conducted with a purposive sample and analysed thematically. We surveyed 608 women and conducted 29 structured and 72 IDIs. Barriers, including costs of healthcare and physical inaccessibility of healthcare facilities, delayed or prevented 90% [95% confidence interval (CI): 80–95] (rural) vs 59% (95% CI: 48–68) (urban) pregnant women from receiving healthcare. Despite a general preference for biomedical care, 48% of rural and 31% of urban women gave birth outside of a health facility; of those, just 4% and 34%, respectively received skilled assistance. Women expressed mistrust of healthcare workers (HCWs) primarily due to payment demanded for ‘free’ healthcare. HCWs described lack of pay and poor conditions precluding provision of quality care. Twenty percent of women reported labour complications. Twenty-eight percent of villages had materials to record maternal deaths. Pregnant women faced important barriers to care, particularly in rural areas, leading to high preventable mortality and morbidity. Women wanted to access healthcare, but services available were often costly, unreachable and poor quality. We recommend urgent interventions, including health promotion, free healthcare access and strengthening rural services to address barriers to maternal healthcare.
    • Distribution of advanced HIV disease from three high HIV prevalence settings in Sub-Saharan Africa: a secondary analysis data from three population-based cross-sectional surveys in Eshowe (South Africa), Ndhiwa (Kenya) and Chiradzulu (Malawi)

      Chihana, ML; Huerga, H; Van Cutsem, G; Ellman, T; Goemaere, E; Waniala, S; Masiku, C; Szumilin, E; Etard, JF; Maman, D; et al. (Taylor & Francis, 2019-11-04)
      Background: Despite substantial progress in antiretroviral therapy (ART) scale up, some people living with HIV (PLHIV) continue to present with advanced HIV disease, contributing to ongoing HIV-related morbidity and mortality. Objective: We aimed to quantify population-level estimates of advanced HIV from three high HIV prevalence settings in Sub-Saharan Africa. Methods: Three cross-sectional surveys were conducted in (Ndhiwa (Kenya): September–November 2012), (Chiradzulu (Malawi): February–May 2013) and (Eshowe (South Africa): July–October 2013). Eligible individuals 15–59 years old who consented were interviewed at home followed by rapid HIV test and CD4 count test if tested HIV-positive. Advanced HIV was defined as CD4 < 200 cells/µl. We used logistic regression to identify patient characteristics associated with advanced HIV. Results: Among 18,991 (39.2% male) individuals, 4113 (21.7%) tested HIV-positive; 385/3957 (9.7% (95% Confidence Interval [CI]: 8.8–10.7)) had advanced HIV, ranging from 7.8% (95%CI 6.4–9.5) Chiradzulu (Malawi) to 11.8% (95%CI 9.8–14.2) Ndhiwa (Kenya). The proportion of PLHIV with advanced disease was higher among men 15.3% (95% CI 13.2–17.5) than women 7.5% (95%CI 6.6–8.6) p < 0.001. Overall, 62.7% of all individuals with advanced HIV were aware of their HIV status and 40.3% were currently on ART. Overall, 65.6% of individuals not on ART had not previously been diagnosed with HIV, while only 29.6% of those on ART had been on ART for ≥6 months. Individuals with advanced HIV disease were more likely to be men (adjusted Odds Ratio [aOR]; 2.1 (95%CI 1.7–2.6), and more likely not to be on ART (aOR; 1.7 (95%CI 1.3–2.1). Conclusion: In our study, about 1 in 10 PLHIV had advanced HIV with nearly 40% of them unaware of their HIV status. However, a substantial proportion of patients with advanced HIV were established on ART. Our findings suggest the need for a dual focus on alternative testing strategies to identify PLHIV earlier as well as improving ART retention.
    • Culture conversion at six months in patients receiving delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis.

      Seung, KJ; Khan, P; Franke, MF; Ahmed, S; Aiylchiev, S; Alam, M; Putri, FA; Bastard, M; Docteur, W; Gottlieb, G; et al. (Oxford University Press, 2019-11-02)
      Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months.
    • Ensuring access to affordable, timely vaccines in emergencies

      Elder, K; Saitta, B; Tanja, D; Elder, G; Close, R; Scourse, R; Kahn, P; Scheele, S; Miriam, A; Erickson, E; et al. (WHO Press, 2019-10-28)
      Vaccination is an effective intervention to reduce disease, disability, death and health inequities worldwide. Over the last two decades, vaccines have become more accessible in low-income countries; however, significant gaps remain, particularly in humanitarian emergencies, where populations face increased risks of many diseases. In 2013, the World Health Organization (WHO) published Vaccination in acute humanitarian emergencies: a framework for decision-making, to provide guidance on which vaccines to prioritize during emergencies.1 However, substantial obstacles, especially high prices for new vaccines, hinder implementation of this framework and of critical vaccination activities in emergency settings. In response to these challenges, global health stakeholders held a series of consultations in 2016 and proposed a WHO-based mechanism, the Humanitarian Mechanism, for the rapid procurement of affordable vaccines during emergencies, to be used by nongovernmental organizations (NGOs), civil society organizations, United Nations (UN) agencies and governments. Here we present the background of the creation of the mechanism from the perspective of Médecins Sans Frontières (MSF), including a description of our past challenges in accessing affordable pneumococcal conjugate vaccine (PCV; Box 1), a critical vaccine during many emergencies. We then describe how the mechanism has so far facilitated access to more affordable PCV and outline steps that could increase its potential for saving lives.
    • Adherence and population pharmacokinetic properties of amodiaquine when used for seasonal malaria chemoprevention in African children

      Ding, J; Coldiron, ME; Assao, B; Guindo, O; Blessborn, D; Winterberg, M; Grais, RF; Koscalova, A; Langendorf, C; Tarning, J (American Society for Clinical Pharmacology and Therapeutics, 2019-10-25)
      Poor adherence to seasonal malaria chemoprevention (SMC) might affect the protective effectiveness of SMC. Here, we evaluated the population pharmacokinetic properties of amodiaquine and its active metabolite, desethylamodiaquine, in children receiving SMC under directly‐observed ideal conditions (n=136), and the adherence of SMC at an implementation phase in children participating in a case‐control study to evaluate SMC effectiveness (n=869). Amodiaquine and desethylamodiaquine concentration‐time profiles were described simultaneously by two‐compartment and three‐compartment disposition models, respectively. The developed methodology to evaluate adherence showed a sensitivity of 65‐71% when the first dose of SMC was directly observed and 71‐73% when no doses were observed in a routine programmatic setting. Adherence simulations and measured desethylamodiaquine concentrations in the case‐control children showed complete adherence (all doses taken) in less than 20% of children. This result suggests that more efforts are needed urgently to improve the adherence to SMC among children in this area.