Now showing items 41-60 of 2836

    • Clinical diagnostic evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria in an area receiving seasonal malaria chemoprevention in Niger

      Coldiron, M; Assao, B; Langendorf, C; Sayinzoga-Makombe, N; de la Tour, R; Piriou, E; Ciglenecki, I; Mumina, A; Guindo, O; Page, A-L; et al. (Springer Science and Business Media LLC, 2019-12-26)
      Background Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative. Methods A prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3–28 October, 2017) and during the low transmission season (28 January–31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season. Results In the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1–63.8) for the pLDH test and 57.4% (95% CI 51.5–63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1–71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3–95.0) for the pLDH test and 85.8% (95% CI 79.3–90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9–66.8) for the pLDH test and 61.9% (55.0–68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention. Conclusions The low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.
    • Clinical diagnostic evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria in an area receiving seasonal malaria chemoprevention in Niger.

      Coldiron, M; Assao, B; Langendorf, C; Sayinzoga-Makombe, N; Ciglenecki, I; de la Tour, R; Piriou, E; Bako, M; Mumina, A; Guindo, O; et al. (BioMed Central, 2019-12-26)
      BACKGROUND: Rapid diagnostic tests (RDT) for malaria are common, but their performance varies. Tests using histidine-rich protein 2 (HRP2) antigen are most common, and many have high sensitivity. HRP2 tests can remain positive for weeks after treatment, limiting their specificity and usefulness in high-transmission settings. Tests using Plasmodium lactate dehydrogenase (pLDH) have been less widely used but have higher specificity, mostly due to a much shorter time to become negative. METHODS: A prospective, health centre-based, diagnostic evaluation of two malaria RDTs was performed in rural Niger during the high malaria transmission season (3-28 October, 2017) and during the low transmission season (28 January-31 March, 2018). All children under 5 years of age presenting with fever (axillary temperature > 37.5 °C) or history of fever in the previous 24 h were eligible. Capillary blood was collected by finger prick. The SD Bioline HRP2 (catalog: 05FK50) and the CareStart pLDH(pan) (catalog: RMNM-02571) were performed in parallel, and thick and thin smears were prepared. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 279 children with microscopy-confirmed malaria during each transmission season. RESULTS: In the high season, the sensitivity of both tests was estimated at > 99%, but the specificity of both tests was lower: 58.0% (95% CI 52.1-63.8) for the pLDH test and 57.4% (95% CI 51.5-63.1) for the HRP2 test. The positive predictive value was 66.3% (95% CI 61.1-71.2) for both tests. In the low season, the sensitivity of both tests dropped: 91.0% (95% CI 85.3-95.0) for the pLDH test and 85.8% (95% CI 79.3-90.9) for the HRP2 test. The positive predictive value remained low for both tests in the low season: 60.5% (95% CI 53.9-66.8) for the pLDH test and 61.9% (55.0-68.4) for the HRP2 test. Performance was similar across different production lots, gender, age of the children, and, during the high season, time since the most recent distribution of seasonal malaria chemoprevention. CONCLUSIONS: The low specificity of the pLDH RDT in this setting was unexpected and is not easily explained. As the pLDH test continues to be introduced into new settings, the questions raised by this study will need to be addressed.
    • Knowledge, Awareness and Practices of Incident Cases of Dengue in Chandigarh

      Kaur, R; Rajvanshi, H (Advanced Research Publications, 2019-12-23)
      Introduction: Dengue is an endemic disease in India. Epidemics occur every year with incidence rising every year. Since 2010, Chandigarh has seen Dengue epidemics every year but the toll of reported confirmed cases has been very low. A study was undertaken to assess knowledge, awareness and practices among those who had already been diagnosed with dengue and followed up multiple times by Multipurpose Health Workers (MPHWs) at their homes. This study was conducted when both authors were post-graduate scholars at the Department of Public Health at Manipal Academy of Higher Education.Objective: To ascertain knowledge, awareness and practices regarding dengue among incident dengue cases of 2016 in Chandigarh. Methods: Retrospective Cohort study was conducted among the incident cases of dengue reported in 2016. The line list of cases was obtained from health department. Each household was visited once and face to face interviews were conducted with those willing to participate from January 2017 to March 2017. Using a modified WHO (World Health Organisation) questionnaire, 149 interviews were completed and analysed using descriptive analytical tools. Results: Data from the 149 interviews (57 males and 92 females) was used for primary analysis. Only 58.4% respondents were aware about dengue before diagnosis and 63.1% knew of its vector while only 10.1% were aware of the national programme and services available to them. Use of mosquito net was negligible (3.4%), even in rural areas. Screens on doors and windows were more common in urban area of Chandigarh. Conclusion: Since the study was conducted among incident cases, even after multiple visits conducted by MPHWs to the houses of these respondents, the knowledge regarding dengue was lower than expected.
    • GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India

      Isaakidis, P; Ferlazzo, G; Das, M; Pasupuleti, D; Sloan, S; Hossain, F; Kalon, S; Mansoor, H; Rao, S (MDPI AG, 2019-12-21)
      Abstract: Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
    • Barriers and solutions to finding rifampicin-resistant tuberculosis cases in older children and adolescents

      Mohr-Holland, E; Apolisi, I; Reuter, A; de Azevedo, V; Hill, J; Matthee, S; Seddon, JA; Isaakidis, P; Furin, J; Trivino-Duran, L (International Union Against Tuberculosis and Lung Disease, 2019-12-21)
      Little is known about the barriers to post-exposure management of rifampicin-resistant tuberculosis (RR-TB) in older children and adolescents. We report on implementation lessons from a pilot programme targeting household-exposed individuals aged 6–18 years in Khayelitsha, South Africa. Barriers included misperceptions regarding risk of exposure, multiple research and implementation stakeholders, additional workload for an overburdened healthcare system, logistical issues faced by families, and insufficient human and financial resources. Solutions to these barriers are possible, but creativity and persistence are required. Our experience can guide others looking to roll-out care for children and adolescents exposed to RR-TB.
    • Scaling up HIV viral load monitoring in Manicaland, Zimbabwe: challenges and opportunities from the field

      Nyagadza, B; Kudya, N; Mbofana, E; Masaka, S; Garone, D; Chen, CY; Mulingwa, A; Uzande, C; Isaakidis, P; Ndlovu, Z (International Union Against Tuberculosis and Lung Disease, 2019-12-21)
      Background: Demand for viral load (VL) monitoring is expected to increase; however, implementation of the multifaceted VL testing poses numerous challenges. We report experiences from Médecins Sans Frontiéres (MSF) and partners in the scale-up of HIV VL in collaboration with the Ministry of Health and Child Care (MoHCC) of Zimbabwe. Methods: A retrospective data review of routine reports from MSF-supported health facilities in Manicaland Province (Zimbabwe) was conducted. These secondary aggregate data were triangulated, and emerging themes of lessons learnt from VL monitoring were shared. Results: A VL testing coverage of 63% (5966/9456) was achieved among the 40 health facilities, together with a switch rate to second-line antiretroviral therapy (ART) of 46.4% (108/233). The key enablers to scaling-up the VL monitoring were well-equipped and supported VL laboratories, the operationalisation of the on-the-job clinical mentoring and systematic weaning off of better performing health facilities. Concerted efforts from different implementing partners and funders in the HIV programme, and close collaboration with MoHCC were pivotal. Conclusion: Our experience indicates that clinical mentoring is effective, and resulted in high VL testing coverage and up-skilling primary health care workers in VL monitoring. Attention must be focused on innovations for improving VL result utilisation, especially the identification and management of patients who fail ART.
    • GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India.

      Das, M; Pasupuleti, D; Rao, S; Sloan, S; Mansoor, H; Kalon, S; Hossain, F; Ferlazzo, G; Isaakidis, P (MDPI AG, 2019-12-21)
      Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015–August 2016 and b) April 2017–August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.
    • Standardised shorter regimens versus individualised longer regimens for multidrug-resistant TB

      Abidi, S; Achar, J; Neino, M; Bang, D; Benedetti, A; Brode, S; Campbell, J; Casas, E; Conradie, F; Dravniece, G; et al. (European Respiratory Society (ERS), 2019-12-20)
      We sought to compare the effectiveness of two WHO-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis: a standardised regimen of 9-12 months (the "shorter regimen"), and individualised regimens of ≥20 months ("longer regimens").We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR tuberculosis. We used propensity score matched, mixed-effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRD) for failure or relapse, death within 12 months of treatment initiation, and loss to follow-up.We included 2625/3378 (77.7%) individuals from 9 studies of shorter regimens, and 2717/13104 (20.7%) from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions: 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD, -0.15 95%CI: -0.17 to -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (0.02, 95%CI: 0 to 0.05), and greater in magnitude with baseline resistance to pyrazinamide (0.12, 95%CI: 0.07 to 0.16), prothionamide/ethionamide (0.07, 95%CI: -0.01 to 0.16), or ethambutol (0.09, 95%CI: 0.04 to 0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment as compared to individualised longer regimens, and with more failure/relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
    • Markers of sulfadoxine–pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention

      van Lenthe, M; van der Meulen, R; Okell, L; Piriou, E; Lassovski, M; Bakula, E; Badio, C; Roper, C; Bousema, T; Ouabo, A; et al. (Springer Science and Business Media LLC, 2019-12-18)
      Background Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap. Methods Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays. Results Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample. Conclusions The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.
    • “To die is better for me”, social suffering among Syrian refugees at a noncommunicable disease clinic in Jordan: A Qualitative Study

      Ansbro, E; Maconick, L; Ellithy, S; Jobanputra, K; Tarawneh, M; Roberts, B; MSF UK; London School of Hygiene and Tropical Medicine (Research Square, 2019-12-18)
      Background The conflict in Syria has required humanitarian agencies to implement primary-level services for non-communicable diseases (NCDs) in Jordan, given the high NCD burden amongst Syrian refugees; and to integrate mental health and psychosocial support into NCD services given their comorbidity and treatment interactions. However, no studies have explored the mental health needs of Syrian NCD patients. This paper aims to examine the interaction between physical and mental health of patients with NCDs at a Médecins Sans Frontières (MSF) clinic in Irbid, Jordan, in the context of social suffering. Methods This qualitative study involved sixteen semi-structured interviews with Syrian refugee and Jordanian patients and two focus groups with Syrian refugees attending MSF’s NCD services in Irbid, and eighteen semi-structured interviews with MSF clinical, managerial and administrative staff. These were conducted by research staff in August 2017 in Irbid, Amman and via Skype. Thematic analysis was used. Results Respondents describe immense suffering and clearly perceived the interconnectedness of their physical wellbeing, mental health and social circumstances, in keeping with Kleinman’s theory of social suffering. There was a ‘disconnect’ between staff and patients’ perceptions of the potential role of the NCD and mental health service in alleviating this suffering. Possible explanations identified included respondent’s low expectations of the ability of the service to impact on the root causes of their suffering, normalisation of distress, the prevailing biomedical view of mental ill-health among national clinicians and patients, and humanitarian actors’ own cultural standpoints. Conclusion NCD patients recognised the psychological dimensions of their illness but may not utilize clinic-based humanitarian mental health and psychosocial support services. Humanitarian agencies must engage with NCD patients to elicit their needs and design culturally relevant services.
    • Potential impact and cost-effectiveness of condomless-sex-concentrated PrEP in KwaZulu-Natal accounting for drug resistance

      Revill, Paul; Phillips, A; Cambiano, V; Johnson, L; Homan, R; Nakagawa, F; Meyer-Rath, G; Tanser, F; Rehle, T; Moyo, S; et al. (Oxford University Press (OUP), 2019-12-18)
      Abstract INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) in the form of tenofovir-disoproxil-fumarate/emtricitabine is being implemented in selected sites in South Africa. Addressing outstanding questions on PrEP cost-effectiveness can inform further implementation. METHODS: We calibrated an individual-based model to KwaZulu-Natal to predict the impact and cost-effectiveness of PrEP, with use concentrated in periods of condomless sex, accounting for effects on drug resistance. We consider (i) PrEP availability for adolescent-girls-and-young-women (aged 15-24; AGYW) and female sex workers (FSW), and (ii) availability for everyone aged 15-64. Our primary analysis represents a level of PrEP use hypothesized to be attainable by future PrEP programmes. RESULTS: In the context of PrEP use in adults aged 15-64 there was a predicted 33% reduction in incidence, and 36% reduction in women aged 15-24. PrEP was cost effective, including in a range of sensitivity analyses, although with substantially reduced (cost) effectiveness under a policy of ART initiation with efavirenz- rather than dolutegravir-based regimens due to PrEP undermining ART effectiveness by increasing HIV drug resistance. CONCLUSIONS: PrEP use concentrated during time periods of condomless sex has the potential to substantively impact HIV incidence and be cost-effective.
    • Markers of sulfadoxine-pyrimethamine resistance in Eastern Democratic Republic of Congo; implications for malaria chemoprevention.

      van Lenthe, M; van der Meulen, R; Lassovski, M; Ouabo, A; Bakula, E; Badio, C; Cibenda, D; Okell, L; Piriou, E; Grignard, L; et al. (BioMed Central, 2019-12-18)
      BACKGROUND: Sulfadoxine-pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap. METHODS: Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays. RESULTS: Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5-25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3-87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7-47.2%). The dhfr I164L mutation was found in one sample. CONCLUSIONS: The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.
    • Active and adaptive case finding to estimate therapeutic program coverage for severe acute malnutrition: a capture-recapture study

      Isanaka, S; Salou, H; Hedt-Guathier, B; Grais, R; Allen, B; Berthé, F; Salou, H (Springer Science and Business Media LLC, 2019-12-16)
      Background: Coverage is an important indicator to assess both the performance and effectiveness of public health programs. Recommended methods for coverage estimation for the treatment of severe acute malnutrition (SAM) can involve active and adaptive case finding (AACF), an informant-driven sampling procedure, for the identification of cases. However, as this procedure can yield a non-representative sample, exhaustive or near exhaustive case identification is needed for valid coverage estimation with AACF. Important uncertainty remains as to whether an adequate level of exhaustivity for valid coverage estimation can be ensured by AACF. Methods: We assessed the sensitivity of AACF and a census method using a capture-recapture design in northwestern Nigeria. Program coverage was estimated for each case finding procedure. Results: The sensitivity of AACF was 69.5% (95% CI: 59.8, 79.2) and 91.9% (95% CI: 85.1, 98.8) with census case finding. Program coverage was estimated to be 40.3% (95% CI 28.6, 52.0) using AACF, compared to 34.9% (95% CI 24.7, 45.2) using the census. Depending on the distribution of coverage among missed cases, AACF sensitivity of at least ≥70% was generally required for coverage estimation to remain within ±10% of the census estimate. Conclusion: Given the impact incomplete case finding and low sensitivity can have on coverage estimation in potentially non-representative samples, adequate attention and resources should be committed to ensure exhaustive or near exhaustive case finding
    • The politics of exclusion: fighting for patients with Kidney failure in Yemen’s War

      Heller Perarche, A; Fall, C; van Leeuwen, C; MSF London; MSF OCA; MSF USA (Oxford University Press (OUP), 2019-12-15)
      Background To contribute toward the dialogue on addressing non-communicable and chronic disease in humanitarian emergencies, this article will explore the experiences of Médecins Sans Frontières in attempting to find support for the haemodialysis network in Yemen. With the changing profile of the global disease burden and a broadening concept of emergency health needs to include chronic illness and disability, the aid sector has committed through the World Humanitarian Summit and the Sustainable Development Goals to leave no one behind and thus to meet the health needs of these previously excluded and highly vulnerable people. The civil war in Yemen compromised the medical supply chain supporting the health facilities providing dialysis for patients with end-stage renal disease. The article will critique the aid sector’s slow response to this issue and expose the gap between principles, commitments, and practice related to noncommunicable disease in emergencies. Method Following direct experiences from the authors as leaders in the aid response in Yemen, reviews of grey literature from aid and health actors in Yemen were conducted along with a review of literature and policy documents related to noncommunicable disease in emergency. Key informant interviews and press statements supported analysis and events that took place in the time span of roughly 4 years that frames this period of analysis. Results Examination of the impacted patient population, interviews, literature and documented events indicates that there is discord between policy, commitments stated by aid donors and practice. Conclusion The aid sector must use a more contextualised approach when designing programmes to manage the burden of non-communicable diseases in health contexts where crises occur, particularly for lifesaving forms of therapy. Aid agencies and the global health community must increase pressure on donors and implementing agencies to live up to their commitments to include these patient populations.
    • Trauma in the Kashmir Valley and the mediating effect of stressors of daily life on symptoms of posttraumatic stress disorder, depression and anxiety

      Housen, T; Lenglet, A; Shah, S; Sha, H; Richardson, A; Pintaldi, G; Shabnum, A; MSF OCA and MSF India (Springer Science and Business Media LLC, 2019-12-12)
      Background The negative psychological impact of living in a setting of protracted conflict has been well studied, however there is a recognized need to understand the role that non-conflict related factors have on mediating exposure to trauma and signs of psychological distress. Methods We used data from the 2015 Kashmir Mental Health Survey and conducted mediation analysis to assess the extent to which daily stressors mediated the effect of traumatic experiences on poor mental health outcomes. Outcomes of interest were probable diagnosis of anxiety, depression, or PTSD; measured using the pre-validated Hopkins Symptoms Checklist (HSCL-25) and the Harvard Trauma Questionnaire (HTQ). Results Total effect mediated were statistically significant but the proportions of effect mediated were found to be small in practical terms. Financial stress mediated 6.8% [95% Confidence Interval (CI) 6∙0–8∙4], 6.7% [CI 6.2–7∙7] and 3.6% [CI 3∙4–4∙0] of the effect of experiencing multiple traumaticogenic events on symptoms of anxiety, depression and PTSD, respectively. Family stress mediated 11.3% [CI 10.3–13.8], 10.3% [CI 9.5–11.9] and 6.1% [CI 5.7–6.7] of the effect of experiencing multiple traumatogenic events on symptoms of anxiety, depression and PTSD, respectively. Poor physical health mediated 10.0% [CI 9.1–12∙0], 7.2% [CI 6.6–8.2] and 4.0% [CI 3.8,4.4] of the effect of experiencing more than seven traumatic events on symptoms of anxiety, depression and PTSD, respectively. Conclusion Our findings highlight that not only do we need to move beyond a trauma-focussed approach to addressing psychological distress in populations affected by protracted conflict but we must also move beyond focussing on daily stressors as explanatory mediators.
    • A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

      Mulangu, S; Grais, R; Dodd, L; Follmann, D; Proschan, M; Davey, R; Mukadi, D; Lusakibanza, M (2019-12-12)
      BACKGROUND Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. METHODS We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase–polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. RESULTS A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. CONCLUSIONS Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.)
    • Peer Mentorship via Mobile Phones for Newly Diagnosed HIV-Positive Youths in Clinic Care in Khayelitsha, South Africa: Mixed Methods Study

      Hacking, D; Cassidy, T; Mgengwana-Mbakaza, Z; Boulle, A; Mathys, R; Runeyi, P; Duran, L (JMIR Publications Inc., 2019-12-10)
      Background: Youths in South Africa are poor utilizers of HIV health services. Medecins Sans Frontieres has been piloting youth-adapted services at a youth clinic in Khayelitsha, including a peer virtual mentorship program over mobile phones, piloted from March 2015 to May 2016. Objective: The objective of this study was to evaluate the effect of the peer mentorship program on youth engagement with HIV services and explore the acceptability of the program to both mentors and mentees. Methods: Antiretroviral initiation, retention in care (RIC), and viral load suppression were compared between youths engaged in the virtual mentorship program and two matched controls. In-depth interviews were also conducted for 5 mentors and 5 mentees to explore acceptability and impact of the program. Results: A total of 40 youths were recruited into the virtual mentorship program over the study period. Of these, data were obtained for 35 and 2 matched controls were randomly sampled for each. There was no difference in baseline demographics (eg, age, gender, and CD4 count). Mentees had increased antiretroviral initiation (28/35, 80% vs 30/70, 42% in matched controls) and viral load completion (28/35, 80% vs 32/70, 45%); however, no differences were found in viral load suppression or RIC at 6 or 12 months. Mentors reported being motivated to participate in the program because of previous personal struggles with HIV and a desire to help their peers. Mentees reported fears of disclosure and lack of acceptance of their status as barrier to accessing services, but they felt free to talk to their mentors, valued the mentorship program, and indicated a preference for phone calls. Conclusions: Peer mentorship in youths is acceptable to both mentors and mentees and appears to increase linkage to care and viral load completion rates.
    • Paediatric Buruli ulcer in Australia

      Walker, G; Friedman, D; Cooper, C; O'Brien, M; McDonald, A; Callan, P; O'Brien, D; MSF UK Manson Unit (2019-12-10)
      AIM: This study describes an Australian cohort of paediatric Buruli ulcer (BU) patients and compares them with adult BU patients. METHODS: Analysis of a prospective cohort of all BU cases managed at Barwon Health, Victoria, from 1 January 1998 to 31 May 2018 was performed. Children were defined as ≤15 years of age. RESULTS: A total of 565 patients were included: 52 (9.2%) children, 289 (51.2%) adults aged 16-64 years and 224 (39.6%) adults aged ≥65 years. Among children, half were female and the median age was 8.0 years (interquartile range 4.8-12.3 years). Six (11.5%) cases were diagnosed from 2001 to 2006, 14 (26.9%) from 2007 to 2012 and 32 (61.5%) from 2013 to 2018. Compared to adults, children had a significantly higher proportion of non-ulcerative lesions (32.7%, P < 0.001) and a higher proportion of severe lesions (26.9%, P < 0.01). The median duration of symptoms prior to diagnosis was shorter for children compared with adults aged 16-64 years (42 vs. 56 days, P = 0.04). Children were significantly less likely to experience antibiotic complications (6.1%) compared with adults (20.6%, P < 0.001), but had a significantly higher rate of paradoxical reactions (38.8%) compared with adults aged 16-64 (19.2%) (P < 0.001). Paradoxical reactions in children occurred significantly earlier than in adults (median 17 vs. 56 days, P < 0.01). Cure rates were similarly high for children compared to adults treated with antibiotics alone or with antibiotics and surgery. CONCLUSIONS: Paediatric BU cases in Australia are increasing and represent an important but stable proportion of Australian BU cohorts. Compared with adults, there are significant differences in clinical presentation and treatment outcomes.
    • Increased risk of acquisition and transmission of ESBL-producing Enterobacteriaceae in malnourished children exposed to amoxicillin

      Maataoui, N; Langendorf, C; Berthe, F; Grais, R; van Schaik, W; Isanaka, S; Clermont, O; Bayjanov, J; Andremont, A; Armand-Lefevre, Laurence; et al. (Oxford University Press (OUP) We regret that this article is behind a paywall., 2019-12-10)
      OBJECTIVES: Routine amoxicillin for children with uncomplicated severe acute malnutrition raises concerns of increasing antibiotic resistance. We performed an ancillary study nested within a double-blind, placebo-controlled trial in Niger testing the role of routine 7 day amoxicillin therapy in nutritional recovery of children 6 to 59 months of age with uncomplicated severe acute malnutrition. METHODS: We screened 472 children for rectal carriage of ESBL-producing Enterobacteriaceae (ESBL-E) as well as their household siblings under 5 years old, at baseline and Week 1 (W1) and Week 4 (W4) after start of therapy, and characterized strains by WGS. ClinicalTrials.gov: NCT01613547. RESULTS: Carriage in index children at baseline was similar in the amoxicillin and the placebo groups (33.8% versus 27.9%, P = 0.17). However, acquisition of ESBL-E in index children at W1 was higher in the amoxicillin group than in the placebo group (53.7% versus 32.2%, adjusted risk ratio = 2.29, P = 0.001). Among 209 index and sibling households possibly exposed to ESBL-E transmission, 16 (7.7%) had paired strains differing by ≤10 SNPs, suggesting a high probability of transmission. This was more frequent in households from the amoxicillin group than from the placebo group [11.5% (12/104) versus 3.8% (4/105), P = 0.04]. CONCLUSIONS: Among children exposed to amoxicillin, ESBL-E colonization was more frequent and the risk of transmission to siblings higher. Routine amoxicillin should be carefully balanced with the risks associated with ESBL-E colonization.
    • A reflection on case reporting in resource-limited settings

      Wind, A (Oxford University Press (OUP), 2019-12-09)
      In 2015, I was in the Democratic Republic of the Congo (DRC), working as a pediatrician with Médecins Sans Frontières (MSF). As had been the case in my two previous assignments with MSF, I encountered many interesting and challenging cases—cases that I had never experienced prior to working in resource limited settings. Contrary to when I work in the USA and have access to extensive laboratory exams and diagnostic testing, in our hospital in the DRC, no such tools were available, and thus I needed to use a whole new level of clinical skills and deductive reasoning. To make clinical management even more challenging, I rarely saw these types of cases written about or published in the medical literature. I was discouraged that although these clinical examples were perfect fodder for medical case discussions, they did not have the ‘components’ required for a traditional case report. In frustration, I wrote the following: ‘The reason why we, those working in “resource limited settings”, do not often attempt to publish case reports is because we don’t often find an answer. We think that published articles and case reports should be neat and clean. That students or colleagues should be able to read a mystery case, try to solve the puzzle, and at the end be rewarded with an answer brought about by some obscure lab or radiology report. But that’s not what happens. The world of medicine in resource limited settings isn’t neat and clean. It’s frustrating and messy. Mystifying and sad. You can come up with a million differentials but ultimately the child, because of, or in despite of, your chosen treatment, makes it. Or doesn’t make it. And you never get an answer. You don’t learn. And you can try to look in the literature, but the research will talk about IGF1 and MRI and calcium. I can’t even get a cal.ci.um. And so, the mystery disease leads to a mystery death and you are left feeling powerless. And there is not even a take home message.’ I am excited that now with the Oxford Medical Case Reports collaboration, there is a platform to start regaining some power, to start creating a take-home message. There is a platform for collaboration amongst all of us medical professionals working in resource limited settings—a platform to share these unique cases to perhaps discover that they are not so unique at all. They are just not published.