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

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  • 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.
  • 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.
  • 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.
  • Feasibility of antiretroviral therapy initiation under the treat‐all policy under routine conditions: a prospective cohort study from Eswatini

    Kerschberger, B; Jobanputra, K; Schomaker, M; Kabore, SM; Teck, R; Mabhena, E; Lukhele, N; Rusch, B; Boulle, A; Ciglenecki, I (Wiley Open Access, 2019-10-24)
    Introduction The World Health Organization recommends the Treat‐All policy of immediate antiretroviral therapy (ART) initiation, but questions persist about its feasibility in resource‐poor settings. We assessed the feasibility of Treat‐All compared with standard of care (SOC) under routine conditions. Methods This prospective cohort study from southern Eswatini followed adults from HIV care enrolment to ART initiation. Between October 2014 and March 2016, Treat‐All was offered in one health zone and SOC according to the CD4 350 and 500 cells/mm3 treatment eligibility thresholds in the neighbouring health zone, each of which comprised one secondary and eight primary care facilities. We used Kaplan–Meier estimates, multivariate flexible parametric survival models and standardized survival curves to compare ART initiation between the two interventions. Results Of the 1726 (57.3%) patients enrolled under Treat‐All and 1287 (42.7%) under SOC, cumulative three‐month ART initiation was higher under Treat‐All (91%) than SOC (74%; p < 0.001) with a median time to ART of 1 (IQR 0 to 14) and 10 (IQR 2 to 117) days respectively. Under Treat‐All, ART initiation was higher in pregnant women (vs. non‐pregnant women: adjusted hazard ratio (aHR) 1.96, 95% confidence interval (CI) 1.70 to 2.26), those with secondary education (vs. no formal education: aHR 1.48, 95% CI 1.12 to 1.95), and patients with an HIV‐positive diagnosis before care enrolment (aHR 1.22, 95% CI 1.10 to 1.36). ART initiation was lower in patients attending secondary care facilities (aHR 0.64, 95% CI 0.58 to 0.72) and for CD4 351 to 500 when compared with CD4 201 to 350 cells/mm3 (aHR 0.84, 95% CI 0.72 to 1.00). ART initiation varied over time for TB cases, with lower hazard during the first two weeks after HIV care enrolment and higher hazards thereafter. Of patients with advanced HIV disease (n = 1085; 36.0%), crude 3‐month ART initiation was similar in both interventions (91% to 92%) although Treat‐All initiated patients more quickly during the first month after HIV care enrolment. Conclusions ART initiation was high under Treat‐All and without evidence of de‐prioritization of patients with advanced HIV disease. Additional studies are needed to understand the long‐term impact of Treat‐All on patient outcomes.
  • New ways to measure the effects of armed conflict in civilian population

    Kadir, A; Garcia, DM; Romero, F (Elsevier, 2019-10-24)
  • Introduction of a standardised protocol, including systematic use of tranexamic acid, for management of severe adult trauma patients in a low-resource setting: the MSF experience from Port-au-Prince, Haiti

    Jachetti, A; Massenat, RB; Edema, N; Woolley, SC; Benedetti, G; Van Den Bergh, R; Trelles, M (BioMed Central, 2019-10-18)
    Background Bleeding is an important cause of death in trauma victims. In 2010, the CRASH-2 study, a multicentre randomized control trial on the effect of tranexamic acid (TXA) administration to trauma patients with suspected significant bleeding, reported a decreased mortality in randomized patients compared to placebo. Currently, no evidence on the use of TXA in humanitarian, low-resource settings is available. We aimed to measure the hospital outcomes of adult patients with severe traumatic bleeding in the Médecins Sans Frontières Tabarre Trauma Centre in Port-au-Prince, Haiti, before and after the implementation of a Massive Haemorrhage protocol including systematic early administration of TXA. Methods Patients admitted over comparable periods of four months (December2015- March2016 and December2016 - March2017) before and after the implementation of the Massive Haemorrhage protocol were investigated. Included patients had blunt or penetrating trauma, a South Africa Triage Score ≥ 7, were aged 18–65 years and were admitted within 3 h from the traumatic event. Measured outcomes were hospital mortality and early mortality rates, in-hospital time to discharge and time to discharge from intensive care unit. Results One-hundred and sixteen patients met inclusion criteria. Patients treated after the introduction of the Massive Haemorrhage protocol had about 70% less chance of death during hospitalization compared to the group “before” (adjusted odds ratio 0.3, 95%confidence interval 0.1–0.8). They also had a significantly shorter hospital length of stay (p = 0.02). Conclusions Implementing a Massive Haemorrhage protocol including early administration of TXA was associated with the reduced mortality and hospital stay of severe adult blunt and penetrating trauma patients in a context with poor resources and limited availability of blood products.
  • A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy.

    Beer, EN; Rao, VB (The Public Library of Science, 2019-10-16)
    Monkeypox is a vesicular-pustular illness that carries a secondary attack rate in the order of 10% in contacts unvaccinated against smallpox. Case fatality rates range from 1 to 11%, but scarring and other sequelae are common in survivors. It continues to cause outbreaks in remote populations in Central and West Africa, in areas with poor access and weakened or disrupted surveillance capacity and information networks. Recent outbreaks in Nigeria (2017-18) and Cameroon (2018) have occurred where monkeypox has not been reported for over 20 years. This has prompted concerns over whether there have been changes in the biology and epidemiology of the disease that may in turn have implications for how outbreaks and cases should best be managed. A systematic review was carried out to examine reported data on human monkeypox outbreaks over time, and to identify if and how epidemiology has changed. Published and grey literature were critically analysed, and data extracted to inform recommendations on outbreak response, use of case definitions and public health advice. The level of detail, validity of data, geographical coverage and consistency of reporting varied considerably across the 71 monkeypox outbreak documents obtained. An increase in cases reported over time was supported by literature from the Democratic Republic of Congo (DRC). Data were insufficient to measure trends in secondary attack rates and case fatality rates. Phylogenetic analyses consistently identify two strains of the virus without evidence of emergence of a new strain. Understanding of monkeypox virulence with regard to clinical presentation by strain is minimal, with infrequent sample collection and laboratory analysis. A variety of clinical and surveillance case definitions are described in the literature: two definitions have been formally evaluated and showed high sensitivity but low specificity. These were specific to a Congo-Basin (CB) strain-affected area of the DRC where they were used. Evidence on use of antibiotics for prophylaxis against secondary cutaneous infection is anecdotal and limited. Current evidence suggests there has been an increase in total monkeypox cases reported by year in the DRC irrespective of advancements in the national Integrated Disease Surveillance and Response (IDSR) system. There has been a marked increase in number of individual monkeypox outbreak reports, from outside the DRC in between 2010 and 2018, particularly in the Central African Republic (CAR) although this does not necessarily indicate an increase in annual cases over time in these areas. The geographical pattern reported in the Nigeria outbreak suggests a possible new and widespread zoonotic reservoir requiring further investigation and research. With regards to outbreak response, increased attention is warranted for high-risk patient groups, and nosocomial transmission risks. The animal reservoir remains unknown and there is a dearth of literature informing case management and successful outbreak response strategies. Up-to-date complete, consistent and longer-term research is sorely needed to inform and guide evidence-based response and management of monkeypox outbreaks.
  • Evaluation of OMNIgene® SPUTUM and ethanol reagent for preservation of sputum prior to Xpert and culture testing in Uganda.

    Ardizzoni, E; Orikiriza, P; Ssuuna, C; Nyehangane, D; Gumsboga, M; Taremwa, IM; Turyashemererwa, E; Mwanga-Amumpaire, J; Langendorf, C; Bonnet, M (American Society for Microbiology, 2019-10-16)
    Background: Xpert MTB/RIF (Xpert) and culture are the most reliable methods for tuberculosis diagnosis but are still poorly accessible in many low resource countries. We aimed to assess the effect of OMNIgene® SPUTUM (OM-S) and ethanol in preserving sputum for Xpert and OM-S for mycobacteria growth indicator tube (MGIT) testing over a period of 15 and 8 days respectively. Methods: Sputum were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on day 0, 7 and 15 days without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days. Results: A total of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using Day 0 as reference, untreated samples stored for 7 and 15 days showed concordance of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordance was 46/48(95.8%) and 47/48(97.9%), while ethanol was 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordance between untreated and OM-S treated samples was 21/41(51.2%) at Day 0 and 21/44(47.7%) at day8. Conclusions: Xpert equally detected TB in OM-S treated and untreated samples up to 15 days but showed slightly lower detection in ethanol treated samples. Among OM-S treated samples, MGIT positivity was significantly lower compared to untreated samples at both time-points.
  • Should urine-LAM tests be used in TB symptomatic HIV-positive patients when no CD4 count is available? A prospective observational cohort study from Malawi

    Huerga, H; Mathabire, SR; Bastard, M; Dimba, A; Kamba, C; Amoros, I; Szumilin, E (Lippincott, Williams & Wilkins, 2019-10-16)
    Background: Current eligibility criteria for urine lateral-flow-lipoarabinomannan assay (LF-LAM) in ambulatory, HIV-positive patients rely on the CD4 count. We investigated the diagnostic yield of LF-LAM and the 6-month mortality in ambulatory, TB symptomatic, HIV-positive patients regardless of their CD4 count. Methods: We conducted a prospective, observational study that included all ambulatory, >15-year-old, TB symptomatic (cough, weight loss, fever, or night sweats) HIV-positive patients presenting at 4 health facilities in Malawi. Patients received a clinical examination and were requested urine LF-LAM, sputum microscopy and Xpert MTB/RIF. TB was defined as bacteriologically confirmed if Xpert was positive. Results: Of 485 patients included, 171 (35.3%) had a CD4<200 and 32 (7.2%) were seriously ill. Median CD4 count was 341 cells/µL (IQR: 129-256). LAM was positive in 24.9% patients with CD4<200 (50% LAM Grades 2-4) and 12.5% with CD4≥200 (12.8% LAM Grades 2-4). Xpert was positive in 14.1% (44/312). Among Xpert-positive patients, LAM-positivity was: 56.7% (CD4<200) and 42.9% (CD4≥200), p=0.393. Of the patients without an Xpert result, 13.4% (23/172) were LAM-positive (i.e. potentially missed patients). Overall mortality was 9.2% (44/478). More pronounced LAM-positive patients had higher mortality than LAM-negative (Grades 2-4: 36.0%; Grade 1: 9.1%; Negative: 7.4%; p<0.001). LAM-positive patients with CD4<200 cells/µL had higher risk of mortality than LAM-negatives (aHR:3.2, 95CI:1.4-7.2, p=0.006), particularly those with LAM Grades 2-4 (aHR:4.9, 95CI:1.8-13.3, p=0.002). Conclusions: Urine-LAM testing can be useful for TB diagnosis in HIV-positive TB-symptomatic patients with no CD4 cell count. LAM grade can identify patients at higher risk of death in this situation.
  • Feasibility of using Determine TB-LAM to diagnose tuberculosis in HIV-positive patients in programmatic conditions: a multisite study.

    Mathabire Rucker, SC; Cossa, L; Harrison, RE; Mpunga, J; Lobo, S; Kisaka Kimupelenge, P; Mandar Kol'Ampwe, F; Amoros Quiles, I; Molfino, L; Szumilin, E; et al. (Taylor & Francis, 2019-10-15)
    Background: Determine TB-LAM is a urine-based point-of-care assay for diagnosis of tuberculosis (TB). Objective: To assess the feasibility of using LAM to diagnose TB in adult HIV-positive patients in resource-limited settings. Methods: We performed a multi-centric mixed-methods cross-sectional descriptive study in the Democratic Republic of Congo, Malawi, and Mozambique. We used the study and program monitoring tools to estimate user workload, turn-around time (TAT), and proportion of patients with LAM and sputum-based results. We conducted semi-structured interviews to assess the user acceptability of the LAM. Results: The duration of the LAM testing activity per patient was 27 min (IQR 26-29); staff continued with other duties whilst waiting for the result. More patients had a LAM versus a sputum-based result: 168/213 (78.9%) vs 77/213 (36.1%), p < 0.001 in DRC; 691/695 (99.4%) vs 429/695 (61.7%), p < 0.001 in Malawi; and 646/647 (99.8%) vs 262/647 (40.5%), p < 0.001 in Mozambique. The median TAT in minutes when LAM was performed in the consultation room was 75 (IQR 45-188) in DRC, 29 (IQR 27-39) in Malawi, and 36 (IQR 35-41) in Mozambique. In comparison, the overall median TAT for sputum-based tests (smear or GeneXpert) was 2 (IQR 1-3) days. The median time to the first anti-TB drug dose for LAM-positive patients was 155 (IQR 90-504) minutes in DRC and 90 (IQR 60-117) minutes in Mozambique. The overall inter-reader agreement for the interpretation of the LAM result as positive or negative was 98.9%, kappa 0.97 (95%CI 0.96-0.99). Overall, LAM users found the test easy to perform. Major concerns were use of the reading card and the prior requirement of CD4 results before LAM testing. Conclusion: It is feasible to implement the LAM test in low resource settings. The short TAT permitted same day initiation of TB treatment for LAM-positive patients.
  • Factors influencing participation in an Ebola vaccine trial among front-line workers in Guinea

    Grantz, KH; Claudot, C; Kambala, M; Kouyate, M; Soumah, A; Boum, Y; Juan-Giner, A; Jemmy, JP; Cummings, DAT; Grais, RF (Elsevier, 2019-10-14)
    Background Alongside the clinical aspects of the immunogenicity and safety trial of an Ebola vaccine deployed among front-line workers, a qualitative study was conducted to describe motivations behind individuals’ decisions to participate – or not to participate – in the study. Methods In July and August 2015, focus group discussions and semi-structured individual interviews were conducted in Conakry, Guinea. Individuals were eligible for the qualitative study if they met the inclusion criteria of the immunogenicity and safety study irrespective of their participation. Surveys were also conducted among several institution and department heads of staff included in the study as well as vaccine trial staff members. Discussion and interview transcripts were analyzed using content thematic analysis. Results Interviews and focus groups were conducted among 110 persons, of whom about two-thirds (67%) participated in the vaccine trial. There was at least one group interview conducted at each participating trial site, along with numerous formal and informal interviews and conversations through the enrollment period. Participants were often motivated by a desire to save and protect themselves and others, contribute to scientific progress, or lead by example. Non-participants expressed concerns regarding the risk and costs of participation, particularly the fear of unknown side effects following vaccination, and distrust or fear of stigmatization. Conclusions Despite the unique nature of the 2014–2015 Ebola outbreak, front-line workers employed much of the same logic when choosing to participate as in other clinical trials in similar settings. Special consideration should be given to addressing perceived inequity, misunderstanding, and mistrust among the target populations in future trials.
  • Hand hygiene compliance and environmental contamination with gram-negative bacilli in a rural hospital in Madarounfa, Niger

    Tang, K; Berthe, F; Nackers, F; Hanson, K; Mambula, C; Langendorf, C; Marquer, C; Isanaka, S (Oxford University Press, 2019-10-14)
    Background Healthcare-associated infections pose a major, yet often preventable risk to patient safety. Poor hand hygiene among healthcare personnel and unsanitary hospital environments may contribute to this risk in low-income settings. We aimed to describe hand hygiene behaviour and environmental contamination by season in a rural, sub-Saharan African hospital setting. Methods We conducted a concurrent triangulation mixed-methods study combining three types of data at a hospital in Madarounfa, Niger. Hand hygiene observations among healthcare personnel during two seasons contributed quantitative data describing hand hygiene frequency and its variability in relation to seasonal changes in caseload. Semistructured interviews with healthcare personnel contributed qualitative data on knowledge, attitudes and barriers to hand hygiene. Biweekly environmental samples evaluated microbial contamination from October 2016 to December 2017. Triangulation identified convergences, complements and contradictions across results. Results Hand hygiene compliance, or the proportion of actions (handrubbing or handwashing) performed out of all actions required, was low (11% during non-peak and 36% during peak caseload seasons). Interviews with healthcare personnel suggesting good general knowledge of hand hygiene contradicted the low hand hygiene compliance. However, compliance by healthcare activity was convergent with poor knowledge of precise hand hygiene steps and the motivation to prevent personal acquisition of infection identified during interviews. Contamination of environmental samples with gram-negative bacilli was high (45%), with the highest rates of contamination observed during the peak caseload season. Conclusion Low hand hygiene compliance coupled with high contamination rates of hospital environments may increase the risk of hospital-acquired infections in sub-Saharan African settings.
  • "With every passing day I feel like a candle, melting little by little." experiences of long-term displacement amongst Syrian refugees in Shatila, Lebanon.

    Syam, H; Venables, E; Sousse, B; Severy, N; Saavedra, L; Kazour, F (BioMed Central, 2019-10-10)
    BACKGROUND: Long term displacement and exposure to challenging living conditions can influence family dynamics; gender roles; violence at home and in the community and mental well-being. This qualitative study explores these issues as perceived by Syrian refugees who have been living in Shatila, a Palestinian camp in South Beirut, Lebanon, for at least 2 years. METHODS: Twenty eight in-depth interviews with men and women were conducted between February and June 2018. Women were recipients of mental health services, and men were recruited from the local community. Interviews were conducted in Arabic, translated, transcribed, coded and analysed using thematic content analysis. RESULTS: Our results show patterns of harsh living conditions similar to those described earlier in the course of the Syrian refugee crisis. Lack of infrastructure, overcrowding, cramped rooms and violence were all reported. Participants also described a lack of social support, discrimination and harassment within the host community, as well as limited social support networks within their own Syrian refugee community. Family dynamics were affected by the increased responsibilities on men, women and children; with additional economic and employment demands on men, women assuming the roles of 'mother and father' and children having to work and contribute to the household. Participants discussed several types of violence, including parental violence against children and violence in the community. Violence against women was also reported. Reported mental health issues included depression, anxiety, sadness, frustration, hopelessness, self-neglect and a loss of sense of self and self-worth. Some participants expressed a wish to die. CONCLUSIONS: This study describes experiences of changing gender roles, family dynamics, violence and mental health after long-term displacement in in Shatila camp, South Beirut as perceived by Syrian refugees. A lack of safety and security coupled with economic hardship rendered refugees even more susceptible to exploitation and harassment. Parental violence was the most commonly reported type of domestic violence.
  • Failure of an Innovative Low-Cost, Noninvasive Thermotherapy Device for Treating Cutaneous Leishmaniasis Caused by in Pakistan.

    Kamink, S; Abdi, A; Kamau, C; Ashraf, S; Ansari, MA; Qureshi, NA; Schallig, H; Grobusch, MB; Fernhout, J; Ritmeijer, K (The American Society of Tropical Medicine and Hygiene, 2019-10-07)
    Cutaneous leishmaniasis (CL), a neglected parasitic skin disease, is endemic in Pakistan, where Leishmania tropica and Leishmania major are the causative protozoan species. Standard treatment with antimonial injections is long, painful, and costly; has toxic side effects; and is not always available in public hospitals. Small pilot studies have previously evaluated a low-cost and noninvasive hand-held exothermic crystallization thermotherapy (HECT-CL) device. We aimed to further establish the effectiveness, safety, and feasibility of HECT-CL in L. tropica. In a prospective observational study, patients with parasitological confirmation of CL were treated using the HECT-CL heat pack for 3 minutes with an initial temperature of 52-53°C for 7 consecutive days. Dried blood spot samples were taken for species identification by PCR. Effectiveness was assessed by using medical photographs and measurements of the lesion size at baseline and subsequent follow-up visits, for up to 180 days. We intended to enroll 317 patients. The HECT-CL treatment was easy to apply and well tolerated. Species identification demonstrated the presence of L. tropica. Interim analysis of 56 patients showed a failure rate of 91% at follow-up (median 45 days after treatment, interquartile range 30-60 days). Enrollment of patients was prematurely suspended because of futility. This study showed a high failure rate for HECT-CL thermotherapy in this setting. Leishmania tropica is known to be less sensitive to antileishmanial drugs, more temperature-resistant, and spontaneous healing is slower than that in L. major. More research is needed to identify low-cost, effective, and more patient-friendly treatment for L. tropica.
  • Stuck in the middle: a systematic review of authorship in collaborative health research in Africa, 2014–2016

    Hedt-Gauthier, BL; Jeufack, HM; Neufeld, NH; Alem, A; Sauer, S; Odhiambo, J; Boum, Y; Shuchman, M; Volmink, J (BMJ Publishing Group, 2019-10-01)
    Background Collaborations are often a cornerstone of global health research. Power dynamics can shape if and how local researchers are included in manuscripts. This article investigates how international collaborations affect the representation of local authors, overall and in first and last author positions, in African health research. Methods We extracted papers on ‘health’ in sub-Saharan Africa indexed in PubMed and published between 2014 and 2016. The author’s affiliation was used to classify the individual as from the country of the paper’s focus, from another African country, from Europe, from the USA/Canada or from another locale. Authors classified as from the USA/Canada were further subclassified if the author was from a top US university. In primary analyses, individuals with multiple affiliations were presumed to be from a high-income country if they contained any affiliation from a high-income country. In sensitivity analyses, these individuals were presumed to be from an African country if they contained any affiliation an African country. Differences in paper characteristics and representation of local coauthors are compared by collaborative type using χ² tests. Results Of the 7100 articles identified, 68.3% included collaborators from the USA, Canada, Europe and/or another African country. 54.0% of all 43 429 authors and 52.9% of 7100 first authors were from the country of the paper’s focus. Representation dropped if any collaborators were from USA, Canada or Europe with the lowest representation for collaborators from top US universities—for these papers, 41.3% of all authors and 23.0% of first authors were from country of paper’s focus. Local representation was highest with collaborators from another African country. 13.5% of all papers had no local coauthors. Discussion Individuals, institutions and funders from high-income countries should challenge persistent power differentials in global health research. South-South collaborations can help African researchers expand technical expertise while maintaining presence on the resulting research.
  • What is the best culture conversion prognostic marker for patients treated for multidrug-resistant tuberculosis?

    Bastard, M; Sanchez-Padilla, E; Hayrapetyan, A; Kimenye, K; Khurkhumal, S; Dlamini, T; Fadul Perez, S; Telnov, A; Hewison, C; Varaine, F; et al. (International Union Against Tuberculosis and Lung Disease, 2019-10-01)
    INTRODUCTION: Identification of good prognostic marker for tuberculosis (TB) treatment response is a necessary step on the path towards a surrogate marker to reduce TB trial duration. METHODS: We performed a retrospective analysis on routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture conversion, defined as two consecutive negative cultures, was assessed, and performance of culture conversion at Month 2 and Month 6 to predict treatment success were explored. To explore factors associated with positive predicted value (PPV) and the specificity of culture conversion, a multinomial logistic regression was fitted. RESULTS: This study included 634 patients: 68.5% were males; the median age was 35 years, 75.2% were previously treated for TB, 59.4% were resistant only to isoniazid and rifampicin and 18.1% resistant to fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while specificity was much higher for culture conversion at Month 2: 91.3% (95%CI 86.1–95.1). PPV of culture conversion at Month 2 did not vary strongly according to patients' characteristics, while specificity was slightly higher among patients with fluoroquinolone-resistant strains. CONCLUSION: Culture conversion at Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the advantage of using an earlier marker, further evaluation as a surrogate marker is warranted to shorten TB trials.
  • Who is telling the story? A systematic review of authorship for infectious disease research conducted in Africa, 1980–2016

    Mbaye, R; Gebeyehu, R; Hossmann, S; Mbarga, N; Bih-Neh, E; Eteki, L; Thelma, OA; Oyerinde, A; Kiti, G; Mburu, Y; et al. (BMJ Publishing Group, 2019-10-01)
    Introduction Africa contributes little to the biomedical literature despite its high burden of infectious diseases. Global health research partnerships aimed at addressing Africa-endemic disease may be polarised. Therefore, we assessed the contribution of researchers in Africa to research on six infectious diseases. Methods We reviewed publications on HIV and malaria (2013–2016), tuberculosis (2014–2016), salmonellosis, Ebola haemorrhagic fever and Buruli ulcer disease (1980–2016) conducted in Africa and indexed in the PubMed database using Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Papers reporting original research done in Africa with at least one laboratory test performed on biological samples were included. We studied African author proportion and placement per study type, disease, funding, study country and lingua franca. Results We included 1182 of 2871 retrieved articles that met the inclusion criteria. Of these, 1109 (93.2%) had at least one Africa-based author, 552 (49.8%) had an African first author and 41.3% (n=458) an African last author. Papers on salmonellosis and tuberculosis had a higher proportion of African last authors (p<0.001) compared with the other diseases. Most of African first and last authors had an affiliation from an Anglophone country. HIV, malaria, tuberculosis and Ebola had the most extramurally funded studies (≥70%), but less than 10% of the acknowledged funding was from an African funder. Conclusion African researchers are under-represented in first and last authorship positions in papers published from research done in Africa. This calls for greater investment in capacity building and equitable research partnerships at every level of the global health community.

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