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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  • Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan.

    du Cros, Philipp; Khamraev, Atadjan; Tigay, Zinaida; Abdrasuliev, Tleubergen; Greig, Jane; Cooke, Graham; Herboczek, Krzysztof; Pylypenko, Tanya; Berry, Catherine; Ronnachit, Amrita; et al. (2021-02-08)
    Background In 2016, World Health Organization guidelines conditionally recommended standardised shorter 9–12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan. Methods Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion. Results Of 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8–44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression. Conclusions Overall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility.
  • Ethics of emerging infectious disease outbreak responses: Using Ebola virus disease as a case study of limited resource allocation.

    Nichol, AA; Antierens, A (Public Library of Science, 2021-02-02)
    Emerging infectious diseases such as Ebola Virus Disease (EVD), Nipah Virus Encephalitis and Lassa fever pose significant epidemic threats. Responses to emerging infectious disease outbreaks frequently occur in resource-constrained regions and under high pressure to quickly contain the outbreak prior to potential spread. As seen in the 2020 EVD outbreaks in the Democratic Republic of Congo and the current COVID-19 pandemic, there is a continued need to evaluate and address the ethical challenges that arise in the high stakes environment of an emerging infectious disease outbreak response. The research presented here provides analysis of the ethical challenges with regard to allocation of limited resources, particularly experimental therapeutics, using the 2013-2016 EVD outbreak in West Africa as a case study. In-depth semi-structured interviews were conducted with senior healthcare personnel (n = 16) from international humanitarian aid organizations intimately engaged in the 2013-2016 EVD outbreak response in West Africa. Interviews were recorded in private setting, transcribed, and iteratively coded using grounded theory methodology. A majority of respondents indicated a clear propensity to adopt an ethical framework of guiding principles for international responses to emerging infectious disease outbreaks. Respondents agreed that prioritization of frontline workers' access to experimental therapeutics was warranted based on a principle of reciprocity. There was widespread acceptance of adaptive trial designs and greater trial transparency in providing access to experimental therapeutics. Many respondents also emphasized the importance of community engagement in limited resource allocation scheme design and culturally appropriate informed consent procedures. The study results inform a potential ethical framework of guiding principles based on the interview participants' insights to be adopted by international response organizations and their healthcare workers in the face of allocating limited resources such as experimental therapeutics in future emerging infectious disease outbreaks to ease the moral burden of individual healthcare providers.
  • Delivering health and nutrition interventions for women and children in different conflict contexts: a framework for decision making on what, when, and how.

    Gaffey, MF; Waldman, RJ; Blanchet, K; Amsalu, R; Capobianco, E; Ho, LS; Khara, T; Garcia, DM; Aboubaker, S; Ashorn, P; et al. (Elsevier, 2021-01-24)
    Existing global guidance for addressing women's and children's health and nutrition in humanitarian crises is not sufficiently contextualised for conflict settings specifically, reflecting the still-limited evidence that is available from such settings. As a preliminary step towards filling this guidance gap, we propose a conflict-specific framework that aims to guide decision makers focused on the health and nutrition of women and children affected by conflict to prioritise interventions that would address the major causes of mortality and morbidity among women and children in their particular settings and that could also be feasibly delivered in those settings. Assessing local needs, identifying relevant interventions from among those already recommended for humanitarian settings or universally, and assessing the contextual feasibility of delivery for each candidate intervention are key steps in the framework. We illustratively apply the proposed decision making framework to show what a framework-guided selection of priority interventions might look like in three hypothetical conflict contexts that differ in terms of levels of insecurity and patterns of population displacement. In doing so, we aim to catalyse further iteration and eventual field-testing of such a decision making framework by local, national, and international organisations and agencies involved in the humanitarian health response for women and children affected by conflict.
  • Behavioural interventions to address rational use of antibiotics in outpatient settings of low‐income and lower‐middle‐income countries

    Nair, MM; Mahajan, E; Burza, S; Zeegers, MP (Wiley, 2021-01-16)
    Objectives To explore the current evidence on interventions to influence antibiotic prescribing behaviour of health professionals in outpatient settings in low‐income and lower‐middle‐income countries, an underrepresented area in the literature. Methods The systematic review protocol for this study was registered in PROSPERO (CRD42020170504). We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies relating to antibiotic prescribing of health professionals in outpatient settings in low‐income and lower‐middle‐income countries. Behavioural interventions were classified as persuasive, enabling, restrictive, structural or bundle (mix of different interventions). In total, 3,514 abstracts were screened and 42 studies were selected for full‐text review, with 13 studies included in the final narrative synthesis. Results Of the 13 included studies, five were conducted in Vietnam, two in Sudan, two in Tanzania, two in India and two in Kenya. All studies were conducted in the outpatient or ambulatory setting: eight took place in primary health centres, two in private clinics and three in pharmacies. Our review found that enabling or educational interventions alone may not be sufficient to overcome the ingrained incentives to link revenue generation to sales of antibiotics, and hence, their inappropriate prescription or misuse. Bundle interventions appear to be very effective at changing prescription behaviour among healthcare providers, including drug sellers and pharmacists. Conclusions Multi‐faceted bundle interventions that combine regulation enforcement with face‐to‐face education and peer influence may be more effective than educational interventions alone at curbing inappropriate antibiotic use.
  • Traumatic Injuries are the Main Indication for Limb Amputations During and After Humanitarian Crises

    Naidu, P; Dominguez, LB; Trelles, M; Chu, KM (Springer, 2021-01-15)
    Background Populations at risk during humanitarian crises can suffer traumatic injuries or have medical conditions that result in the need for limb amputation (LA). The objectives of this study were to describe the indications for and associations with LA during and after humanitarian crises in surgical projects supported by Médecins Sans Frontières (MSF). Methods MSF-Operational Center Brussels data from January 1, 2008, to December 31, 2017, were analyzed. Surgical projects were classified into (annual) periods of crises and post-crises. Indications were classified into trauma (intentional and unintentional) and non-trauma (medical). Associations with LA were also reported. Results MSF-OCB performed 936 amputations in 17 countries over the 10-year study period. 706 (75%) patients were male and the median age was 27 years (interquartile range 17–41 years). Six hundred and twenty-one (66%) LA were performed during crisis periods, 501 (53%) during conflict and 119 (13%) post-natural disaster. There were 316 (34%) LA in post-crisis periods. Overall, trauma was the predominant indication (n = 756, 81%) and accounted for significantly more LA (n = 577, 94%) in crisis compared to post-crisis periods (n = 179, 57%) (p < 0.001). Discussion Our study suggests that populations at risk for humanitarian crises are still vulnerable to traumatic LA. Appropriate operative and post-operative LA management in the humanitarian setting must be provided, including rehabilitation and options for prosthetic devices.
  • Seizure activity and anion gap metabolic acidosis secondary to adverse effect of nalidixic acid—a case report

    Galvin, M; Al Qaisy, MS; Cajazeiro, J (Oxford University Press, 2021-01-12)
    Nalidixic acid is a commonly prescribed treatment for suspected dysentery in Middle Eastern populations. We describe a case of convulsions resulting from a single dose of nalidixic acid in a previously healthy two-month-old child in Northern Iraq who was being treated for a diarrhoeal illness. The child presented to us with new onset seizures, irritability, and acidaemia. Nalidixic acid was thought to be responsible after the exclusion of other potential causes of seizures. Symptoms resolved by treatment with intravenous (IV) diazepam, and cessation of nalidixic acid, and the child recovered fully and was discharged home neurologically intact after two days of observation. In regions where it is commonly prescribed, such as Northern Iraq, nalidixic acid should be considered as a cause of convulsions in any seizing child who has been exposed to the drug. Furthermore, quinolones such as nalidixic acid are contraindicated in children < 3 months of age.
  • Clinical outcomes in a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: A cohort analysis using routine data

    Ansbro, E; Homan, T; Prieto Merino, D; Jobanputra, K; Qasem, J; Muhammad, S; Fardous, T; Perel, P (Public Library of Science, 2021-01-11)
    Background Little is known about the content or quality of non-communicable disease (NCD) care in humanitarian settings. Since 2014, Médecins Sans Frontières (MSF) has provided primary-level NCD services in Irbid, Jordan, targeting Syrian refugees and vulnerable Jordanians who struggle to access NCD care through the overburdened national health system. This retrospective cohort study explored programme and patient-level patterns in achievement of blood pressure and glycaemic control, patterns in treatment interruption, and the factors associated with these patterns. Methods and findings The MSF multidisciplinary, primary-level NCD programme provided facility-based care for cardiovascular disease, diabetes, and chronic respiratory disease using context-adapted guidelines and generic medications. Generalist physicians managed patients with the support of family medicine specialists, nurses, health educators, pharmacists, and psychosocial and home care teams. Among the 5,045 patients enrolled between December 2014 and December 2017, 4,044 eligible adult patients were included in our analysis, of whom 72% (2,913) had hypertension and 63% (2,546) had type II diabetes. Using visits as the unit of analysis, we plotted the following on a monthly basis: mean blood pressure among hypertensive patients, mean fasting blood glucose and HbA1c among type II diabetic patients, the proportion of each group achieving control, mean days of delayed appointment attendance, and the proportion of patients experiencing a treatment interruption. Results are presented from programmatic and patient perspectives (using months since programme initiation and months since cohort entry/diagnosis, respectively). General linear mixed models explored factors associated with clinical control and with treatment interruption. Mean age was 58.5 years, and 60.1% (2,432) were women. Within the programme’s first 6 months, mean systolic blood pressure decreased by 12.4 mm Hg from 143.9 mm Hg (95% CI 140.9 to 146.9) to 131.5 mm Hg (95% CI 130.2 to 132.9) among hypertensive patients, while fasting glucose improved by 1.12 mmol/l, from 10.75 mmol/l (95% CI 10.04 to 11.47) to 9.63 mmol/l (95% CI 9.22 to 10.04), among type II diabetic patients. The probability of achieving treatment target in a visit was 63%–75% by end of 2017, improving with programme maturation but with notable seasonable variation. The probability of experiencing a treatment interruption declined as the programme matured and with patients’ length of time in the programme. Routine operational data proved useful in evaluating a humanitarian programme in a real-world setting, but were somewhat limited in terms of data quality and completeness. We used intermediate clinical outcomes proven to be strongly associated with hard clinical outcomes (such as death), since we had neither the data nor statistical power to measure hard outcomes. Conclusions Good treatment outcomes and reasonable rates of treatment interruption were achieved in a multidisciplinary, primary-level NCD programme in Jordan. Our approach to using continuous programmatic data may be a feasible way for humanitarian organisations to account for the complex and dynamic nature of interventions in unstable humanitarian settings when undertaking routine monitoring and evaluation. We suggest that frequency of patient contact could be reduced without negatively impacting patient outcomes and that season should be taken into account in analysing programme performance.
  • Immunogenicity and safety of fractional doses of yellow fever vaccines: a randomised, double-blind, non-inferiority trial

    Juan-Giner, A; Kimathi, D; Grantz, KH; Hamaluba, M; Kazooba, P; Njugana, P; Fall, G; Dia, M; Bob, NS; Monath, TP; et al. (Elsevier, 2021-01-09)
    Background Stocks of yellow fever vaccine are insufficient to cover exceptional demands for outbreak response. Fractional dosing has shown efficacy, but evidence is limited to the 17DD substrain vaccine. We assessed the immunogenicity and safety of one-fifth fractional dose compared with standard dose of four WHO-prequalified yellow fever vaccines produced from three substrains. Methods We did this randomised, double-blind, non-inferiority trial at research centres in Mbarara, Uganda, and Kilifi, Kenya. Eligible participants were aged 18–59 years, had no contraindications for vaccination, were not pregnant or lactating, had no history of yellow fever vaccination or infection, and did not require yellow fever vaccination for travel. Eligible participants were recruited from communities and randomly assigned to one of eight groups, corresponding to the four vaccines at standard or fractional dose. The vaccine was administered subcutaneously by nurses who were not masked to treatment, but participants and other study personnel were masked to vaccine allocation. The primary outcome was proportion of participants with seroconversion 28 days after vaccination. Seroconversion was defined as post-vaccination neutralising antibody titres at least 4 times pre-vaccination measurement measured by 50% plaque reduction neutralisation test (PRNT50). We defined non-inferiority as less than 10% decrease in seroconversion in fractional compared with standard dose groups 28 days after vaccination. The primary outcome was measured in the per-protocol population, and safety analyses included all vaccinated participants. This trial is registered with, NCT02991495. Findings Between Nov 6, 2017, and Feb 21, 2018, 1029 participants were assessed for inclusion. 69 people were ineligible, and 960 participants were enrolled and randomly assigned to vaccine manufacturer and dose (120 to Bio-Manguinhos-Fiocruz standard dose, 120 to Bio-Manguinhos-Fiocruz fractional dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides standard dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides fractional dose, 120 to Institut Pasteur Dakar standard dose, 120 to Institut Pasteur Dakar fractional dose, 120 to Sanofi Pasteur standard dose, and 120 to Sanofi Pasteur fractional dose). 49 participants had detectable PRNT50 at baseline and 11 had missing PRNT50 results at baseline or 28 days. 900 were included in the per-protocol analysis. 959 participants were included in the safety analysis. The absolute difference in seroconversion between fractional and standard doses by vaccine was 1·71% (95% CI −2·60 to 5·28) for Bio-Manguinhos-Fiocruz, −0·90% (–4·24 to 3·13) for Chumakov Institute of Poliomyelitis and Viral Encephalitides, 1·82% (–2·75 to 5·39) for Institut Pasteur Dakar, and 0·0% (–3·32 to 3·29) for Sanofi Pasteur. Fractional doses from all four vaccines met the non-inferiority criterion. The most common treatment-related adverse events were headache (22·2%), fatigue (13·7%), myalgia (13·3%) and self-reported fever (9·0%). There were no study-vaccine related serious adverse events. Interpretation Fractional doses of all WHO-prequalified yellow fever vaccines were non-inferior to the standard dose in inducing seroconversion 28 days after vaccination, with no major safety concerns. These results support the use of fractional dosage in the general adult population for outbreak response in situations of vaccine shortage.
  • Prevalence of HIV, viral hepatitis B/C and tuberculosis and treatment outcomes among people who use drugs: Results from the implementation of the first drop-in-center in Mozambique

    Sema Baltazar, C; Kellogg, TA; Boothe, M; Loarec, A; de Abreu, E; Condula, M; Fazito, E; Raymond, HF; Temmerman, M; Luchters, S (Elsevier, 2021-01-08)
    Background People who use drugs (PWUD) which includes both people who inject drugs (PWID) and non-injection drug users (NIDU) are marginalized, experience high levels of stigma and discrimination, and are likely to have challenges with accessing health services. Mozambique implemented the first drop-in center (DIC) for PWUD in Maputo City in 2018. This analysis aims to assess the prevalence of HIV, viral hepatitis B (HBV) and C (HCV) and tuberculosis (TB) among PWUD, and assess their linkage to care and associated correlates. Methods We conducted a cross-sectional retrospective analysis of routine screening data collected from the first visit at the drop-in center (DIC) during the period of May 2018 to November 2019 (18 months). Descriptive and multivariable logistic regression analysis were conducted to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) of HIV, HBV, HCV and TB infections among PWID and NIDU. Cox proportional hazards models of determinants were used to estimate time from HIV diagnosis to linkage to care for PWUD. Results A total of 1,818 PWUD were screened at the DIC, of whom 92.6% were male. The median age was 27 years (range:14–63). Heroin was the most consumed drug (93.8%), and among people who used it, 15.5% injected it. Prevalence of HIV (43.9%), HCV (22.6%) and HBV (5.9%) was higher among PWID (p<0.001). Linkage to HIV care was observed in 40.5% of newly diagnosed PWID. Factors associated with shorter time to linkage to care included drug injection (aHR=1.6) and confirmed TB infection (aHR=2.9). Conclusion This was the first analysis conducted on the implementation of the DIC in Mozambique and highlights the importance of targeted services for this high-risk population. Our analysis confirmed a high prevalence of HIV, HBV and HCV, and highlight the challenges with linkage to care among PWID. The expansion of DIC locations to other high-risk localities to enhance HIV testing, treatment services and linkage to care to reduce ongoing transmission of HIV, HBV, HCV and TB and improve health outcomes.
  • Resilience to maintain quality of intrapartum care in war torn Yemen: a retrospective pre-post study evaluating effects of changing birth volumes in a congested frontline hospital

    Obel, J; Martin, AIC; Mullahzada, AW; Kremer, R; Maaloe, N (BMC, 2021-01-07)
    Background Fragile and conflict-affected states contribute with more than 60% of the global burden of maternal mortality. There is an alarming need for research exploring maternal health service access and quality and adaptive responses during armed conflict. Taiz Houbane Maternal and Child Health Hospital in Yemen was established during the war as such adaptive response. However, as number of births vastly exceeded the facility’s pre-dimensioned capacity, a policy was implemented to restrict admissions. We here assess the restriction’s effects on the quality of intrapartum care and birth outcomes. Methods A retrospective before and after study was conducted of all women giving birth in a high-volume month pre-restriction (August 2017; n = 1034) and a low-volume month post-restriction (November 2017; n = 436). Birth outcomes were assessed for all births (mode of birth, stillbirths, intra-facility neonatal deaths, and Apgar score < 7). Quality of intrapartum care was assessed by a criterion-based audit of all caesarean sections (n = 108 and n = 82) and of 250 randomly selected vaginal births in each month. Results Background characteristics of women were comparable between the months. Rates of labour inductions and caesarean sections increased significantly in the low-volume month (14% vs. 22% (relative risk (RR) 0.62, 95% confidence interval (CI) 0.45-0.87) and 11% vs. 19% (RR 0.55, 95% CI 0.42-0.71)). No other care or birth outcome indicators were significantly different. Structural and human resources remained constant throughout, despite differences in patient volume. Conclusions Assumptions regarding quality of care in periods of high demand may be misguiding - resilience to maintain quality of care was strong. We recommend health actors to closely monitor changes in quality of care when implementing resource changes; to enable safe care during birth for as many women as possible.
  • Accuracy of molecular drug susceptibility testing amongst tuberculosis patients in Karakalpakstan, Uzbekistan.

    Gil, Horacio; Margaryan, Hasmik; Azamat, Ismailov; Ziba, Bekturdieva; Bayram, Halmuratov; Nazirov, Pirimqul; Gomez, Diana; Singh, Jatinder; Zayniddin, Sayfutdinov; Parpieva, Nargiza; et al. (2021-01-06)
    Objectives In this retrospective study, we evaluated the diagnostic accuracy of molecular tests (MT) for the detection of DR‐TB, compared to the gold standard liquid‐based Drug Susceptibility Testing (DST) in Karakalpakstan. Methods A total of 6,670 specimens received in the Republican TB No 1 Hospital Laboratory of Karakalpakstan between January and July 2017 from new and retreatment patients were analyzed. Samples were tested using Xpert MTB/RIF and line probe assays (LPA) for the detection of mutations associated with resistance. The sensitivity and specificity of MTs were calculated relative to results based on DST. Results The accuracy of MT for detection of rifampicin resistance was high, with sensitivity and specificity over 98%. However, we observed reduced sensitivity of LPA for detection of resistance; 86% for isoniazid (95%CI 82‐90%), 86% for fluoroquinolones (95%CI 68‐96%), 70% for capreomycin (95%CI 46‐88%) and 23% for kanamycin (95%CI 13‐35%). Conclusions We show that MTs are a useful tool for rapid and safe diagnosis of DR‐TB, however, clinicians should be aware of their limitations. Although detection of rifampicin resistance was highly accurate, our data suggests that resistance mutations circulating in the Republic of Karakalpakstan for other drugs were not detected by the methods used here. This merits further investigation.
  • Accuracy of molecular drug susceptibility testing amongst tuberculosis patients in Karakalpakstan, Uzbekistan

    Gil, H; Margaryan, H; Azamat, I; Ziba, B; Bayram, H; Nazirov, P; Gomez, D; Singh, J; Zayniddin, S; Parpieva, N; et al. (Wiley, 2021-01-06)
    Objectives In this retrospective study, we evaluated the diagnostic accuracy of molecular tests (MT) for the detection of DR‐TB, compared to the gold standard liquid‐based drug susceptibility testing (DST) in Karakalpakstan. Methods A total of 6670 specimens received in the Republican TB No 1 Hospital Laboratory of Karakalpakstan between January and July 2017 from new and retreatment patients were analysed. Samples were tested using Xpert MTB/RIF and line probe assays (LPA) for the detection of mutations associated with resistance. The sensitivity and specificity of MTs were calculated relative to results based on DST. Results The accuracy of MT for detection of rifampicin resistance was high, with sensitivity and specificity over 98%. However, we observed reduced sensitivity of LPA for detection of resistance; 86% for isoniazid (95% CI 82–90%), 86% for fluoroquinolones (95% CI 68‐96%), 70% for capreomycin (95% CI 46–88%) and 23% for kanamycin (95% CI 13–35%). Conclusions We show that MTs are a useful tool for rapid and safe diagnosis of DR‐TB; however, clinicians should be aware of their limitations. Although detection of rifampicin resistance was highly accurate, our data suggest that resistance mutations circulating in the Republic of Karakalpakstan for other drugs were not detected by the methods used here. This merits further investigation.
  • Ending deaths from HIV-related cryptococcal meningitis by 2030

    Shroufi, A; Chiller, T; Jordan, A; Denning, DW; Harrison, TS; Govender, NP; Loyse, A; Baptiste, S; Rajasingham, R; Boulware, DR; et al. (Elsevier, 2021-01-01)
    The UNAIDS target to reduce HIV-related death to fewer than 500 000 deaths per year by 2020 will not be met. 1 This statement might not be headline grabbing as this target was never as prominent as the 90-90-90 targets, 2 the achievement of which is a necessary but not sufficient step towards ending AIDS mortality.
  • Safety and effectiveness of an all-oral, bedaquiline-based, shorter treatment regimen for rifampicin-resistant tuberculosis in high HIV burden rural South Africa: a retrospective cohort analysis

    Tack, I; Dumicho, A; Ohler, L; Shigayeva, A; Bulti, AB; White, K; Mbatha, M; Furin, J; Isaakidis, P (Oxford University Press, 2020-12-29)
    Background At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and two months of linezolid (LZD) for all patients initiating the shorter 9 to 12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. Methods We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between July 1, 2018 and April 30, 2019 in three facilities in King Cetshwayo District. An electronic register (EDR Web) and facility-based clinical charts were used to collect variables which were entered into an Epi-Info database. Results Our cohort included 117 patients; 68.4%(95%CI:59.3-76.3) were HIV positive. The median time to culture conversion was 56 days(95%CI:50-57). Treatment success was achieved in 75.2%(95%CI:66.5-82.3) of patients. Mortality within the cohort was 12.8%(95%CI:7.8-20.3). Anaemia was the most frequent severe adverse event. The median time to develop severe anaemia was 7.1 weeks(IQR 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2%(95%CI:17.8-34.5) of participants. Conclusions An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. Adverse events (AEs) are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to upskill staff in the monitoring, management and reporting of AEs.
  • Evaluation of community based surveillance in the Rohingya refugee camps in Cox’s Bazar, Bangladesh, 2019

    Van Boetzelaer, E; Chowdhury, S; Etsay, B; Faruque, A; Lenglet, A; Kuehne, A; Carrion-Martin, I; Keating, P; Dada, M; Vyncke, J; et al. (Public Library of Sciences, 2020-12-23)
    Background Following an influx of an estimated 742,000 Rohingya refugees in Bangladesh, Médecins sans Frontières (MSF) established an active indicator-based Community Based Surveillance (CBS) in 13 sub-camps in Cox’s Bazar in August 2017. Its objective was to detect epidemic prone diseases early for rapid response. We describe the surveillance, alert and response in place from epidemiological week 20 (12 May 2019) until 44 (2 November 2019). Methods Suspected cases were identified through passive health facility surveillance and active indicator-based CBS. CBS-teams conducted active case finding for suspected cases of acute watery diarrhea (AWD), acute jaundice syndrome (AJS), acute flaccid paralysis (AFP), dengue, diphtheria, measles and meningitis. We evaluate the following surveillance system attributes: usefulness, Positive Predictive Value (PPV), timeliness, simplicity, flexibility, acceptability, representativeness and stability. Results Between epidemiological weeks 20 and 44, an average of 97,340 households were included in the CBS per surveillance cycle. Household coverage reached over 85%. Twenty-one RDT positive cholera cases and two clusters of AWD were identified by the CBS and health facility surveillance that triggered the response mechanism within 12 hours. The PPV of the CBS varied per disease between 41.7%-100%. The CBS required 354 full-time staff in 10 different roles. The CBS was sufficiently flexible to integrate dengue surveillance. The CBS was representative of the population in the catchment area due to its exhaustive character and high household coverage. All households consented to CBS participation, showing acceptability. Discussion The CBS allowed for timely response but was resource intensive. Disease trends identified by the health facility surveillance and suspected diseases trends identified by CBS were similar, which might indicate limited additional value of the CBS in a dense and stable setting such as Cox’s Bazar. Instead, a passive community-event-based surveillance mechanism combined with health facility-based surveillance could be more appropriate.
  • Impact of food supplements on early child development in children with moderate acute malnutrition: A randomised 2 x 2 x 3 factorial trial in Burkina Faso

    Olsen, MF; Iuel-Brockdorff, AS; Yameogo, CW; Cichon, B; Fabiansen, C; Filteau, S; Phelan, K; Ouedraogo, A; Michaelsen, KF; Gladstone, M; et al. (Public Library of Science, 2020-12-23)
    Background Lipid-based nutrient supplements (LNS) and corn–soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. Methods and findings We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks’ supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6–23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2–16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [−0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (−0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. Conclusions In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation.
  • Urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards identifies a large proportion of patients with tuberculosis at risk of death

    Huerga, H; Mathabire Rucker, SC; Bastard, M; Mpunga, J; Amoros Quiles, I; Kabaghe, C; Sannino, L; Szumilin, E (Oxford University Press, 2020-12-23)
    Background Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards and 6-month mortality according to the LAM result. Methods This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest X-ray, and CD4 count were systematically requested. Results Among 387 inpatients, 54% had a CD4<200 cells/µL, 64% had presumptive TB and 90% had ≥1 TB symptom recorded in the medical file. LAM results were available for 99.0% of the patients, microscopy for 62.8% and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-months mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives, p=0.013. In multivariable regression analyses, LAM-positive patients had higher risk of mortality than LAM-negatives (aOR: 2.5, 95%CI: 1.1-5.8, p=0.037). Conclusions In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine-LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.
  • hlers

    Mashe, T; Leekitcharoenphon, P; Mtapuri-Zinyowera, S; Kingsley, RA; Robertson, V; Tarupiwa, A; Kock, MM; Makombe, EP; Chaibva, BV; Manangazira, P; et al. (Oxford University Press, 2020-12-21)
    Background Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control. Objectives To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics. Methods : A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis. Results A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (, with a maximum pair-wise distance of 22 SNPs. Conclusions This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.
  • Twenty‐four‐month outcomes from a cluster‐randomized controlled trial of extending antiretroviral therapy refills in ART adherence clubs

    Cassidy, T; Grimsrud, A; Keene, C; Lebelo, K; Hayes, H; Orrell, C; Zokufa, N; Mutsetekwa, T; Voget, J; Gerstenhaber, R; et al. (Wiley Open Access, 2020-12-19)
    Introduction The antiretroviral therapy (ART) adherence club (AC) model has supported clinically stable HIV patients’ retention with group ART refills and psychosocial support. Reducing visit frequency by increasing ART refills to six months could further benefit patients and unburden health systems. We conducted a pragmatic non‐inferiority cluster randomized trial comparing standard of care (SoC) ACs and six‐month refill intervention ACs in a primary care facility in Khayelitsha, South Africa. Methods Existing community‐based and facility‐based ACs were randomized to either SoC or intervention ACs. SoC ACs met five times annually, receiving two‐month refills with a four‐month refill over year‐end. Blood was drawn at one AC visit with a clinical assessment at the next. Intervention ACs met twice annually receiving six‐month refills, with an individual blood collection visit before the annual clinical assessment AC visit. The first study visits were in October and November 2017 and participants followed for 27 months. We report retention in care, viral load completion and viral suppression (<400 copies/mL) 24 months after enrolment and calculated intention‐to‐treat risk differences for the primary outcomes using generalized estimating equations specifying for clustering by AC. Results Of 2150 participants included in the trial, 977 were assigned to the intervention arm (40 ACs) and 1173 to the SoC (48 ACs). Patient characteristics at enrolment were similar across groups. Retention in care at 24 months was similarly high in both arms: 93.6% (1098/1173) in SoC and 92.6% (905/977) in the intervention arm, with a risk difference of −1.0% (95% CI: −3.2 to 1.3). The intervention arm had higher viral load completion (90.8% (999/1173) versus 85.1% (887/977)) and suppression (87.3% (969 /1173) versus 82.6% (853/977)) at 24 months, with a risk difference for completion of 5.5% (95% CI: 1.5 to 9.5) and suppression of 4.6% (95% CI: 0.2 to 9.0). Conclusions Intervention AC patients receiving six‐month ART refills showed non‐inferior retention in care, viral load completion and viral load suppression to those in SoC ACs, adding to a growing literature showing good outcomes with extended ART dispensing intervals.
  • Association of prevalence of active transport to work and incidence of myocardial infarction: A nationwide ecological study

    Munyombwe, T; Lovelace, R; Green, M; Norman, P; Walpole, S; Hall, M; Timmis, A; Batin, P; Brownlee, A; Brownlee, J; et al. (SAGE Publications, 2020-12-18)
    Background There is a paucity of population-based geospatial data about the association between active transport and myocardial infarction. We investigated the association between active transport to work and incidence of myocardial infarction. Design This ecological study of 325 local authorities in England included 43,077,039 employed individuals aged 25–74 years (UK Census, 2011), and 117,521 individuals with myocardial infarction (Myocardial Ischaemia National Audit Project, 2011–2013). Methods Bayesian negative binomial regression models were used to investigate the association of active transport to work and incidence of myocardial infarction adjusting for local levels of deprivation, obesity, smoking, diabetes and physical activity. Results In 2011, the prevalence of active transportation to work for people in employment in England aged 25–74 years was 11.4% (4,531,182 active transporters; 8.6% walking and 2.8% cycling). Active transport in 2011 was associated with a reduced incidence of myocardial infarction in 2012 amongst men cycling to work (incidence rate ratio (95% credible interval) 0.983 (0.967–0.999); and women walking to work (0.983 (0.967–0.999)) after full adjustments. However, the prevalence of active transport for men and women was not significantly associated with the combined incidence of myocardial infarction between 2011–2013 after adjusting for physical activity, smoking and diabetes. Conclusions In England, the prevalence of active transportation was associated with a reduced incidence of myocardial infarction for women walking and men cycling to work in corresponding local geographic areas. The overall association of active transport with myocardial infarction was, however, explained by local area levels of smoking, diabetes and physical activity.

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