Now showing items 41-60 of 3144

    • Organophosphate poisoning in a young child: a case report

      Sharma, N; Nin-Gonzalez, R (Oxford University Press, 2021-02-02)
      Unintentional ingestions are a common form of poisoning in children worldwide. Organophosphates are commonly used in households worldwide and are a common cause of childhood poisonings. This case report describes an unintentional ingestion of a child in East Africa. A thorough patient history and a high index of suspicion are needed in recognizing an organophosphate poisoning. Prompt patient stabilization and treatment improve outcomes. Neurologic sequela may occur and thus patient follow-up is recommended.
    • Cost and cost-effectiveness of a real-world HCV treatment program among HIV-infected individuals in Myanmar.

      Marquez, LK; Chaillon, A; Soe, KP; Johnson, DC; Zosso, JM; Incerti, A; Loarec, A; Nguyen, A; Walker, JG; Mafirakureva, N; et al. (BMJ Publishing Group, 2021-02-01)
      Introduction: Over half of those hepatitis C virus (HCV)/HIV coinfected live in low-income and middle-income countries, and many remain undiagnosed or untreated. In 2016, Médecins Sans Frontières (MSF) established a direct-acting antiviral (DAA) treatment programme for people HCV/HIV coinfected in Myanmar. The purpose of our study was to evaluate the real-world cost and cost-effectiveness of this programme, and potential cost-effectiveness if implemented by the Ministry of Health (MoH). Methods: Costs (patient-level microcosting) and treatment outcomes were collected from the MSF prospective cohort study in Dawei, Myanmar. A Markov model was used to assess cost-effectiveness of the programme compared with no HCV treatment from a health provider perspective. Estimated lifetime and healthcare costs (in 2017 US$) and health outcomes (in disability-adjusted life-years (DALYs)) were simulated to calculate the incremental cost-effectiveness ratio (ICER), compared with a willingness-to-pay threshold of per capita Gross Domestic Product in Myanmar ($1250). We evaluated cost-effectiveness with updated quality-assured generic DAA prices and potential cost-effectiveness of a proposed simplified treatment protocol with updated DAA prices if implemented by the MoH. Results: From November 2016 to October 2017, 122 with HIV/HCV-coinfected patients were treated with DAAs (46% with cirrhosis), 96% (n=117) achieved sustained virological response. Mean treatment costs were $1229 (without cirrhosis) and $1971 (with cirrhosis), with DAA drugs being the largest contributor to cost. Compared with no treatment, the program was cost-effective (ICER $634/DALY averted); more so with updated prices for quality-assured generic DAAs (ICER $488/DALY averted). A simplified treatment protocol delivered by the MoH could be cost-effective if associated with similar outcomes (ICER $316/DALY averted). Conclusions: Using MSF programme data, the DAA treatment programme for HCV among HIV-coinfected individuals is cost-effective in Myanmar, and even more so with updated DAA prices. A simplified treatment protocol could enhance cost-effectiveness if further rollout demonstrates it is not associated with worse treatment outcomes.
    • Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy-A retrospective analysis.

      Kamink, S; Masih, B; Ali, N; Ullah, A; Khan, SJ; Ashraf, S; Pylypenko, T; Grobusch, MP; Fernhout, J; den Boer, M; et al. (Public Library of Science, 2021-01-28)
      Background: Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by Leishmania protozoa. In Pakistan, where CL caused by L. tropica is highly endemic, therapy with pentavalent antimonials is the standard of care, but has significant toxicity when used in systemic therapy, while are no evidence-based safer alternative treatment options for L. tropica. The efficacy of oral miltefosine has not been studied in CL caused by L. tropica. We evaluated effectiveness and tolerability of miltefosine in patients with previous treatment failure or with contraindications to systemic antimonial treatment. Methods: A retrospective review was conducted of a cohort of CL patients who were treated with a 28-day course of miltefosine between December 2017 and August 2019, in urban Quetta, Pakistan, an area endemic for L. tropica. Descriptive analyses were performed, and effectiveness was assessed by initial response after treatment, and final cure at routine follow up visits, six weeks to three months post-treatment. Tolerability was assessed by routinely reported adverse events. Results: Of the 76 CL patients in the cohort, 42 (55%) had contraindications to systemic antimonial treatment, and 34 (45%) had failure or relapse after antimonial treatment. Twelve patients defaulted during treatment and 12 patients were lost to follow up. In the remaining 52 patients, final cure rate was 77% (40/52). In those with contraindications to systemic antimonial treatment the final cure rate was 83% (24/29) and in the failure and relapse group 70% (16/23). Twenty-eight patients (40.0%) reported 39 mild to moderate adverse events with the main complaints being nausea (41.0%), general malaise (25.6%), and stomach pain (12.8%). Conclusion: Results indicate that miltefosine is an effective second line treatment in CL in areas endemic for L. tropica. Prospective studies with systematic follow up are needed to obtain definitive evidence of effectiveness and tolerability, including identification of risk factors for miltefosine treatment failure.
    • Description of a community paediatric strategy offering a package of services to prevent malnutrition among children in one health district in Mali

      Roederer, T; Llosa, AE; Shepherd, S; Defourny, I; Lacharite, MO; Okonta, C; Magassa, M; Traore, M; Schaefer, M; Grais, RF (2021-01-26)
      Background We present results from an intervention case study, the Soins Preventifs de l’Enfant (SPE) project, in Konséguéla health area, Mali. The intervention involved a network of community health workers providing a comprehensive preventive/therapeutic package, ultimately aiming at reducing under 24-month mortality. Associated costs were documented to assess the feasibility of replication and scale-up. Methods SPE program monitoring data were obtained from booklets specific to the program between 2010 and 2014. Data included sex, age, vaccination status, anthropometric measurements, Ready-To-Use-Supplementary Food distribution, morbidities reported by the mother between visits, hospitalizations over 18 months of follow-up. Cross-sectional surveys in the district of Koutiala, of which Konséguéla is one health area, were conducted yearly between 2010 and 2014 for comparison, using difference-in-difference approach. Ethical approval was granted from the Malian Ethical Committee. Results Global and Severe Acute Malnutrition prevalences decreased over time in Konséguéla as well as in the rest of the district, but the difference between areas was not significant. Children reaching 24 months were 20% less stunted in Konséguéla than children the same age outside (p<0.001). Mortality rates significantly decreased more in Konséguéla, while vaccination coverage for all antigens significantly increased in the meantime. The package cost approximately USD 95 per child per year; 56% of which was for the RUSF. Conclusion The results of this case study suggest a sustained impact of a community based, comprehensive health package on major child health indicators. Most notably, while improvements in acute malnutrition were found in the district as a whole, those in the intervention area were more pronounced. Trends for other indicators suggest additional benefits.
    • Prediction of disease severity in young children presenting with acute febrile illness in resource-limited settings: a protocol for a prospective observational study.

      Chandna, A; Aderie, EM; Ahmad, R; Arguni, E; Ashley, EA; Cope, T; Dat, VQ; Day, NPJ; Dondorp, AM; Illanes, V; et al. (BMJ Publishing Group, 2021-01-25)
      Introduction: In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care. Methods and analysis: This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies. Ethics and dissemination: The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings.
    • 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.
    • The political and security dimensions of the humanitarian health response to violent conflict.

      Wise, PH; Shiel, A; Southard, N; Bendavid, E; Welsh, J; Stedman, S; Fazal, T; Felbab-Brown, V; Polatty, D; Waldman, RJ; et al. (Elsevier, 2021-01-24)
      The nature of armed conflict throughout the world is intensely dynamic. Consequently, the protection of non-combatants and the provision of humanitarian services must continually adapt to this changing conflict environment. Complex political affiliations, the systematic use of explosive weapons and sexual violence, and the use of new communication technology, including social media, have created new challenges for humanitarian actors in negotiating access to affected populations and security for their own personnel. The nature of combatants has also evolved as armed, non-state actors might have varying motivations, use different forms of violence, and engage in a variety of criminal activities to generate requisite funds. New health threats, such as the COVID-19 pandemic, and new capabilities, such as modern trauma care, have also created new challenges and opportunities for humanitarian health provision. In response, humanitarian policies and practices must develop negotiation and safety capabilities, informed by political and security realities on the ground, and guidance from affected communities. More fundamentally, humanitarian policies will need to confront a changing geopolitical environment, in which traditional humanitarian norms and protections might encounter wavering support in the years to come.
    • Virologic response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10-14 years) in South Africa.

      Nyakato, P; Schomaker, M; Sipambo, N; Technau, KG; Fatti, G; Rabie, H; Tanser, F; Eley, B; Euvrard, J; Wood, R; et al. (Lippincott, Williams & Wilkins, 2021-01-21)
      Background and objectives: Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with nonperinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence. Design: A retrospective cohort study Methods: We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004–2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs. Results: We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a nonnucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex. Conclusions: As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.
    • Delivery strategies for optimizing uptake of contraceptives among adolescents aged 15-19 years in Nsanje District, Malawi.

      Makinja, AK; Maida, ZM; Nyondo-Mipando, AL (BMC, 2021-01-20)
      Background Despite documented benefits of contraceptives, uptake among young people aged 20–24 years is high compared to adolescents aged 15–19 years in Malawi. As the world’s population of 15–19-year-olds continues to grow the need to meet the increasing demand for contraceptive services and information that address adolescent-specific needs cannot be underestimated. To inform Sexual and Reproductive health services for the youth, we explored strategies for optimizing uptake of contraceptives among this age group. Methods An exploratory qualitative cross-sectional study was conducted at Nsanje District Hospital and Nyamadzere Community Day Secondary School guided by Social-Ecological Framework to understand strategies that may optimize the uptake of contraceptives among adolescents aged 15–19. Nsanje district was purposively selected based on the reason that it is the second district in Malawi with the highest rate of adolescent childbearing of girls aged 15–19 years. We conducted a Focus Group Discussion (FGD) with 9 traditional leaders, 11 Key Informant Interviews (KIIs) with health workers, 20 In-depth Interviews (IDIs) with 12 adolescents, 4 teachers, and 4 parents. All data were digitally recorded, transcribed verbatim into English. The data was analyzed and managed using deductive thematic analysis guided by Social-Ecological Framework. Results Adolescents suggested accessing contraceptives from local drug stores, pharmacies and hospitals at a health system level and through Youth Centres, clubs, and corners at a Community level. There is a need to ensure a continuous supply of various kinds of contraceptives and the presence of youth-friendly health care workers in the specified areas. Conclusion There is no one way of delivering contraceptives to adolescents. Multiple avenues existent at the health facility and community could be leveraged to optimize delivery and uptake of contraceptives in a manner that is not intimidating to an adolescent while involving key stakeholders.
    • 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.
    • Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin

      Coldiron, ME; Gutierrez Zamudio, AG; Manuel, R; Luciano, G; Rusch, B; Ciglenecki, I; Telnov, A; Grais, RF; Trellu, LT; Molfino, L (BMC, 2021-01-07)
      Background Kaposi’s sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique. Methods We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment. Results At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2–6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1–6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD. Discussion PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.
    • 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.
    • 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.
    • 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.