Department For International Development Research Articles

Household Air Pollution (HAP) is Associated With Increased Pneumococcal Carriage in Malawian Infants – Malawi  <i>Streptococcus pneumoniae</i> Carriage and Air Pollution Exposure (MSCAPE) Study

Background: Household air pollution (HAP) from solid cooking fuels is a risk factor for childhood pneumonia. Nasopharyngeal carriage of Streptococcus pneumoniae is a necessary step in development of pneumococcal pneumonia. We hypothesised that HAP influences S. pneumoniae carriage. MSCAPE assesses the relationship between HAP from solid cooking fuels and prevalence/density of S. pneumoniae carriage among children. Methods: MSCAPE is a prospective study of children participating in a trial of a cleaner burning cookstove to reduce childhood pneumonia incidence in Malawi (CAPS). MSCAPE assessed the impact of HAP exposure on prevalence of S. pneumoniae carriage in 6 week and 6 month old children through intention-to-treat and adjusted exposure-response analyses. Exposure to HAP (PM2·5) was assessed through RTI Micropem and S. pneumoniae detection in nasopharyngeal swabs. Findings: S. pneumoniae carriage prevalence was 39% (n=89) and 85% (n=398) in 6 week and 6 month old children respectively. A higher mean PM2·5 exposure was observed in intervention children (53·9 µg/m3) than controls (49·0 µg/m3), although not significant (p>0.05). Intention-to-treat analysis found a non-significant increased risk of S. pneumoniae carriage in intervention children (OR=1·36; 95% CI:0·97, 1·92). Exposure-response analysis found a significant association between HAP exposure and S. pneumoniae carriage with a 10% increase in risk per decile of PM2·5 exposure (OR=1·10; 95% CI:1·01, 1·20, p=0·035). Interpretation: Despite the lack of observed impact from the cleaner burning cookstove intervention, HAP exposure (PM 2·5) was significantly associated with S. pneumoniae prevalence giving empirical evidence for the potential mechanistic relationship between HAP and childhood pneumonia. Funding Statement: This work was supported by Bill and Melinda Gates Foundation through grant number OPP1131425. The CAPS was funded by a Joint Global Health Trials Grant from the Medical Research Council, the UK Department for International Development and Wellcome Trust (MR/K006533/1). Declaration of Interests: There are no financial competing interests in relation to the work described. Ethics Approval Statement: Ethical approval was provided by the College of Medicine Research and Ethics Committee (COMREC), Malawi (P.08/15/1794) and the Central Ethics Committee of the University of Liverpool (RETH000839).

Associations Between Biomarkers of Environmental Enteric Dysfunction and Oral Rotavirus Vaccine Immunogenicity in Rural Zimbabwean Infants

Abstract Background Oral rotavirus vaccines (RVV) are poorly immunogenic in low-income countries. Environmental enteric dysfunction (EED) resulting from poor water, sanitation and hygiene (WASH) may contribute. We therefore tested associations between EED and RVV immunogenicity, and evaluated the effect of improved WASH on EED. Methods We measured nine biomarkers of EED among Zimbabwean infants born to mothers enrolled in a cluster-randomised 2 × 2 factorial trial of improved WASH and improved feeding between November 2012 and March 2015 (NCT01824940). We used multivariable regression to determine associations between EED biomarkers and RVV seroconversion, seropositivity and geometric mean titer. Log-binomial regression was used to evaluate the effect of improved WASH on EED. Findings Among 303 infants with EED biomarkers and immunogenicity data, plasma intestinal fatty-acid binding protein and stool myeloperoxidase were positively associated with RVV seroconversion; adjusted RR 1.63 (95%CI 1.04, 2.57) and 1.29 (95%CI 1.01, 1.65), respectively. There were no other associations between RVV immunogenicity and either individual biomarkers or EED domains (intestinal permeability, intestinal damage, intestinal inflammation and microbial translocation). EED biomarkers did not differ between randomised WASH and non-WASH groups. Interpretation We found no evidence that EED was associated with poor RVV immunogenicity. Contrary to our hypothesis, there was weak evidence that EED was associated with increased seroconversion. EED biomarkers were not affected by a package of household-level WASH interventions. Funding This work was supported by the Wellcome Trust. The SHINE trial was funded by the Bill & Melinda Gates Foundation; UK Department for International Development (UK Aid); Swiss Agency for Developmentand Cooperation and US National Institutes of Health.

Immunogenicity and safety of fractional doses of yellow fever vaccines: a randomised, double-blind, non-inferiority trial

SummaryBackgroundStocks 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.MethodsWe 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 ClinicalTrials.gov, NCT02991495.FindingsBetween 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.InterpretationFractional 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.FundingThe study was funded by Médecins Sans Frontières Foundation, Wellcome Trust (grant no. 092654), and the UK Department for International Development. Vaccines were donated in kind.

Effectiveness of a task-sharing collaborative care model for identification and management of depressive symptoms in patients with hypertension attending public sector primary care clinics in South Africa: pragmatic parallel cluster randomised controlled trial.

BackgroundWe tested the real-world effectiveness of a collaborative task-sharing model on depressive symptom reduction in hypertensive Primary Health Care (PHC) patients in South Africa. MethodA pragmatic parallel cluster randomised trial in 20 clinics in the Dr Kenneth Kaunda district, North West province. PHC clinics were stratified by sub-district and randomised in a 1:1 ratio. Control clinics received care as usual (CAU), involving referral to PHC doctors and/or mental health specialists. Intervention clinics received CAU plus enhanced mental health training and a lay counselling referral service. Participant inclusion criteria were ≥ 18 years old, Patient Health Questionnaire-9 (PHQ-9) score ≥ 9 and receiving hypertension medication. Primary superiority outcome was ≥ 50% reduction in PHQ-9 score at 6 months. Statistical analyses comprised mixed effects regression models and a non-inferiority analysis. Trial registration number: NCT 02425124. ResultsBetween April 2015 and October 2015, 1043 participants were enrolled (504 intervention and 539 control); 82% were women; half were ≥ 55 years. At 6 and 12 months follow-up, 91% and 89% of participants were interviewed respectively. One control group participant committed suicide. There was no significant difference in the primary outcome between intervention (N=256/456) and control (N=232/492) groups (55.9% versus 50.9%; adjusted risk difference = -0.04 ([95% CI = -0.19; 0.11], p = 0.6). The difference in PHQ-9 scores was within the defined equivalence limits at 6 and 12 months for the non-inferiority analysis. LimitationsThe trial was limited by low exposure to depression treatment by trial participants and by observed co-intervention in control clinics ConclusionsIncorporating lay counselling services within collaborative care models does not produce superior nor inferior outcomes to models with specialist only counselling services. FundingThis work was supported by the UK Department for International Development [201446] as well as the National Institute of Mental Health, United States of America, grant number 1R01MH100470-01. Graham Thornicroft is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) South London at King's College London and King's College Hospital NHS Foundation Trust.

People as security risks: the framing of migration in the UK security-development nexus

ABSTRACT The migration of people across international borders has long been an area of concern for the UK and was a key issue in the public debate surrounding Brexit. This paper examines this preoccupation with the movement of people in the context of the coordination of security and development in UK government policy. The UK responded to the migration crisis of 2015 by announcing the diversion of significant development funding to prevent the movement of people. This paper examines the UK development policy discourse of the past 2 decades through an analysis of key policy documents from the UK’s Department for International Development (DfID) and traces the changing ways in which the issue of migration has been framed in DfID’s policy. It argues that in UK development policy, whereas migration used to be discussed in terms of how it impacts on poorer countries, migration is now framed as a risk to UK national security. Development aid is now framed as a solution to the problem of migration. This paper argues that this is consistent with a broader shift in the merging of security and development in UK policy where development aid is expected to address potential risks to UK national security.

Kingdom of Lesotho

In response to a request from the authorities and as part of the United Kingdom’s Department for International Development (DFID) Enhanced Data Dissemination Initiative (EDDI) 2 project, a government finance statistics (GFS) mission visited Maseru, Lesotho, during January 20–31, 2020. The mission was the last, in a series of five consecutive technical assistance (TA) missions to Lesotho, as part of the EDDI 2 project. The objective of the five-year project, that started in 2015 was to foster compilation and dissemination of GFS and public sector debt statistics (PSDS) consistent with international methodological standards. The work program under the project identified the enhancement of classification of transactions in fiscal accounts and the expansion of the institutional coverage of data to include all significant general government units as key milestones to achieve by the end of the project.

Cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine versus single screening and treatment for the control of malaria in pregnancy in Papua, Indonesia: a provider perspective analysis from a cluster-randomised trial

Malaria infection during pregnancy is associated with serious adverse maternal and birth outcomes. A randomised controlled trial in Papua, Indonesia, comparing the efficacy of intermittent preventive treatment with dihydroartemisinin-piperaquine with the current strategy of single screening and treatment showed that intermittent preventive treatment is a promising alternative treatment for the reduction of malaria in pregnancy. We aimed to estimate the incremental cost-effectiveness of intermittent preventive treatment with dihydroartemisinin-piperaquine compared with single screening and treatment with dihydroartemisinin-piperaquine. We did a provider perspective analysis. A decision tree model was analysed from a health provider perspective over a lifetime horizon. Model parameters were used in deterministic and probabilistic sensitivity analyses. Simulations were run in hypothetical cohorts of 1000 women who received intermittent preventive treatment or single screening and treatment. Disability-adjusted life-years (DALYs) for fetal loss or neonatal death, low birthweight, moderate or severe maternal anaemia, and clinical malaria were calculated from trial data and cost estimates in 2016 US dollars from observational studies, health facility costings and public procurement databases. The main outcome measure was the incremental cost per DALY averted. Relative to single screening and treatment, intermittent preventive treatment resulted in an incremental cost of US$5657 (95% CI 1827 to 9448) and 107·4 incremental DALYs averted (-719·7 to 904·1) per 1000 women; the average incremental cost-effectiveness ratio was $53 per DALY averted. Intermittent preventive treatment with dihydroartemisinin-piperaquine offers a cost-effective alternative to single screening and treatment for the prevention of the adverse effects of malaria infection in pregnancy in the context of the moderate malaria transmission setting of Papua. The higher cost of intermittent preventive treatment was driven by monthly administration, as compared with single-administration single screening and treatment. However, acceptability and feasibility considerations will also be needed to inform decision making. Medical Research Council, Department for International Development, and Wellcome Trust.

Comparison of index-linked HIV testing for children and adolescents in health facility and community settings in Zimbabwe: findings from the interventional B-GAP study

SummaryBackgroundIndex-linked HIV testing, whereby children of individuals with HIV are targeted for testing, increases HIV yield but relies on uptake. Community-based testing might address barriers to testing access. In the Bridging the Gap in HIV testing and care for children in Zimbabwe (B-GAP) study, we investigated the uptake and yield of index-linked testing in children and the uptake of community-based vs facility-based HIV testing in Zimbabwe.MethodsB-GAP was an interventional study done in the city of Bulawayo and the province of Matabeleland South between Jan 29 and Dec 12, 2018. All HIV-positive attendees (index patients) at six urban and three rural primary health-care clinics were offered facility-based or community-based HIV testing for children (age 2–18 years) living in their households who had never been tested or had tested as HIV-negative more than 6 months ago. Community-based options involved testing in the home by either a trained lay worker with a blood-based rapid diagnostic test (used in facility-based testing), or by the child's caregiver with an oral HIV test. Among consenting individuals, the primary outcome was testing uptake in terms of the proportion of eligible children tested. Secondary outcomes were uptake of the different HIV testing methods, HIV yield (proportion of eligible children who tested positive), and HIV prevalence (proportion of HIV-positive children among those tested). Logistic regression adjusting for within-index clustering was used to investigate index patient and child characteristics associated with testing uptake, and the uptake of community-based versus facility-based testing.FindingsOverall, 2870 index patients were linked with 6062 eligible children (3115 [51·4%] girls [sex unknown in seven], median age 8 years [IQR 5–13]). Testing was accepted by index patients for 5326 (87·9%) children, and 3638 were tested with a known test outcome, giving an overall testing uptake among 6062 eligible children of 60·0%. 39 children tested positive for HIV, giving an HIV prevalence among the 3638 children of 1·1% and an HIV yield among 6062 eligible children of 0·6%. Uptake was positively associated with female sex in the index patient (adjusted odds ratio [aOR] 1·56 [95% CI 1·38–1·77], p<0·0001) and child (aOR 1·10 [1·03–1·19], p=0·0080), and negatively associated with any financial cost of travel to a clinic (aOR 0·86 [0·83–0·88], p<0·0001), increased child age (6–9 years: aOR 0·99 (0·89–1·09); 10–15 years: aOR 0·91 [0·83–1·00]; and 16–18 years: aOR 0·75 [0·66–0·85]; p=0·0001 vs 2–5 years), and unknown HIV status of the mother (aOR 0·81 [0·68–0·98], p=0·027 vs HIV-positive status). Additionally, children had increased odds of being tested if community-based testing was chosen over facility-based testing at screening (1320 [73·9%] children tested of 1787 vs 2318 [65·5%] of 3539; aOR 1·49 [1·22–1·81], p=0·0001).InterpretationThe HIV yield of index-linked testing was low compared with blanket testing approaches in similar settings. Index-linked HIV testing can improve testing uptake among children, although strategies that improve testing uptake in older children are needed. Community based testing by lay workers is a feasible strategy that can be used to improve uptake of HTS among children and adolescents.FundingUK Medical Research Council, UK Department for International Development, Wellcome Trust.

THE Application of sustainable livelihood framework for the assessment of living for rural people in Tan Phuoc District, Tien Giang Province

In this study, the approach of a sustainable livelihood framework following the guidance of the Department for International Development (DFID) is used to assess the livelihoods of people in rural areas of Tan Phuoc district, Tien Giang province. This is one of the acid sulphate soil areas of the Mekong Delta. Sustainable livelihood framework according to Department for International Development in the study will consider the assets of Tan Phuoc district people to ensure livelihoods including human capital, physical capital, financial capital, natural capital, and social capital. The results show that most of the capital for developing livelihoods of people in this area is poor (natural capital, human capital, social capital, financial capital), only physical capital is considered to meet the current development needs. They are the basis for proposing development orientations for Tan Phuoc district in the future, including socio-economic development, labor quality improvement and the number of professionally trained people. Besides, there are specific s upport policies for people and there are many sources of capital to help people access policies easily. To solve this problem, first of all, it is necessary to develop development plans of regions according to natural conditions, continue to improve the skills of local communities and provide specific support policies for livelihood activities. Attract many different sources of investment capital for the locality so that people can easily access, improve the income of local people in the future, especially need a population development strategy corresponding to the development conditions of the district. The analysis is based on aggregate collected data on the different types of livelihoods in the province, so they are of great overall value. However, this is also the basis for conducting detailed studies and investigations for further studies with the aim of having accurate information and correct assessment of the current livelihood status of each district and livelihood group.

Patterns of individual non-treatment during multiple rounds of mass drug administration for control of soil-transmitted helminths in the TUMIKIA trial, Kenya: a secondary longitudinal analysis

SummaryBackgroundFew studies have been done of patterns of treatment during mass drug administration (MDA) to control neglected tropical diseases. We used routinely collected individual-level treatment records that had been collated for the Tuangamize Minyoo Kenya Imarisha Afya (Swahili for Eradicate Worms in Kenya for Better Health [TUMIKIA]) trial, done in coastal Kenya from 2015 to 2017. In this analysis we estimate the extent of and factors associated with the same individuals not being treated over multiple rounds of MDA, which we term systematic non-treatment.MethodsWe linked the baseline population of the TUMIKIA trial randomly assigned to receive biannual community-wide MDA for soil-transmitted helminthiasis to longitudinal records on receipt of treatment in any of the four treatment rounds of the study. We fitted logistic regression models to estimate the association of non-treatment in a given round with non-treatment in the previous round, controlling for identified predictors of non-treatment. We also used multinomial logistic regression to identify factors associated with part or no treatment versus complete treatment.Findings36 327 participants were included in our analysis: 16 236 children aged 2–14 years and 20 091 adults aged 15 years or older. The odds of having no treatment recorded was higher if a participant was not treated during the previous round of MDA (adjusted odds ratio [OR] 3·60, 95% CI 3·08–4·20 for children and 5·58, 5·01–6·21 for adults). For children, school attendance and rural residence reduced the odds of receiving part or no treatment, whereas odds were increased by least poor socioeconomic status and living in an urban or periurban household. Women had higher odds than men of receiving part or no treatment. However, when those with pregnancy or childbirth in the previous 2 weeks were excluded, women became more likely to receive complete treatment. Adults aged 20–25 years were the age group with the highest odds of receiving part (OR 1·41, 95% CI 1·22–1·63) or no treatment (OR 1·81, 95% CI 1·53–2·14).InterpretationNon-treatment was associated with specific sociodemographic groups and characteristics and did not occcur at random. This finding has important implications for MDA programme effectiveness, the relevance of which will intensify as disease prevalence decreases and infections become increasingly clustered.FundingBill & Melinda Gates Foundation, Joint Global Health Trials Scheme of the Medical Research Council, UK Department for International Development, Wellcome Trust, Children's Investment Fund Foundation, and London Centre for Neglected Tropical Diseases.

Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study

BackgroundThe 2013–16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus.MethodsIn this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for antibody quantification by ELISA, functional neutralising antibody analysis using live Zaire ebolavirus, and T cell phenotype studies. We report on the longitudinal cellular and humoral response among Ebola virus disease survivors and highlight potentially paucisymptomatic infection.FindingsWe recruited 117 survivors of Ebola virus disease, 66 contacts, and 23 negative controls. The mean neutralising antibody titre among the Ebola virus disease survivors 3–14 months after infection was 1/174 (95% CI 1/136—1/223). Individual results varied greatly from 1/10 to more than 1/1000 but were on average ten times greater than that induced after 1 month by single dose Ebola virus vaccines. Following reactivation with glycoprotein peptide, the mean T cell responses among 116 Ebola virus disease survivors as measured by ELISpot was 305 spot-forming units (95% CI 257–353). The dominant CD8+ polyfunctional T cell phenotype, as measured among 53 Ebola virus disease survivors, was interferon γ+, tumour necrosis factor+, interleukin-2–, and the mean response was 0·046% of total CD8+ T cells (95% CI 0·021–0·071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection.InterpretationThe continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection.FundingUS Food & Drug Administration, Horizon 2020 EU EVIDENT, Wellcome, UK Department for International Development.

Effect of delays in concordant antibiotic treatment on mortality in patients with hospital-acquired Acinetobacter spp. bacteremia in Thailand: a 13-year retrospective cohort

Background: A quantitative understanding of the impact of delays to concordant antibiotic treatment on patient mortality is important for designing hospital antibiotic policies. Acinetobacter spp are among the most prevalent pathogens causing multidrug-resistant hospital-acquired infections in developing countries. We aimed to determine the causal effect of delays in concordant antibiotic treatment on 30-day survival of patients with hospital-acquired Acinetobacter spp bacteremia in a resource-limited setting. Methods: We included patients with Acinetobacter spp–related hospital-acquired bacteremia (HAB) in a hospital in Thailand over a 13-year period. We classified patients into 4 groups: those with no delays to concordant antibiotic treatment; those with a 1-day delay; those with 2-day delays; and those with &gt;2 days of delay. We adopted an analytical approach that aimed to emulate a randomized controlled trial and compared the expected potential outcomes of patients between the exposure groups using a marginal structural model with inverse-probability weightings to adjust for confounders and immortal time bias. Results: Between January 2003 and December 2015, 1,203 patients had HAB with Acinetobacter spp., of which 682 patients (56.7%) had ≥1 days of delay in concordant antibiotic treatment. These delays were associated with an absolute increase in 30-day mortality of 6.6% (95% CI 0.2%-13.0%), from 33.8% to 40.4%. Among the 1,203 patients, 521 had no delays to concordant antibiotic treatment (i.e. concordant therapy on the day of blood collection), 224 patients had a 1-day delay, 119 had a 2-day delay, and 339 had a delay of ≥3 days. The crude 30-day mortality was substantially lower in patients with ≥3 days of delay in concordant treatment compared to those with 1 to 2-days of delays. After adjusting for measured confounders and immortal time bias, the expected probability of dying in the hospital within 30-days of blood collection if patient had no delays in concordant therapy was 39.7% (95% CI: 32.3-47.2%), for a 1-day delay it was 42.7% (95% CI: 29.8-55.7%), for a 2-day delay it was 51.0% (95% CI: 38.9-63.2%), and for a ≥3 days was 40.9% (36.0-45.7%).Conclusions: Delays to concordant antibiotic therapy are linked to increased mortality among patients with HAB due to Acinetobacter spp. Accounting for confounders and immortal time bias is necessary when attempting to estimate causal effects of delayed concordant treatment and, in this case, it helped resolve paradoxical results in crude data.Funding: The Mahidol Oxford Tropical Medicine Research Unit (MORU) is funded by the Wellcome Trust [grant number 106698/Z14/Z]. CL is funded by a Wellcome Trust Research Training Fellowship [grant number 206736/Z/17/Z]. MY is supported by a Singapore National Medical Research Council Research Fellowship [grant number NMRC/Fellowship/0051/2017]. BSC is funded by the UK Medical Research Council and Department for International Development [grant number MR/K006924/1]. DL is funded by a Wellcome Trust Intermediate Training Fellowship [grant number 101103]. The funder has no role in the design and conduct of the study, data collection, or in the analysis and interpretation of the data.Disclosures: None

Clinical and laboratory predictors of 30-day mortality in severe acute malnourished children with severe pneumonia.

To determine the predictors of mortality within 30days of hospital admission in a diarrhoeal disease hospital in Bangladesh. Cohort study of hospitalised children aged 0-59months with severe acute malnutrition (SAM) and severe pneumonia in Dhaka Hospital, icddr,b, Bangladesh from April 2015 to March 2017. Those discharged were followed up, and survival status at 30days from admission was determined. Children who died were compared with the survivors in terms of clinical and laboratory biomarkers. Multivariable logistic regression analysis was used for calculating adjusted odds ratio for death within 30days of hospital admission. We enrolled 191 children. Mortality within 30days of admission was 6% (14/191). After adjusting for potential confounders (hypoxia, CRP and haematocrit) in logistic regression analysis, independent factors associated with death were female sex (aOR=5.80, 95% CI: 1.34-25.19), LAZ <-4 (aOR=6.51, 95% CI: 1.49-28.44) and Polymorphonuclear Leucocytes (PMNL) (>6.0×109 /L) (aOR=1.06, 95% CI: 1.01-1.11). Using sex, Z-score for length for age (LAZ), and PMNL percentage, we used random forest and linear regression models to achieve a cross-validated AUC of 0.83 (95% CI: 0.82, 0.84) for prediction of 30-day mortality. The results of our data suggest that female sex, severe malnutrition (<-4 LAZ) and higher PMNL percentage were prone to be associated with 30-day mortality in children with severe pneumonia. Association of these factors may be used in clinical decision support for prompt identification and appropriate management for prevention of mortality in this population.

Emergency flood bulletins for Cyclones Idai and Kenneth: A critical evaluation of the use of global flood forecasts for international humanitarian preparedness and response

Humanitarian disasters such as Typhoon Haiyan (SE Asia, 2013) and the Horn of Africa drought (2011–2012) are examples of natural hazards that were predicted, but where forecasts were not sufficiently acted upon, leading to considerable loss of life. These events, alongside international adoption of the Sendai Framework for Disaster Risk Reduction, have motivated efforts to enable early action from early warnings. Through initiatives such as Forecast-based Financing (FbF) and the Science for Humanitarian Emergencies and Resilience (SHEAR) programme, progress is being made towards the use of science and forecasts to support international humanitarian organisations and governments in taking early action and improving disaster resilience. However, many challenges remain in using forecasts systematically for preparedness and response. The research community in place through SHEAR enabled the UK government's Department for International Development to task a collaborative group of scientists to produce probabilistic real-time flood forecast and risk bulletins, aimed at humanitarian decision-makers, for Cyclones Idai and Kenneth, which impacted Mozambique in 2019.The process of bulletin creation during Idai and Kenneth is reviewed and critically evaluated, including evaluation of the forecast information alongside evidence for how useful the bulletins were. In this context, this work seeks to navigate the “murky landscape” of national and international mandates, capacities, and collaborations for forecasting, early warning and anticipatory action, with the ultimate aim of finding out what can be done better in the future. Lessons learnt and future recommendations are discussed to enable better collaboration between producers and users of forecast information.

Estimating burden of foodborne diseases where public health impact is higher and data scarcer: a study in four African countries

Abstract Low and middle-income countries, in particular from Africa, bear the highest burden of foodborne disease (FBD). However, because research and disease surveillance data from Africa are limited, previous burden estimates are subject to uncertainty. The main challenge to estimating burden of FBD in Africa is lack of data, where factors ranging from lack of capacity to lack of political commitment, and a focus on priority diseases, limit existing surveillance systems. To address this, we are working with Ethiopia, Mozambique, Nigeria, and Tanzania, to estimate the burden of, and strengthen surveillance systems for, FBD in Africa. We are conducting a population survey (to estimate incidence and distribution of diarrhea in the community), a systematic literature review (to estimate proportions of diarrheal disease caused by different agents), and an active review of available FBD reports (to estimate the extent of under-reporting in existing surveillance). Together, these findings will provide more accurate estimates of the burden of FBD for African countries. Lessons from this large-scale project can be extrapolated to other countries and regions where the burden is high but data are scarce. We highlight applying leadership attributes, including delegation of duties, setting milestones, regular meetings, transparency, and risk mitigation plans. The leading role of experts in this project helps to reduce hurdles. We have also adapted existing data collection tools for use across our diverse African study populations. We are engaging stakeholders who will use our research outputs, by involving them at all stages of the project. This integrated Knowledge Translation approach is translatable to other settings. These studies are part of FOCAL (Foodborne Disease Epidemiology, Surveillance, and Control in African LMIC), a multi-partner, multi-study project co-funded by the Bill and Melinda Gates Foundation and the United Kingdom's Department for International Development.

Virological failure, HIV-1 drug resistance, and early mortality in adults admitted to hospital in Malawi: an observational cohort study

SummaryBackgroundAntiretroviral therapy (ART) scale-up in sub-Saharan Africa combined with weak routine virological monitoring has driven increasing HIV drug resistance. We investigated ART failure, drug resistance, and early mortality among patients with HIV admitted to hospital in Malawi.MethodsThis observational cohort study was nested within the rapid urine-based screening for tuberculosis to reduce AIDS-related mortality in hospitalised patients in Africa (STAMP) trial, which recruited unselected (ie, irrespective of clinical presentation) adult (aged ≥18 years) patients with HIV-1 at admission to medical wards. Patients were included in our observational cohort study if they were enrolled at the Malawi site (Zomba Central Hospital) and were taking ART for at least 6 months at admission. Patients who met inclusion criteria had frozen plasma samples tested for HIV-1 viral load. Those with HIV-1 RNA of at least 1000 copies per mL had drug resistance testing by ultra-deep sequencing, with drug resistance defined as intermediate or high-level resistance using the Stanford HIVDR program. Mortality risk was calculated 56 days from enrolment. Patients were censored at death, at 56 days, or at last contact if lost to follow-up. The modelling strategy addressed the causal association between HIV multidrug resistance and mortality, excluding factors on the causal pathway (most notably, CD4 cell count, clinical signs of advanced HIV, and poor functional and nutritional status).FindingsOf 1316 patients with HIV enrolled in the STAMP trial at the Malawi site between Oct 26, 2015, and Sept 19, 2017, 786 had taken ART for at least 6 months. 252 (32%) of 786 patients had virological failure (viral load ≥1000 copies per mL). Mean age was 41·5 years (SD 11·4) and 528 (67%) of 786 were women. Of 237 patients with HIV drug resistance results available, 195 (82%) had resistance to lamivudine, 128 (54%) to tenofovir, and 219 (92%) to efavirenz. Resistance to at least two drugs was common (196, 83%), and this was associated with increased mortality (adjusted hazard ratio 1·7, 95% CI 1·2–2·4; p=0·0042).InterpretationInterventions are urgently needed and should target ART clinic, hospital, and post-hospital care, including differentiated care focusing on patients with advanced HIV, rapid viral load testing, and routine access to drug resistance testing. Prompt diagnosis and switching to alternative ART could reduce early mortality among inpatients with HIV.FundingJoint Global Health Trials Scheme of the Medical Research Council, UK Department for International Development, and Wellcome Trust.

Using novel methodologies to support burden of disease estimates

Abstract A challenge to estimating burden of diarrheal diseases, particularly in LMICs, where laboratory capacity and surveillance systems are limited, is obtaining valid estimates of etiology proportions of cases. A commonly used method is systematic review of studies reporting pathogen isolation in diarrhea cases. However, studies often differ in design, source population, timeframe, and pathogens included, hampering extrapolation to the target population. In a study co-funded by the Bill and Melinda Gates Foundation and the UK Department for International Development, we explore a novel approach for estimating diarrhea etiology proportions in urban and rural populations in four African countries. We analyse sewage samples using short-read next-generation sequencing (NGS) to determine abundance of genes that can be mapped to specific bacterial genera, providing an estimate of the relative abundance of specific pathogens in each sample. In parallel to collecting sewage samples, a questionnaire-based population survey will estimate diarrheal incidence. By combining results, pathogen-specific incidence will be estimated and compared with incidence estimates from the traditional approach. The application NGS to human sewage has great potential for surveillance of foodborne infections, particularly in resource-poor settings where laboratory capacity for bacterial isolation is limited. First, NGS is a one method takes all approach, as it is based on detection of RNA/DNA, a language common across pathogens. Second, it is culture independent, allowing for real-time data generation and standardized sharing. Finally, few samples are needed to survey large populations for several pathogens at the same time. Thus, surveillance based on NGS of sewage may prove to be an indirect measure of incidence. Although it will not provide an estimate for the true incidence in the population, it will increase our understanding of the burden and as such be a proxy and novel way of ranking diseases.

Exploring the socio-cultural factors in the implementation of public financial management information system in Ghana

PurposeThis paper aims to explore the socio-cultural factors that emerge in the implementation of integrated financial management information systems (IFMIS) in Ghana, a developing country.Design/methodology/approachA qualitative research approach was used with a case study design. The data were collected from archival documents and semi-structured face-to-face interviews with participants who played a significant role in the implementation of IFMIS in the Ghanaian public sector.FindingsThe findings show that although IFMIS was considered by the World Bank, Department for International Development (DFID), European Union and Danish International Development Agency to be rational, technical, universal and unproblematic, the use of the system in the Ghanaian public institutions was constrained by socio-cultural factors. These factors included power struggles between various technocrats; and negative attitudes such as opportunism and rent-seeking interest towards the IFMIS.Research limitations/implicationsThe research is grounded in a single case study, but the findings can be theoretically generalised to information technology (IT)-based financial management system exhibiting the same characteristics.Practical implicationsThis study offers a practical implication for governments, consultants and donor agencies.Originality/valueThis study provides additional insight through the application of the sociology and duality of information technology theory to study a particular IT-based public financial management initiative.

Universal test-and-treat in Zambian and South African correctional facilities: a multisite prospective cohort study

Despite the global scale-up of antiretroviral therapy (ART), incarcerated people have not benefited equally from test-and-treat recommendations for HIV. To improve access to ART for incarcerated people with HIV, we introduced a universal test-and-treat (UTT) intervention in correctional facilities in South Africa and Zambia, and aimed to assess UTT feasibility and clinical outcomes. Treatment as Prevention (TasP) was a multisite, mixed methods, implementation research study done at three correctional complexes in South Africa (Johnannesburg and Breede River) and Zambia (Lusaka). Here, we report the clinical outcomes for a prospective cohort of incarcerated individuals who were offered the TasP UTT intervention. Incarcerated individuals were eligible for inclusion if they were aged 18 years or older, with new or previously diagnosed HIV, not yet on ART, and were expected to remain incarcerated for 30 days or longer. To enable the implementation of UTT at the included correctional facilities, we first strengthened on-site HIV service delivery. All participants were offered same-day ART initiation, and had two study-specific follow-up visits scheduled to coincide with routine clinic visits at 6 and 12 months. The main outcomes were ART uptake, time from cohort enrolment to ART initiation, and retention in care and viral suppression at 6 and 12 months. We estimated the association between baseline demographic characteristics and time to ART initiation using Cox proportional hazard models, and, in a post-hoc analysis, we used logistic regression models to assess the association between demographic and clinical variables, including time to ART initiation, and the proportion of participants with a composite poor outcome (defined as viral load >50 copies per mL, or for participants with a missing viral load, lack of retention in care in the on-site ART programme) at 6 months. This study is registered at ClinicalTrials.gov, NCT02946762. Between June 23, 2016, and Dec 31, 2017, we identified 1562 incarcerated people with HIV, of whom 1389 (89%) were screened, 1021 (74%) met eligibility criteria, and 975 (95%) were enrolled and followed up to March 31, 2018. At the end of follow-up, 835 (86%) of 975 participants had started ART. Median time from enrolment to ART initiation was 0 days (IQR 0-8). Of 346 participants who remained incarcerated at 6 months, 327 (95%) were retained in care and 269 (78%) had a documented viral load, of whom 262 (97%) achieved viral suppression (<1000 copies per mL). The mortality rate among the 835 participants who had initiated ART was 1·9 per 100 person-years (95% CI 0·9-3·9). No statistically significant associations were identified between any baseline characteristics and time to ART initiation or composite poor outcome. UTT implementation is feasible in correctional settings, and can achieve levels of same-day ART uptake, retention in care, and viral suppression among incarcerated people with HIV that are comparable to those observed in community settings. UK Department for International Development, Swedish International Development Cooperation Agency, Norwegian Agency for Development Cooperation.

Prevalence and distribution of schistosomiasis in human, livestock, and snail populations in northern Senegal: a One Health epidemiological study of a multi-host system

SummaryBackgroundSchistosomiasis is a neglected tropical disease of global medical and veterinary importance. As efforts to eliminate schistosomiasis as a public health problem and interrupt transmission gather momentum, the potential zoonotic risk posed by livestock Schistosoma species via viable hybridisation in sub-Saharan Africa have been largely overlooked. We aimed to investigate the prevalence, distribution, and multi-host, multiparasite transmission cycle of Haematobium group schistosomiasis in Senegal, West Africa.MethodsIn this epidemiological study, we carried out systematic surveys in definitive hosts (humans, cattle, sheep, and goats) and snail intermediate hosts, in 2016–18, in two areas of Northern Senegal: Richard Toll and Lac de Guiers, where transmission is perennial; and Barkedji and Linguère, where transmission is seasonal. The occurrence and distribution of Schistosoma species and hybrids were assessed by molecular analyses of parasitological specimens obtained from the different hosts. Children in the study villages aged 5–17 years and enrolled in school were selected from school registers. Adults (aged 18–78 years) were self-selecting volunteers. Livestock from the study villages in both areas were also randomly sampled, as were post-mortem samples from local abattoirs. Additionally, five malacological surveys of snail intermediate hosts were carried out at each site in open water sources used by the communities and their animals.FindingsIn May to August, 2016, we surveyed 375 children and 20 adults from Richard Toll and Lac de Guiers, and 201 children and 107 adults from Barkedji and Linguère; in October, 2017, to January, 2018, we surveyed 386 children and 88 adults from Richard Toll and Lac de Guiers, and 323 children and 85 adults from Barkedji and Linguère. In Richard Toll and Lac de Guiers the prevalence of urogenital schistosomiasis in children was estimated to be 87% (95% CI 80–95) in 2016 and 88% (82–95) in 2017–18. An estimated 63% (in 2016) and 72% (in 2017–18) of infected children were shedding Schistosoma haematobium–Schistosoma bovis hybrids. In adults in Richard Toll and Lac de Guiers, the prevalence of urogenital schistosomiasis was estimated to be 79% (52–97) in 2016 and 41% (30–54) in 2017–18, with 88% of infected samples containing S haematobium–S bovis hybrids. In Barkedji and Linguère the prevalence of urogenital schistosomiasis in children was estimated to be 30% (23–38) in 2016 and 42% (35–49) in 2017–18, with the proportion of infected children found to be shedding S haematobium–S bovis hybrid miracidia much lower than in Richard Toll and Lac de Guiers (11% in 2016 and 9% in 2017–18). In adults in Barkedji and Linguère, the prevalence of urogenital schistosomiasis was estimated to be 26% (17–36) in 2016 and 47% (34–60) in 2017–18, with 10% of infected samples containing S haematobium–S bovis hybrids. The prevalence of S bovis in the sympatric cattle population of Richard Toll and the Lac de Guiers was 92% (80–99), with S bovis also found in sheep (estimated prevalence 14% [5–31]) and goats (15% [5–33]). In Barkedji and Linguère the main schistosome species in livestock was Schistosoma curassoni, with an estimated prevalence of 73% (48–93) in sheep, 84% (61–98) in goats and 8% (2–24) in cattle. S haematobium–S bovis hybrids were not found in livestock. In Richard Toll and Lac de Guiers 35% of infected Bulinus spp snail intermediate hosts were found to be shedding S haematobium–S bovis hybrids (68% shedding S haematobium; 17% shedding S bovis); however, no snails were found to be shedding S haematobium hybrids in Barkedji and Linguère (29% shedding S haematobium; 71% shedding S curassoni).InterpretationOur findings suggest that hybrids originate in humans via zoonotic spillover from livestock populations, where schistosomiasis is co-endemic. Introgressive hybridisation, evolving host ranges, and wider ecosystem contexts could affect the transmission dynamics of schistosomiasis and other pathogens, demonstrating the need to consider control measures within a One Health framework.FundingZoonoses and Emerging Livestock Systems programme (UK Biotechnology and Biological Sciences Research Council, UK Department for International Development, UK Economic and Social Research Council, UK Medical Research Council, UK Natural Environment Research Council, and UK Defence Science and Technology Laboratory).