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Abstract An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T cell help and improve antibody production against HIV-1. To test this, we developed an innovative conjugate vaccine regimen that used a modified vaccinia virus Ankara (MVA) co-expressing HIV-1 envelope (Env) and the hepatitis B virus surface antigen (HBsAg) as a prime, followed by two Env–HBsAg conjugate protein boosts. We compared the immunogenicity of this conjugate regimen to matched HIV-1 Env-only vaccines in two groups of 5 juvenile rhesus macaques previously immunized with hepatitis B vaccines in infancy. We found expansion of both HIV-1 and HBsAg-specific circulating T follicular helper cells and elevated serum levels of CXCL13, a marker for germinal center activity, after boosting with HBsAg–Env conjugate antigens in comparison to Env alone. The conjugate vaccine elicited higher levels of antibodies binding to select HIV Env antigens, but we did not observe significant improvement in antibody functionality, durability, maturation, or B cell clonal expansion. These data suggests that conjugate vaccination can engage both HIV-1 Env and HBsAg specific T cell help and modify antibody responses at early time points, but more research is needed to understand how to leverage this strategy to improve the durability and efficacy of next-generation HIV vaccines.

[Objetivo] El objetivo fue determinar cuál de las dos especies de hidras (Hydra attenuata o Hydra viridis) resultaba más sensible a dos plaguicidas, para luego usarla como parte de la batería de organismos de prueba del Laboratorio de Estudios Ecotoxicológicos (ECOTOX). [Metodología] Para esto se utilizaron diluciones de dos de los plaguicidas más comúnmente usados en el cultivo de piña en Costa Rica y detectados en muestras de agua: el herbicida diuron y el insecticida etoprofos. Se realizaron bioensayos de toxicidad con cada una de estas sustancias y con una mezcla de estas. Se registró el estado morfológico de las hidras. Además, se evaluaron la concentración de efecto medio (EC50), la concentración letal media (LC50), y las interacciones de toxicidad según tres posibilidades: antagónica, aditiva o sinérgica. [Resultados] La H. attenuata fue la especie más sensible a ambos plaguicidas, con LC50s de 16,84 mg/L y 103,01 mg/L; y EC50s de 4,24 mg/L y 23,74 mg/L para diuron y etoprofos, respectivamente. Mientras tanto la H. viridis tuvo LC50s de 36,94 mg/L y 103,01 mg/L, con EC50s de 13,64 mg/L y 53,12 mg/L, también para diuron y etoprofos, respectivamente. La exposición a la mezcla de plaguicidas solo causó mortalidad a la H. viridis y tuvo efecto sinérgico en ambas especies. [Conclusiones] Estos resultados sugieren que la H. attenuata es la especie más apropiada para la evaluación de efectos de plaguicidas, pero se deben realizar más estudios sobre las interacciones de los contaminantes en mezclas, porque estas pueden modificar su toxicidad para diferentes especies.

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P

Background Opioid overprescribing is commonplace after total hip (THA) and total knee arthroplasty (TKA). Preliminary data demonstrated that approximately 32% of the opioids prescribed at discharge from our hospital following THA and TKA remain unused. This is a concern given that unused prescribed opioids are available for diversion and may result in misuse and abuse.Methods Pre-intervention data were collected between 1 November 2018 and 10 December 2018. An intervention bundle was then introduced, including education of patients and providers, a standardised pain management algorithm and an autopopulated discharge prescription. The aim of this quality improvement initiative was to reduce the amount of opioid (average oral morphine equivalents (OME)) dispensed (based on the discharge prescription provided) following THA and TKA at our institution by 15% by 1 April 2019.Design Using an interrupted time series design, the outcome measure was the amount of opioid (OME) dispensed from the discharge prescription provided. Process measures included the percentage of autopopulated discharge prescriptions, the percentage of patients receiving education at discharge and the percentage of nurses and residents receiving standardised education. Balancing measures included patient satisfaction with postoperative pain management, and the percentage of patients filling the second half of the part-fill or requiring a subsequent opioid prescription.Results With 600 patients identified, mean OME dispensed at discharge was reduced by 26.3% (from 522.2 to 384.9 mg) after our interventions started. Utilisation of autopopulated part-fill prescriptions was 95.8%. There was no change in patient satisfaction nor in the proportion of patients requiring an additional opioid prescription post-intervention. Only 39% of patients filled the second half of the part-fill prescription post-intervention.Conclusions Mean OME dispensed at discharge per patient was reduced with no change in patient satisfaction after introduction of the intervention bundle.

Abstract Introduction To understand when knowledge objects in a computable biomedical knowledge library are likely to be subject to regulation as a medical device in the United Kingdom. Methods A briefing paper was circulated to a multi‐disciplinary group of 25 including regulators, lawyers and others with insights into device regulation. A 1‐day workshop was convened to discuss questions relating to our aim. A discussion paper was drafted by lead authors and circulated to other authors for their comments and contributions. Results This article reports on those deliberations and describes how UK device regulators are likely to treat the different kinds of knowledge objects that may be stored in computable biomedical knowledge libraries. While our focus is the likely approach of UK regulators, our analogies and analysis will also be relevant to the approaches taken by regulators elsewhere. We include a table examining the implications for each of the four knowledge levels described by Boxwala in 2011 and propose an additional level. Conclusions If a knowledge object is described as directly executable for a medical purpose to provide decision support, it will generally be in scope of UK regulation as “software as a medical device.” However, if the knowledge object consists of an algorithm, a ruleset, pseudocode or some other representation that is not directly executable and whose developers make no claim that it can be used for a medical purpose, it is not likely to be subject to regulation. We expect similar reasoning to be applied by regulators in other countries.

Abstract Background Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission. Methods A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTs Discussion The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission Trial registration ClinicalTrials.gov NCT04966702 . Registered on July 19, 2021. Pan African Clinical Trials Registry PACTR202106695877303.

Abstract Background The 2013 WHO guidelines for nutritional rehabilitation of malnourished infants under six months (u6m) focus on inpatient re-establishment of exclusive breastfeeding and recommends discharge when infant is gaining weight on breastmilk alone. Guided by a breastfeeding support tool, breastfeeding peer supporters (BFPS) can support implementation of these guideline by providing continuous individualised breastfeeding counselling to mothers of malnourished infants u6m. Recording and sharing information plays an important role in shaping in-patient care but little is known about recording practices for inpatient nutrition rehabilitation of infants u6m or how such practices affect care. We set out to explore introduction of BFPS into hospitals, and how it shaped the recording and practices of care for acutely malnourished infants u6m. Methods We applied a descriptive, exploratory design involving a pre and during intervention audit of the infant u6m inpatient records in two hospitals in Kenya, as well as pre- and post-intervention in-depth interviews with health workers involved in the care of admitted infants u6m. We developed an audit tool and used it to extract routine data on patient information from hospital records. Data were entered into a REDCap database and analyzed using STATA 17.0 software. We conducted thirty in-depth interviews with health workers exploring their care practices and their perceived effect of the presence of the BFPS on health workers treatment practices. We analysed interview data using thematic framework approach. Results A total of 170 and 65 inpatient files were available for the audit during the pre- and post-intervention period respectively. The presence of the BFPS seemed to have encouraged the recording of (i) breastfeeding status upon admission, (ii) breastfeeding management plan and (iii) reporting of its implementation and progress during treatment. The breastfeeding peer support intervention had a positive impact on breastfeeding recording and reporting practices. Health workers reported that the BFPS facilitated the recording of observed breastfeeding data and how their records influenced final inputs of breastfeeding support provided in the inpatient file. Conclusions Guideline implementation tools facilitate effective application of guidelines and should accompany any guideline formulation process and have their effectiveness at recording and monitoring progress evaluated.

Abstract Background The housing stock of rural sub-Saharan Africa is changing rapidly. With millions of new homes required over the coming decades, there is an opportunity to protect residents by screening homes from malaria mosquitoes. This study, undertaken in the Upper River Region of The Gambia, explores local perceptions of what a good house should provide for its inhabitants and responses to living in a house that has been modified as part of a randomized control trial designed to assess whether improved housing provided additional protection against clinical malaria in children (the RooPfs trial). Methods This descriptive, exploratory study was undertaken over 22 months using mixed-methods (informal conversations, observations, focus group discussions, photovoice, and a questionnaire survey) in a parallel convergent design. Analysis was conducted across the data sets using a framework approach. Following coding, the textual data were charted by a priori and emerging themes. These themes were compared with the quantitative survey results. The nature and range of views about housing and the RooPfs study modifications and the relationships among them were identified and described. Results The data were derived from a total of 35 sets of observations and informal conversations in 10 villages, 12 discussions with the photovoice photographers, 26 focus group discussions (across 13 villages) and 391 completed questionnaires. The study participants described a ‘good house’ as one with a corrugate-metal roof, cement walls (preferably cement block, but mud block covered with cement plaster was also an acceptable and cheaper substitute) and well-fitting doors. These features align with local perceptions of a modern house that provides social status and protection from physical harms. The RooPfs modifications were largely appreciated, although poor workmanship caused concerns that houses had become insecure. However, the long-term trusting relationship with the implementing institution and the actions taken to rectify problems provided reassurance and enhanced acceptability. Conclusion In developing housing to address population needs in Africa, attention should be paid to local perceptions of what is required to make a house secure for its inhabitants, as well as providing a healthy environment.

Abstract Background Undernourished children in low- and middle-income countries remain at elevated risk of death following hospital discharge, even when treated during hospitalisation using World Health Organisation recommended guidelines. The role of community health workers (CHWs) in supporting post-discharge recovery to improve outcomes has not been adequately explored. Methods This paper draws on qualitative research conducted as part of the Childhood Acute Illnesses and Nutrition (CHAIN) Network in Bangladesh and Kenya. We interviewed family members of 64 acutely ill children admitted across four hospitals (a rural and urban hospital in each country). 27 children had severe wasting or kwashiorkor on admission. Family members were interviewed in their homes soon after discharge, and up to three further times over the following six to fourteen months. These data were supplemented by observations in facilities and homes, key informant interviews with CHWs and policy makers, and a review of relevant guidelines. Results Guidelines suggest that CHWs could play a role in supporting recovery of undernourished children post-discharge, but the mechanisms to link CHWs into post-discharge support processes are not specified. Few families we interviewed reported any interactions with CHWs post-discharge, especially in Kenya, despite our data suggesting that opportunities for CHWs to assist families post-discharge include providing context sensitive information and education, identification of danger signs, and supporting linkages with community-based services and interventions. Although CHWs are generally present in communities, challenges they face in conducting their roles include unmanageable workloads, few incentives, lack of equipment and supplies and inadequate support from supervisors and some community members. Conclusion A multi-pronged approach before or on discharge is needed to strengthen linkages between CHWs and children vulnerable to poor outcomes, supported by clear guidance. To encourage scale-ability and cost-effectiveness of interventions, the most vulnerable, high-risk children, should be targeted, including undernourished children. Intervention designs must also take into account existing health worker shortages and training levels, including for CHWs, and how any new tasks or personnel are incorporated into hospital and broader health system hierarchies and systems. Any such interventions will need to be evaluated in carefully designed studies, including tracking for unintended consequences.

Characterizing older adult engagement is important to determine the effectiveness of interventions. Engagement refers to the occupying of oneself in external stimuli and is observable across multiple dimensions of behavior. Engagement of older adults is commonly investigated using a single behavioral dimension. There is a dearth of analytical methods that can simultaneously quantify both verbal and non-verbal forms of communication as proxies for engagement. In this article, we present a multidimensional technique to measure engagement of older adults using techniques appropriate for people with varying degrees of dementia. The new analytical approach measures facial movement, lexical use, and prosodic patterns of speech as indices of affective and behavioral outcomes of engagement. Contexts for engagement included a dyadic reminiscence therapy interview and a 12-week technology-driven group reminiscence therapy. Illustrative examples of the technique are described by two participants from two different groups in a naturalistic setting. Application of these analytical techniques can enhance measurement precision and further develop the science and evidence base, especially for, but not confined to, non-pharmacological interventions.

BackgroundThe growing ethical requirement to engage communities with health research has yielded diversification in approaches and targeted audiences. Conventional approaches like community “town-hall meetings,” laboratory open-days and focus group discussions, have evolved into new methods and audiences such as community drama and school engagement with health research (SEHR) involving learning interactions between researchers and school students. While engagement practices are diversifying, evaluations of these initiatives are rare in Low- and Middle-Income Countries (LMIC). This article focuses on the use of Participatory Video (PV) to explore the influence of the KEMRI-Wellcome Trust Research Programme's (KWTRP) School Engagement Programme (SEP) on the views and understandings of science and research among Kenyan state secondary school students.MethodsTwelve male and twelve female students from four coeducational schools were provided with film-making kits (1 per school), and a one-day PV training workshop. They prepared 22 short films over 8 weeks depicting their experiences and views of research and engagement and conveying their career aspirations. Schools were selected based on prior SEP participation; two schools having experienced different engagement approaches, and the others with no prior school engagement. Study data comprised footage and participant observation notes.ResultsPV provided an opportunity to simultaneously engage and evaluate to inform practice. Through student-led filmmaking, PV stimulated conversations with students about research and engagement, enabling them to share their views in a way they felt was appropriate. These interactions offered an understanding of student gains from engagement, the depth of interaction required to address perceptions held about research and the potential unintended consequences of engagement. PV also provided insights into the context and complexity of life in which engagement is situated. Understanding this context is important because of its potential influence on participation in engagement activities. We draw on these insights to make two recommendations for school engagement practice. First is that PV can provide an enjoyable and insightful means of combining engagement with evaluation. Second, given that time for SEHR is competed for against other important curricular and extracurricular activities, SEHR practitioners must ensure that activities are as beneficial and enjoyable as possible to students.

Introduction: Dose escalation to dominant intraprostatic lesions (DILs) is a novel method to increase the therapeutic ratio in localised prostate cancer. The Stereotactic Prostate Augmented Radiotherapy with Cyberknife (SPARC) trial was designed to determine the feasibility of a focal boost defined with multiparametric magnetic resonance imaging (mpMRI) using stereotactic ablative body radiotherapy (SABR). Materials and methods: Patients were included with newly diagnosed intermediate to high risk prostate cancer with at least one of: Gleason score 4 + 3, stage T3a, or PSA > 20 ng/ml. Visible disease on mpMRI was mandatory and up to 2 separate nodules were allowed. All patients received androgen deprivation. Patients received 36.25 Gy in 5 fractions using CyberKnife® and the DIL received a simultaneous boost to a maximum of 47.5 Gy, as allowed by OAR constraints. Genitourinary (GU) and gastrointestinal (GI) toxicity was reported using the RTOG scoring criteria. International Index of Erectile Function (IIEF) and EQ-5D global health scores were regularly captured. Results: An interim safety analysis was performed on the first 8 patients, recruited between July 2013 and December 2015. Median follow up was 56 months (range 50–74). Median D95 values for the prostate PTV and boost volume were 36.55 Gy (range 35.87–36.99) and 46.62 Gy (range 44.85–48.25) respectively. Of the dose constraints, 10/80 were not achieved but all were minor dose variations. Grade 2+ acute GU and GI toxicities were 37.5% respectively while grade 2+ late GU and GI toxicities were 12.5% and 0% respectively. IIEF and quality of life scores recovered over time and all patients remain in biochemical remission. Conclusion: The first patients have been successfully treated with prostate SABR and focal boost on the SPARC trial, with excellent adherence to the planning protocol. Toxicity and efficacy results are promising and further recruitment is underway.

Abstract Background The 2013 updated guidelines on management of severe acute malnutrition in infants and children recommends the support of exclusive breastfeeding. These guidelines are inconsistently applied in low and middle income countries (LMICs) due to barriers including unclear implementation guides, technical support and epidemiological factors. Peer support strategies have been used to offer psychological support to families with infants in NICU and improve mental health outcomes. Breastfeeding peer supporters (BFPS) have been shown to be effective in improving breastfeeding outcomes in community settings however, their success within hospital settings in LMICs is unknown. We conducted a scoping review to explore implementation of breastfeeding peer support strategies as have been applied to hospitalized infants globally and highlight their implementation strategies in order to guide future research and practice. Methods A scoping review of the literature was conducted using the Arksey and O’Malley framework. A search was conducted in five online databases (PubMed, Cochrane library, Hinari, Google Scholar and Open Grey library). Data were extracted and charted in data extraction tables to capture general characteristics, modes of peer support delivery, implementation details and evaluation procedures. Results From the online search 276 articles were identified, however only 18 met the inclusion criteria for the study. The majority of these articles were reports on in-patient breastfeeding peer support interventions applied in Europe and the United States of America and only two were from LMICs. The articles described peer supporters’ identification, training (n = 13) and supervision (n = 14). The majority of the BFPS were employed (n = 10) compared to volunteers (n = 3) and support was mainly one-to-one (n = 11) rather than group support. Process and impact evaluation (n = 13) reported positive breastfeeding outcomes associated with breastfeeding peer support. Conclusion Breastfeeding peer support strategies are applied in different hospital settings and can be used to improve breastfeeding outcomes. However, to achieve integration, scalability and comparability of impact and outcomes, there is a need to standardize training, develop consistent implementation and supervision plans of in-patient peer supporters’ strategies. Further research to assess sustainability and evaluate cost-effectiveness of in-patient breastfeeding peer support strategies will improve uptake and scalability of these potentially lifesaving interventions.

Abstract Background Detection of tuberculosis (TB) in children in Kenya is sub-optimal. Xpert MTB/RIF® assay (Xpert®) has the potential to improve speed of TB diagnosis due to its sensitivity and fast turnaround for results. Significant effort and resources have been put into making the machines widely available in Kenya, but use remains low, especially in children. We set out to explore the reasons for the under-detection of TB and underuse of Xpert® in children, identifying challenges that may be relevant to other newer diagnostics in similar settings. Methods This was an exploratory qualitative study with an embedded case study approach. Data collection involved semi-structured interviews; small-group discussions; key informant interviews; observations of TB trainings, sensitisation meetings, policy meetings, hospital practices; desk review of guidelines, job aides and policy documents. The Capability, Opportunity and Motivation (COM-B) framework was used to interpret emerging themes. Results At individual level, knowledge, skill, competence and experience, as well as beliefs and fears impacted on capability (physical & psychological) as well as motivation (reflective) to diagnose TB in children and use diagnostic tests. Hospital level influencers included hospital norms, processes, patient flows and resources which affected how individual health workers attempted to diagnose TB in children by impacting on their capability (physical & psychological), motivation (reflective & automatic) and opportunity (physical & social). At the wider system level, community practices and beliefs, and implementation of TB programme directives impacted some of the decisions that health workers made through capability (psychological), motivation (reflective & automatic) and opportunity (physical). Conclusion We used comprehensive approaches to identify influencers of TB case detection and use of TB diagnostic tests in children in Kenya. These results are being used to design a contextually-appropriate intervention to improve TB diagnosis, which may be relevant to similar low-resource, high TB burden countries and can be feasibly implemented by the National TB programme.

Abstract Background Recording behaviours that have the potential to impact health can be doubly challenging if the behaviour takes place in private spaces that cannot be observed directly, and where respondents answer what they think the recorder may want to hear. Sleeping under a long-lasting insecticidal net (LLIN) is an important intervention for malaria prevention, yet it is difficult to gauge the extent to which coverage (how many nets are in the community) differs from usage (how many people actually sleep under a net). List randomization, a novel method which partially obscures respondents’ answers to sensitive questions, was employed to estimate LLIN usage in The Gambia. Methods 802 heads-of-household from 15 villages were recruited into a randomized controlled trial assessing the effect of a housing intervention on malaria. These houses were randomly assigned to a housing intervention versus control, with stratification by village so as to ensure balance between arms. From these, 125 households (63 intervention, 52 control) were randomly selected for participation in the list randomization experiment, along with 68 households from the same villages but which were not part of the housing improvement study, resulting in a total of 196 households for the list randomization experiment. Approximately half (n = 97) of the 196 study participants were randomly assigned to the control group and received a four-question list about non-sensitive behaviours; the intervention group (n = 99) received the same list, with the addition of one question on a sensitive behaviour: whether or not they had used a bed net the previous night. Participants were read the list of questions and then said how many of the statements were true. Bed net usage was estimated by calculating the difference in means between the number of affirmative responses between the two groups. Results The mean number of affirmative responses in the control group was 2.60 of four statements (95% confidence interval, 95% CI 2.50–2.70), compared with 3.68 (95% CI 3.59–3.78) in the intervention group. Such difference (1.08; 95% CI 94.9–100%) suggests near universal bed net usage. Conclusions Bed net usage by household heads in these rural villages was found to be high. Though not entirely unexpected given other studies’ estimates of high bed net usage in the area, the list randomization method should be further validated in an area with lower coverage.

Abstract Background The 2013 WHO guidelines for nutritional rehabilitation of hospitalized and non-hospitalized malnourished infants under six months (u6m) recommend the re-establishment of exclusive breastfeeding. However, in most low-income settings these recommendations are not consistently applied. A recently concluded pilot study on the effects of implementing these guidelines among hospitalized malnourished infants u6m of age in Kilifi, Kenya introduced breastfeeding peer supporters (BFPS) to the inpatient setting to support guideline implementation. Here we report a sub-study investigating mothers’ experiences and perceptions of the process of re-establishing exclusive breastfeeding during their infant’s admission to hospital. Methods Interviews were conducted with mothers just prior to their infant’s discharge to explore their experiences and perceptions of the breastfeeding support process. A trained social science researcher conducted the interviews in Kiswahili language using a structured interview guide with open questions. Interviews were tape recorded, transcribed and translated into English for analysis. Data were managed and organized using NVIVO version 10 and analyzed using a framework approach. Results Twenty mothers were interviewed. While some mothers found re-establishing breastfeeding challenging, they all reported improved knowledge on the relationships between maternal nutrition, stress management, hygiene practices and breastmilk production. They also reported gaining skills in breast care, breastfeeding techniques, hand expression and handling of expressed breastmilk. The breastfeeding peer supporters were said to have provided technical, social and emotional support which facilitated the process of re-establishing exclusive breastfeeding. The mothers identified the key characteristics of an effective and trustworthy BFPS as well as gaps in support. Conclusion BFPS are able share knowledge and skills in a way that is understood and appreciated by the mothers of inpatient malnourished infants u6m of age, enhancing the reestablishment of exclusive breastfeeding. Central to the success of BFPS is their ability to develop close and supportive relationships with the mothers based on shared social and cultural backgrounds. Future studies should focus on evaluating the long-term impact of inpatient breastfeeding support strategies on the quality of breastfeeding and growth, as well as on understanding where, when and how BFPS might be incorporated into routine hospital settings.

Abstract Aims and Objectives Neonatal inpatient care is reliant on experienced nursing care, yet little is known about how Kenyan hospitals foster the development of newborn nursing experience in newborn units. Design A Qualitative ethnographic design. Methods Face to face 29 in depth interviews were conducted with nurses providing neonatal care in one private, one faith based and one public hospital in Nairobi, Kenya between January 2017 and March 2018. All data were transcribed verbatim, coded in the original language and analysed using a framework approach. Results Across the sectors, nurses perceived experience as important to the provision of quality care. They noted that hospitals could foster experience through recruitment, orientation, continuous learning and retention. However, while the private hospital facilitated experience building the public and faith‐based hospitals experienced challenges due to human resource management practices and nursing shortages. Conclusion Health sector context influenced how experience was developed among nurses. Implications Nurturing experience will require that different health sectors adopt better recruitment for people interested in NBU work, better orientation and fewer rotations even without specialist nurse training.

Abstract Background Exclusive breastfeeding up to 6 months of age is recommended by the World Health Organization as the optimal mode of infant feeding, providing adequate nutrition for the baby and protection against infectious diseases. Breastfeeding can be adversely affected by individual, cultural and socio-economic factors. The study aimed to explore barriers of exclusive breastfeeding in the first 6 months of life among first-time mothers in rural Kenya. Methods An observational longitudinal design aimed to provide rich data on breastfeeding behaviour. Twenty pregnant first-time mothers were recruited through antenatal clinics and snowballing. Mothers were visited nine times at home from late pregnancy, at 1 week and 2 weeks post-delivery, then monthly until the baby was aged 6 months. Visits were conducted between November 2016 and April 2018. At the first visit, participants were asked about breastfeeding intentions and infant feeding education received. At each postnatal visit, direct observation of breastfeeding, a recorded semi-structured interview on feeding, mother’s and baby’s health was performed. Interviews were transcribed, checked, content was grouped into categories and analyzed using a qualitative descriptive approach. Results Most participants were adolescent (75%) and unmarried (65%). All 20 mothers intended to and did breastfeed, however additional fluids and semi-solids were commonly given. Only two mothers exclusively breastfed from birth up to 6 months of age. Prelacteal feeds, home remedies and traditional medicine were given by over a third of mothers in the first week of life. Concern over babies’ bowel habits and persistent crying perceived as abdominal colic led to several mothers receiving advice to give gripe water and traditional remedies. Early introduction of maize porridge from 3 months of age because of perceived hunger of the child was recommended by other family members. Breastfeeding observation showed persistent problems with positioning and attachment of infants. Conclusions Exclusive breastfeeding from birth to 6 months was uncommon. Prioritization of capacity to detect mothers with breastfeeding problems and provide breastfeeding education and support is necessary, particularly during the antenatal and early postnatal period. It is important to engage with other women resident in the household who may offer conflicting feeding advice.

Background: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5–7 days during an upper respiratory tract infection reduces the risk of relapse. Objectives: To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none. Design: A randomised double-blind placebo-controlled trial, including a cost-effectiveness analysis. Setting: A total of 122 UK paediatric departments, of which 91 recruited patients. Participants: A total of 365 children with relapsing steroid-sensitive nephrotic syndrome (mean age 7.6 ± 3.5 years) were randomised (1 : 1) according to a minimisation algorithm based on background treatment. Eighty children completed 12 months of follow-up without an upper respiratory tract infection. Thirty-two children were withdrawn from the trial (14 prior to an upper respiratory tract infection), leaving a modified intention-to-treat analysis population of 271 children (134 and 137 children in the prednisolone and placebo arms, respectively). Interventions: At the start of an upper respiratory tract infection, children received 6 days of prednisolone (15 mg/m2) or an equivalent dose of placebo. Main outcome measures: The primary outcome was the incidence of first upper respiratory tract infection-related relapse following any upper respiratory tract infection over 12 months. The secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention-to-treat principle. The cost-effectiveness analysis used trial data and a decision-analytic model to estimate quality-adjusted life-years and costs at 1 year, which were then extrapolated over 16 years. Results: There were 384 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the prednisolone arm, and 407 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms, respectively (adjusted risk difference –0.024, 95% confidence interval –0.14 to 0.09; p = 0.70). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. Giving daily prednisolone at the time of an upper respiratory tract infection was associated with increased quality-adjusted life-years (0.9427 vs. 0.9424) and decreased average costs (£252 vs. £254), when compared with standard care. The cost saving was driven by background therapy and hospitalisations after relapse. The finding was robust to sensitivity analysis. Limitations: A larger number of children than expected did not have an upper respiratory tract infection and the sample size attrition rate was adjusted accordingly during the trial. Conclusions: The clinical analysis indicated that giving 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of steroid-sensitive nephrotic syndrome in UK children. However, there was an economic benefit from costs associated with background therapy and relapse, and the health-related quality-of-life impact of having a relapse. Future work: Further work is needed to investigate the clinical and health economic impact of relapses, interethnic differences in treatment response, the effect of different corticosteroid regimens in treating relapses, and the pathogenesis of individual viral infections and their effect on steroid-sensitive nephrotic syndrome. Trial registration: Current Controlled Trials ISRCTN10900733 and EudraCT 2012-003476-39. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 3. See the NIHR Journals Library website for further project information.

Abstract Background Routine health information systems can provide near real-time data for malaria programme management, monitoring and evaluation, and surveillance. There are widespread concerns about the quality of the malaria data generated through routine information systems in many low-income countries. However, there has been little careful examination of micro-level practices of data collection which are central to the production of routine malaria data. Methods Drawing on fieldwork conducted in two malaria endemic sub-counties in Kenya, this study examined the processes and practices that shape routine malaria data generation at frontline health facilities. The study employed ethnographic methods—including observations, records review, and interviews—over 18-months in four frontline health facilities and two sub-county health records offices. Data were analysed using a thematic analysis approach. Results Malaria data generation was influenced by a range of factors including human resource shortages, tool design, and stock-out of data collection tools. Most of the challenges encountered by health workers in routine malaria data generation had their roots in wider system issues and at the national level where the framing of indicators and development of data collection tools takes place. In response to these challenges, health workers adopted various coping mechanisms such as informal task shifting and use of improvised tools. While these initiatives sustained the data collection process, they also had considerable implications for the data recorded and led to discrepancies in data that were recorded in primary registers. These discrepancies were concealed in aggregated monthly reports that were subsequently entered into the District Health Information Software 2. Conclusion Challenges to routine malaria data generation at frontline health facilities are not malaria or health information systems specific; they reflect wider health system weaknesses. Any interventions seeking to improve routine malaria data generation must look beyond just malaria or health information system initiatives and include consideration of the broader contextual factors that shape malaria data generation.

Abstract Acute malnutrition in infants under 6 months (u6m) is increasingly recognised as a global public health problem. The World Health Organisation (WHO) guidelines for inpatient nutritional rehabilitation of infants u6m is re‐lactation: the re‐establishment of exclusive breastfeeding. Evidence suggests these guidelines are rarely followed in many low‐income settings. Two studies of infant nutritional rehabilitation undertaken in three public hospitals in coastal Kenya employed breastfeeding peer supporters (BFPSs) to facilitate WHO guideline implementation. To explore the acceptability of the strategy to health workers (HWs) and the BFPSs, in‐depth interviews were conducted with 20 HWs and five BFPSs in the three study hospitals. The HWs reported that the presence of the BFPSs changed the way infant nutritional rehabilitation was managed, increasing efforts at relactation and decreasing reliance on supplemental milk. BFPSs were said to help address staff shortages and had dedicated time to support and assist the mothers. Key to the success of the BFPSs was the social relationships they were able to establish with the mothers due to the similarity in their experiences and backgrounds. Despite the success of the BFPSs, human resource management and infrastructure challenges remained. BFPSs can successfully be employed to facilitate the implementation of the WHO guidelines for the nutritional rehabilitation of acutely malnourished infants u6m in hospitals in Kenya, establishing supportive social relationships and trust with the mothers of the acutely malnourished infants and helping to address the issue of human resource shortages.

Objective Embedding researchers within health systems results in more socially relevant research and more effective uptake of evidence into policy and practice. However, the practice of embedded health service research remains poorly understood. We explored and assessed the development of embedded participatory approaches to health service research by a health research team in Kenya highlighting the different ways multiple stakeholders were engaged in a neonatal research study.Methods We conducted semistructured qualitative interviews with key stakeholders. Data were analysed thematically using both inductive and deductive approaches.Setting Over recent years, the Health Services Unit within the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme in Nairobi Kenya, has been working closely with organisations and technical stakeholders including, but not limited to, medical and nursing schools, frontline health workers, senior paediatricians, policymakers and county officials, in developing and conducting embedded health research. This involves researchers embedding themselves in the contexts in which they carry out their research (mainly in county hospitals, local universities and other training institutions), creating and sustaining social networks. Researchers collaboratively worked with stakeholders to identify clinical, operational and behavioural issues related to routine service delivery, formulating and exploring research questions to bring change in practiceParticipants We purposively selected 14 relevant stakeholders spanning policy, training institutions, healthcare workers, regulatory councils and professional associations.Results The value of embeddedness is highlighted through the description of a recently completed project, Health Services that Deliver for Newborns (HSD-N). We describe how the HSD-N research process contributed to and further strengthened a collaborative research platform and illustrating this project’s role in identifying and generating ideas about how to tackle health service delivery problemsConclusions We conclude with a discussion about the experiences, challenges and lessons learned regarding engaging stakeholders in the coproduction of research.

Analyses of human clinical HIV-1 vaccine trials and preclinical vaccine studies performed in rhesus macaque (RM) models have identified associations between non-neutralizing Fc Receptor (FcR)-dependent antibody effector functions and reduced risk of infection. Specifically, antibody-dependent phagocytosis (ADP) has emerged as a common correlate of reduced infection risk in multiple RM studies and the human HVTN505 trial. This recurrent finding suggests that antibody responses with the capability to mediate ADP are most likely a desirable component of vaccine responses aimed at protecting against HIV-1 acquisition. As use of RM models is essential for development of the next generation of candidate HIV-1 vaccines, there is a need to determine how effectively ADP activity observed in RMs translates to activity in humans. In this study we compared ADP activity of human and RM monocytes and polymorphonuclear leukocytes (PMN) to bridge this gap in knowledge. We observed considerable variability in the magnitude of monocyte and PMN ADP activity across individual humans and RM that was not dependent on FcR alleles, and only modestly impacted by cell-surface levels of FcRs. Importantly, we found that for both human and RM phagocytes, ADP activity of antibodies targeting the CD4 binding site was greatest when mediated by human IgG3, followed by RM and human IgG1. These results demonstrate that there is functional homology between antibody and FcRs from these two species for ADP. We also used novel RM IgG1 monoclonal antibodies engineered with elongated hinge regions to show that hinge elongation augments RM ADP activity. The RM IgGs with engineered hinge regions can achieve ADP activity comparable to that observed with human IgG3. These novel modified antibodies will have utility in passive immunization studies aimed at defining the role of IgG3 and ADP in protection from virus challenge or control of disease in RM models. Our results contribute to a better translation of human and macaque antibody and FcR biology, and may help to improve testing accuracy and evaluations of future active and passive prevention strategies.

Summary: Background: In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. We aimed to assess whether children in The Gambia received an incremental benefit from improved housing, where current best practice of insecticide-treated nets, indoor residual spraying, seasonal malaria chemoprevention in children younger than 5 years, and prompt treatment against clinical malaria was in place. Methods: In this randomised controlled study, 800 households with traditional thatched-roofed houses were randomly selected from 91 villages in the Upper River Region of The Gambia. Within each village, equal numbers of houses were randomly allocated to the control and intervention groups using a sampling frame. Houses in the intervention group were modified with metal roofs and screened doors and windows, whereas houses in the control group received no modifications. In each group, clinical malaria in children aged 6 months to 13 years was monitored by active case detection over 2 years (2016–17). We did monthly collections from indoor light traps to estimate vector densities. Primary endpoints were the incidence of clinical malaria in study children with more than 50% of observations each year and household vector density. The trial is registered at ISRCTN02622179. Findings: In June, 2016, 785 houses had one child each recruited into the study (398 in unmodified houses and 402 in modified houses). 26 children in unmodified houses and 28 children in modified houses did not have at least 50% of visits in a year and so were excluded from analysis. 38 children in unmodified houses were recruited after study commencement, as were 21 children in modified houses, meaning 410 children in unmodified houses and 395 in modified houses were included in the parasitological analyses. At the end of the study, 659 (94%) of 702 children were reported to have slept under an insecticide-treated net; 662 (88%) of 755 children lived in houses that received indoor residual spraying; and 151 (90%) of 168 children younger than 5 years had seasonal malaria chemoprevention. Incidence of clinical malaria was 0·12 episodes per child-year in children in the unmodified houses and 0·20 episodes per child-year in the modified houses (unadjusted incidence rate ratio [RR] 1·68 [95% CI 1·11–2·55], p=0·014). Household vector density was 3·30 Anopheles gambiae per house per night in the unmodified houses compared with 3·60 in modified houses (unadjusted RR 1·28 [0·87–1·89], p=0·21). Interpretation: Improved housing did not provide protection against clinical malaria in this area of low seasonal transmission with high coverage of insecticide-treated nets, indoor residual spraying, and seasonal malaria chemoprevention. Funding: Global Health Trials funded by Medical Research Council, UK Department for International Development, and Wellcome Trust.

Abstract Re‐establishment and maintenance of exclusive breastfeeding (EBF) is recommended by the World Health Organization for the nutritional rehabilitation of malnourished infants under 6 months; however, there is no explicit guidance on how this should be achieved. The IBAMI study—a pilot study conducted in Kilifi, Kenya—implemented these recommendations using an intervention for hospitalized infants and their mothers that included ward‐based breastfeeding peer supporters. This paper explores how the challenges of maintaining EBF are recontextualized after infant hospitalization for malnutrition. Four weeks after discharge, semistructured interviews on experiences of trying to maintain EBF in a postdischarge home setting were conducted with a total of 20 mothers. Although most stated the aspiration of maintaining EBF for 6 months, a range of challenges were reported and not all had successfully maintained EBF post discharge. Reported challenges include the stress of household chores, food insecurity, technical difficulties and social stigma of expressing breast milk, pressure from neighbours and family members to introduce mixed feeding, and needing more community‐based awareness and support. Most of these challenges were specific to the home setting and were not easily surmountable, despite the breastfeeding practices mothers had learned in the ward. Indeed, in some cases, challenges were exacerbated by the overmedicalized nature of the breastfeeding practices taught in the ward. In order to aid the transition from ward to home, there may be a need to further translate ward‐based education and promotional messaging for EBF into a community setting, targeting other caregivers as well.

Summary: Patient-derived cancer organoids hold great potential to accurately model and predict therapeutic responses. Efficient organoid isolation methods that minimize post-collection manipulation of tissues would improve adaptability, accuracy, and applicability to both experimental and real-time clinical settings. Here we present a simple and minimally invasive fine-needle aspiration (FNA)-based organoid culture technique using a variety of tumor types including gastrointestinal, thyroid, melanoma, and kidney. This method isolates organoids directly from patients at the bedside or from resected tissues, requiring minimal tissue processing while preserving the histologic growth patterns and infiltrating immune cells. Finally, we illustrate diverse downstream applications of this technique including in vitro high-throughput chemotherapeutic screens, in situ immune cell characterization, and in vivo patient-derived xenografts. Thus, routine clinical FNA-based collection techniques represent an unappreciated substantial source of material that can be exploited to generate tumor organoids from a variety of tumor types for both discovery and clinical applications.

Background: Kenya has one of the highest rates of neonatal mortality in the world at 22/1,000 live births. Improving the quality of newborn care would greatly improve survival rates. There is an increasing consensus that strong health systems are key to achieving improved health outcomes. However, there is significantly less agreement on what to strengthen in low and middle-income countries such as Kenya. As nurses are the main caregivers in many inpatient settings, efforts aimed at improving the quality of facility care for sick newborn babies need to take into account nurses views and opinions. Our intent in this paper is to describe the current state of the nursing environment and what would be required to improve the quality of those environs from nurses’ perspectives. Methods: Between January 2017 and March 2018, we collected data through non-participant observations, unsolicited conversations and review of admission registers. We also conducted 29 individual in-depth interviews with nurses working in the newborn units (NBU) of a public sector hospital (n=10), a private sector hospital (n=11) and a faith-based hospital (n=8). The interviews were digitally audio recorded, transcribed verbatim and, together with observation notes, analysed using thematic content analysis. Results: Nurses as frontline care givers and intervention intermediaries, irrespective of their work contexts, have similar aspirations, needs and expectations from the health systems of how they should be supported to provide quality inpatient care for newborns. These are about the structure of the work environment, especially human resources for health, and the consequences of inadequate structure. They are also about how care is organised and systems that respond to emergencies. Conclusion: Interventions and investments to improve quality need to be directed towards experienced based co-design where we listen to the problems that nurses experience.

Abstract Background Indigenous infants and children in Australia, especially in remote communities, experience early and chronic otitis media (OM) which is difficult to treat and has lifelong impacts in health and education. The LiTTLe Program (Learning to Talk, Talking to Learn) aimed to increase infants’ access to spoken language input, teach parents to manage health and hearing problems, and support children’s school readiness. This paper aimed to explore caregivers’ views about this inclusive, parent-implemented early childhood program for 0–3 years in an Aboriginal community health context. Methods Data from in-depth, semi-structured interviews with 9 caregivers of 12 children who had participated in the program from one remote Aboriginal community in the Northern Territory are presented. Data were analysed thematically. Caregivers provided overall views on the program. In addition, three key areas of focus in the program are also presented here: speech and language, hearing health, and school readiness. Results Caregivers were positive about the interactive speech and language strategies in the program, except for some strategies which some parents found alien or difficult: such as talking slowly, following along with the child’s topic, using parallel talk, or baby talk. Children’s hearing was considered by caregivers to be important for understanding people, enjoying music, and detecting environmental sounds including signs of danger. Caregivers provided perspectives on the utility of sign language and its benefits for communicating with infants and young children with hearing loss, and the difficulty of getting young community children to wear a conventional hearing aid. Caregivers were strongly of the opinion that the program had helped prepare children for school through familiarising their child with early literacy activities and resources, as well as school routines. But caregivers differed as to whether they thought the program should have been located at the school itself. Conclusions The caregivers generally reported positive views about the LiTTLe Program, and also drew attention to areas for improvement. The perspectives gathered may serve to guide other cross-sector collaborations across health and education to respond to OM among children at risk for OM-related disability in speech and language development.

Abstract Background Adherence to anti-malarial medication is highly variable but frequently suboptimal. Numerous interventions with a variety of methodological approaches have been implemented to address the problem. A recently conducted, randomized, controlled trial in western Kenya evaluated the effects of short message service (SMS) reminders on paediatric adherence to artemether–lumefantrine (AL) and found over 97% adherence rates in both intervention and control arms. The current study was undertaken to explore participants’ experiences in the trial and identify the factors contributing to the high adherence rates. Methods In July 2016, 5 months after the trial completion, focus group discussions (FGDs) were undertaken with caregivers of children who had been treated in the intervention (n = 2) or control (n = 2) arms and who, post-trial, had received malaria treatment from the same facilities. The FGDs explored similarities and differences in perceptions and experiences of the care they received during and after the trial. Results Intervention-arm participants reported that SMS messages were effective dosing reminders. Participants from both arms reported that trial instructions to keep empty AL packs for verification during a home visit by a health worker affected their dosing and adherence practices. Differences between trial and post-trial treatment experiences included: administration of the first AL dose by health workers with demonstration of dispersible tablets dilution; advice on what to do if a child vomited; clear instructions on timing of dosing with efforts made to ensure understanding; and, information that dose completion was necessary with explanation provided. Participants reported that after the trial AL was not available at facilities, constraining their ability to adhere to recommended malaria treatment. They emphasized receiving respectful and personal treatment from trial health workers contributing to perceptions of high quality care and enhanced readiness to adhere to dosing instructions. Conclusions This study highlights the complex range of factors that influence AL adherence. The results suggest that in addition to standardized definitions and measurement of adherence, and the influence of enrolment procedures, AL adherence trials need to take account of how intervention impact can be influenced by differences in the quality of care received under trial and routine conditions.

There are important efforts being made to revitalise Aboriginal languages in Australia, which are both pedagogically and culturally appropriate. This research seeks to expand the current knowledge of the effectiveness of gesturing as a teaching strategy for young children learning the Gathang language. An experimental method was used to investigate the effectiveness of gesture by employing a context in which other variables (e.g., other teaching pedagogies) could be held constant. Participants, age range 4–5.2 years, were taught Gathang nouns with gesture and without gesture, alongside verbal and pictorial instruction. After the teaching sessions, each child was assessed for their receptive and expressive knowledge of the Gathang nouns, at two time points, two days after instruction (post-test 1) and one week after (post-test 2). At post-test 2, children had stronger receptive knowledge for words they had learned with gesture than without. These findings contribute to a growing body of research attesting to the effectiveness of gesture for improving knowledge acquisition amongst learners. In the context of Aboriginal language revitalisation, gesture also aligns with traditional teaching practices and offers a relatively low-cost strategy for helping teachers assist their students in acquiring Aboriginal languages.

Abstract Background Young adolescents and unmarried women in low and middle income countries face challenges in accessing family planning services. One factor likely to limit contraceptive use is the attitude and opinion of local stakeholders such as community leaders and health workers. Much of the existing evidence on this topic focuses on women who have already started childbearing. Using primary qualitative data, we explored individual, community and health provider’s perceptions about using modern contraceptives to delay the first birth in a high fertility setting. Methods A descriptive qualitative study was conducted in Tandahimba district in southern Tanzania between December 2014 and March 2015. We conducted 8 focus group discussions with men and women and 25 in-depth interviews (18 with women, 4 with family planning service providers and 3 with district-level staff). Participants were purposively sampled. Data transcripts were managed and coded using Nvivo 11 software and we employed a thematic framework analysis. Results Three main themes emerged about using modern contraceptives to delay first birth: (1) the social and biological status of the woman (2) the type of contraceptive and (3) non-alignment among national policies for adolescents. Use of modern contraceptives to delay first birth was widely acceptable for women who were students, young, unmarried and women in unstable marriage. But long-acting reversible methods such as implants and intrauterine devices were perceived as inappropriate methods for delaying first birth, partly because of fears around delayed return to fecundity, discontinuation once woman’s marital status changes and permanently limiting future fertility. The support for use of modern contraceptives to delay a first pregnancy was not unanimous. A small number of participants from both rural and urban areas did not approve the use of contraceptive methods before the birth of a first baby at all, not even for students. There was lack of clarity and consistency on the definition of ‘young’ and that had direct implications for access, autonomy in decision-making, confidentiality and consent for young people. Conclusions Women who wish to delay their first birth face challenges related to restrictions by age and method imposed by stakeholders in accessing and provision of modern contraceptives. There is a need for a clearly communicated policy on minimum age and appropriate method choice for delayers of first birth.

Abstract Background The effectiveness of malaria prevention with long-lasting insecticidal nets and indoor residual spraying is limited by emerging insecticide resistance, evasive mosquito behaviours that include outdoor biting, sub-optimal implementation and inappropriate use. New vector control interventions are required and their potential effectiveness will be enhanced if existing household perceptions and practices are integrated into intervention design. Methods This qualitative descriptive study used focus groups discussions, in-depth interviews and photovoice methods to explore mosquito control perceptions and practices among residents in four study sites in Dar es Salaam, Tanzania. Results Mosquitoes were perceived as a growing problem, directly attributed to widespread environmental deterioration and lack of effective mosquito control interventions. Malaria and nuisance biting were perceived as the main problem caused by mosquitoes. Breeding sites were clearly distinguished from resting sites but residents did not differentiate between habitats producing malaria vector mosquitoes and others producing mostly nuisance mosquitoes. The most frequently mentioned protection methods in the wealthiest locations were bed nets, aerosol insecticide sprays, window screens, and fumigation, while bed nets were most frequently mentioned and described as ‘part of the culture’ in the least wealthy locations. Mosquito-proofed housing was consistently viewed as desirable, but considered unaffordable outside wealthiest locations. Slapping and covering up with clothing were most commonly used to prevent biting outdoors. Despite their utility outdoors, topical repellents applied to the skin were considered expensive, and viewed with suspicion due to perceived side effects. Improving the local environment was the preferred method for preventing outdoor biting. Affordability, effectiveness, availability, practicality, as well as social influences, such as government recommendations, socialization and internalization (familiarization and habit) were described as key factors influencing uptake. Conclusions Outdoor transmission is widely accepted as an obstacle to malaria elimination. Larval source management, targeting both malaria vectors and nuisance-biting mosquitoes, is the preferred method for mosquito control among the residents of Dar es Salaam and should be prioritized for development alongside new methods for outdoor personal protection. Even if made available, effective and affordable, these additional interventions may require time and user experience to achieve positive reputations and trustworthiness.

Facilitating mutually-beneficial educational activities between researchers and school students is an increasingly popular way for research institutes to engage with communities who host health research, but these activities have rarely been formally examined as a community or public engagement approach in health research. The KEMRI-Wellcome Trust Research Programme (KWTRP) in Kilifi, Kenya, through a Participatory Action Research (PAR) approach involving students, teachers, researchers and education stakeholders, has incorporated ‘school engagement’ as a key component into their community engagement (CE) strategy. School engagement activities at KWTRP aim at strengthening the ethical practice of the institution in two ways: through promoting an interest in science and research among school students as a form of benefit-sharing; and through creating forums for dialogue aimed at promoting mutual understanding between researchers and school students. In this article, we provide a background of CE in Kilifi and describe the diverse ways in which health researchers have engaged with communities and schools in different parts of the world. We then describe the way in which the KWTRP school engagement programme (SEP) was developed and scaled-up. We conclude with a discussion about the challenges, benefits and lessons learnt from the SEP implementation and scale-up in Kilifi, which can inform the establishment of SEPs in other settings.

Abstract Background Nutrition plays an important role in child survival and development. Treatment action in the management of child health and nutrition is influenced by perceptions of illness, and gender plays an important role. However, little is known about if and how moderate undernutrition is recognised among lay populations, or how local social norms and intra-household dynamics affect decisions to seek biomedical assistance for nutritional concerns. In this paper we describe how childhood nutritional problems are recognised and understood within rural households. We demonstrate how context influences local constructs of ‘normal’, and suggest the centrality of gender in the management of child health and nutrition in our research context. Methods This qualitative study was undertaken in Kilifi County on the Kenyan Coast. A set of 15 households whose children were engaged in a community-based nutrition intervention were followed up over a period of twelve months. Over a total of 54 household visits, group and individual in-depth interviews were conducted with a range of respondents, supplemented by non-participant observations. Eight in-depth interviews with community representatives were also conducted. Results Local taxonomies of childhood undernutrition were found to overlap with, but differ from, biomedical categories. In particular, moderate undernutrition was generally not recognised as a health problem requiring treatment action, but rather as routine and manageable, typically seasonal, weight-loss. Where symptoms were considered more serious and requiring remedial action, household management strategies were typically based on perceived aetiology of the illness. Additionally, gender emerged as a potentially central theme in childhood nutrition problems and related management. Women reported that they have primary responsibility for ensuring children’s good health and nutritional status, and that they are often held accountable when their children are of sub-optimal health. Conclusion Perceptions of child nutrition and illness and gendered roles within households influence treatment action, and engagement with nutrition interventions. Community-based nutrition interventions must recognise these complex realities.

To successfully eliminate human African trypanosomiasis (HAT), healthcare workers (HCWs) must maintain their diagnostic acuity to identify cases as the disease becomes rarer. HAT experts refer to this concept as a ‘reflex’ which incorporates the idea that diagnostic expertise, particularly skills involved in recognising which patients should be tested, comes from embodied knowledge, accrued through practice. We investigated diagnostic pathways in the detection of 32 symptomatic HAT patients in South Sudan and found that this ‘reflex’ was not confined to HCWs. Indeed, lay people suggested patients test for HAT in more than half of cases using similar practices to HCWs, highlighting the importance of the expertise present in disease-affected communities. Three typologies of diagnostic practice characterised patients’ detection: ‘syndromic suspicion’, which closely resembled the idea of an expert diagnostic reflex, as well as ‘pragmatic testing’ and ‘serendipitous detection’, which depended on diagnostic expertise embedded in hospital and lay social structures when HAT-specific suspicion was ambivalent or even absent. As we approach elimination, health systems should embrace both expert and non-expert forms of diagnostic practice that can lead to detection. Supporting multidimensional access to HAT tests will be vital for HCWs and lay people to practice diagnosis and develop their expertise.

Introduction Every year ~800,000 people die by suicide worldwide. The pathway to suicide is mediated by highly complex processes, integrating a large number of risk factor variables which are extensively dependent on one another. Unfortunately, suicide risk prediction has been a challenging problem for epidemiological studies and their application to practice. Objectives and Approach We aim at exploring the feasibility of using artificial neural networks (ANNs) based on routinely collected electronic health records (EHRs) to support the identification of those at high risk of suicide when in contact with health services. We used the Secure Anonymised Information Linkage Databank UK to extract those who died by suicide between 2001 and 2015 and identify controls. We extracted risk factors from primary and secondary care about mental health, injury, substance misuse, maltreatment, sleep disorders and prescriptions. We trained a simple ANN to differentiate between cases/controls to test the feasibility of this approach. Results A total of 2,604 suicide cases and 20 paired controls per case were used during 10x10 K-Fold repeated cross-validation. We obtained an error rate of 26.78% ± 1.46 differentiating between cases and controls. The distribution of controls was concentrated around estimated risks" Conclusion/Implications The proposed method performed similar to other works based on specialized questionnaire data. Prescription of psychotropics, depression and anxiety, and self-harm were strongly linked with higher risks, followed by hospital admission and substance misuse. This is in keeping with known literature, providing evidence that the proposed approach is feasible.

BACKGROUND:Intermittent preventive treatment for malaria in pregnancy (IPTp) is part of a multi-pronged strategy aimed at preventing malaria in pregnancy in areas of moderate to high transmission in sub-Saharan Africa. Despite being formally adopted as a malaria prevention policy over a decade ago, IPTp coverage has remained low. Recent demands for action have incorporated calls to strengthen IPTp monitoring and evaluation systems, including the use of routine data, to measure coverage, track implementation and identify roadblocks to improving uptake. Concerns about the quality of malaria indicators reported through routine information systems are well recognized, but there are few data on the realities of IPTp recording practices in frontline facilities or their entry into District Health Information Software (DHIS2). METHODS:Drawing on fieldwork conducted in two malaria endemic sub-counties in Kenya, we explore how local adaptations and innovations employed by health workers and sub-country managers to cope with a range of health system constraints, shape recording practices and in turn, the measurement of IPTp. Data were collected through observations, interviews, and document reviews. Data analysis and interpretation was guided by thematic analysis approach. RESULTS:Measurement of IPTp was undermined by health system constraints such as stock-out of drugs and human resource shortages. Coping strategies adopted by health workers to address these challenges ensured continuity in service delivery and IPTp data generation but had variable consequences on IPTp data quality. Unclear recording and reporting instructions also led to lack of standardization in IPTp data generation. The use of redundant tools created significant data burdens which undermined service delivery in general. CONCLUSIONS:There is need to integrate monthly reporting forms so as to remove redundancies which exacerbates workload for health workers and disrupts service delivery. Similarly, data collection instructions in registers and reporting forms need to be clarified to standardize IPTp data generation across health facilities. There is also need to address broader contextual factors such as stock-out of commodities and human resource shortages which undermine IPTp data generation process.

BackgroundAccess to prompt and effective treatment is the cornerstone for malaria control. Population Services International in collaboration with the Ministry of Health launched a malaria behaviour change communication intervention in Nyanza province, Kenya. The initiative aimed to improve: symptom recognition and prompt access to government health facilities for febrile children; effective treatment with the recommended first-line drug artemether-lumefantrine (AL) in public health facilities and adherence to the AL regimen.MethodsPre- and post-intervention cross-sectional household surveys were used to evaluate the impact of the intervention on prompt and correct use of AL for febrile children below five years of age. The primary outcome was the proportion of children below five years of age with fever in the last 14 days accessing AL within 48 hours of fever onset.ResultsThere was an increase from 62.8% pre-intervention to 79.4% post-intervention (95% CI: 11.1, 22.1) in caregivers who reported seeking formal treatment promptly (on the same day, or next day) for their febrile children. However, there was a decrease in the use of government health facilities in the post-intervention period. There was a small increase in the proportion of children accessing AL within 48 hours of fever onset [18.4% vs 23.5% (0.1-10.0)].ConclusionThe findings of this evaluation demonstrate that interventions that target only one sector may have a limited impact on improvements in prompt and effective treatment where multiple sources of treatments are sought for febrile illness. Additionally, the context in which an intervention is implemented is likely to influence the process and outcomes.

Clinical trials conducted in Africa often require substantial investments to support trial centres and public health facilities. Trial resources could potentially generate benefits for routine health service delivery but may have unintended consequences. Strengthening ethical practice requires understanding the potential effects of trial inputs on the perceptions and practices of routine health care providers. This study explores the influence of malaria vaccine trials on health service delivery in Ghana, Kenya and Burkina Faso.We conducted: audits of trial inputs in 10 trial facilities and among 144 health workers; individual interviews with frontline providers (n=99) and health managers (n=14); and group discussions with fieldworkers (n=9 discussions). Descriptive summaries were generated from audit data. Qualitative data were analysed using a framework approach.Facilities involved in trials benefited from infrastructure and equipment upgrades, support with essential drugs, access to trial vehicles, and placement of additional qualified trial staff. Qualified trial staff in facilities were often seen as role models by their colleagues; assisting with supportive supervision and reducing facility workload. Some facility staff in place before the trial also received formal training and salary top-ups from the trials. However, differential access to support caused dissatisfaction, and some interviewees expressed concerns about what would happen at the end of the trial once financial and supervisory support was removed.Clinical trials function as short-term complex health service delivery interventions in the facilities in which they are based. They have the potential to both benefit facilities, staff and communities through providing the supportive environment required for improvements in routine care, but they can also generate dissatisfaction, relationship challenges and demoralisation among staff. Minimising trial related harm and maximising benefits requires careful planning and engagement of key actors at the outset of trials, throughout the trial and on its' completion.

Capillary refill time (CRT) is widely recommended as part of the routine assessment of unwell children.To determine the diagnostic value of capillary refill time for a range of serious outcomes in children.We searched Medline, Embase and CINAHL from inception to June 2014. We included studies that measured both capillary refill time and a relevant clinical outcome such as mortality, dehydration, meningitis, or other serious illnesses in children aged up to 18 years of age. We screened 1,265 references, of which 24 papers were included in this review. Where sufficient studies were available, we conducted meta-analysis and constructed hierarchical summary ROC curves.Meta-analysis on the relationship between capillary refill time and mortality resulted in sensitivity of 34.6% (95% CI 23.9 to 47.1%), specificity 92.3% (88.6 to 94.8%), positive likelihood ratio 4.49 (3.06 to 6.57), and negative likelihood ratio 0.71 (0.60 to 0.84). Studies of children attending Emergency Departments with vomiting and diarrhea showed that capillary refill time had specificity of 89 to 94% for identifying 5% dehydration, but sensitivity ranged from 0 to 94%. This level of heterogeneity precluded formal meta-analysis of this outcome. Meta-analysis was not possible for other outcomes due to insufficient data, but we found consistently high specificity for a range of outcomes including meningitis, sepsis, admission to hospital, hypoxia, severity of illness and dengue.Our results show that capillary refill time is a specific sign, indicating that it can be used as a "red-flag": children with prolonged capillary refill time have a four-fold risk of dying compared to children with normal capillary refill time. The low sensitivity means that a normal capillary refill time should not reassure clinicians.

Antenatal ultrasound suits developing countries by virtue of its versatility, relatively low cost and safety, but little is known about women's or local provider's perspectives of this upcoming technology in such settings. This study was undertaken to better understand how routine obstetric ultrasound is experienced in a displaced Burmese population and identify barriers to its acceptance by local patients and providers.Qualitative (30 observations, 19 interviews, seven focus group discussions) and quantitative methods (questionnaire survey with 644 pregnant women) were used to provide a comprehensive understanding along four major themes: safety, emotions, information and communication, and unintended consequences of antenatal ultrasound in refugee and migrant clinics on the Thai Burmese border. One of the main concerns expressed by women was the danger of childbirth which they mainly attributed to fetal malposition. Both providers and patients recognized ultrasound as a technology improving the safety of pregnancy and delivery. A minority of patients experienced transitory shyness or anxiety before the ultrasound, but reported that these feelings could be ameliorated with improved patient information and staff communication. Unintended consequences of overuse and gender selective abortions in this population were not common.The results of this study are being used to improve local practice and allow development of explanatory materials for this population with low literacy. We strongly encourage facilities introducing new technology in resource poor settings to assess acceptability through similar inquiry.

BackgroundThe currently recommended approach for preventing malaria in pregnancy (MiP), intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPT), has been questioned due to the spread of resistance to SP. Whilst trials are underway to test the efficacy of future alternative approaches, it is important to start exploring the feasibility of their implementation.Methods and findingsThis study uses a discrete choice experiment (DCE) method to assess the potential resistance of health workers to changing strategies for control of MiP. In Ashanti region in Ghana, 133 antenatal clinic health workers were presented with 16 choice sets of two alternative policy options, each consisting of a bundle of six attributes representing certain clinical guidelines for controlling MiP (type of approach and drug used), possible associated maternal and neo-natal outcomes, workload and financial incentives. The data were analysed using a random effects logit model. Overall, staff showed a preference for a curative approach with pregnant women tested for malaria parasites and treated only if positive, compared to a preventive approach (OR 1.6; p = 0.001). Increasing the incidence of low birth weight or severe anaemia by 1% would reduce the odds of preferring an approach by 18% and 10% respectively. Midwives were more resistant to potential changes to current guidelines than lower-level cadres.ConclusionsIn Ashanti Region, resistance to change by antenatal clinic workers from a policy of SP-IPT to IST would generally be low, and it would disappear amongst midwives if health outcomes for the mother and baby were improved by the new strategy. DCEs are a promising approach to identifying factors that will increase the likelihood of effective implementation of new interventions immediately after their efficacy has been proven.

Malaria in pregnancy (MiP) is associated with increased risks of maternal and foetal complications. The WHO recommends a package of interventions including intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), insecticide-treated nets and effective case management. However, with increasing SP resistance, the effectiveness of SP-IPT has been questioned. Intermittent screening and treatment (IST) has recently been shown in Ghana to be as efficacious as SP-IPT. This study investigates two important requirements for effective delivery of IST and SP-IPT: antenatal care (ANC) provider knowledge, and acceptance of the different strategies. Structured interviews with 134 ANC providers at 67 public health facilities in Ashanti Region, Ghana collected information on knowledge of the risks and preventative and curative interventions against MiP. Composite indicators of knowledge of SP-IPT, and case management of MiP were developed. Log binomial regression of predictors of provider knowledge was explored. Qualitative data were collected through in-depth interviews with fourteen ANC providers with some knowledge of IST to gain an indication of the factors influencing acceptance of the IST approach. 88.1% of providers knew all elements of the SP-IPT policy, compared to 20.1% and 41.8% who knew the treatment policy for malaria in the first or second/third trimesters, respectively. Workshop attendance was a univariate predictor of each knowledge indicator. Qualitative findings suggest preference for prevention over cure, and increased workload may be barriers to IST implementation. However, a change in strategy in the face of SP resistance is likely to be supported; health of pregnant women is a strong motivation for ANC provider practice. If IST was to be introduced as part of routine ANC activities, attention would need to be given to improving the knowledge and practices of ANC staff in relation to appropriate treatment of MiP. Health worker support for any MiP intervention delivered through ANC clinics is critical.