Embedded implementation research in programming at scale - the new normal to be!

If you want to run faster, don't just buy a new pair of shoes; also consider your training methods and where you run.This supplement examines six countries that have run faster than others in reducing under-five mortality, taking an implementation research approach, with country case studies done with local researchers and local institutions. Key generalizable learnings are to choose and adapt implementation strategies to context, design strategies to target the most vulnerable, systematically learn from implementation experience, and to leverage non-health-sector contributions.Embedding implementation research in programming has the potential to greatly improve and accelerate the contextualization and implementation of evidence-based child survival interventions to improve equity in coverage and overall effectiveness in reducing under-five mortality. It is now time to build such capacity in local institutions at scale, and incentives for concerned stakeholders to make this the new normal. Regional institutions should now take the lead in making this happen, not just in individual institutions and countries, but across entire regions, supported by global partners.Trial registration N/A.

Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid.

Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide. This nucleotide change resulted in amino acid substitution F514I in the viral capsid, which led to >10,000-fold higher replication in systemic organs including the brain. Pathogenicity was mediated by enhanced recruitment and infection of intestinal myeloid cells and increased extraintestinal dissemination of virus. Interestingly, the trade-off for this mutation was reduced fitness in an IFN-competent host, in which CR6 bearing F514I exhibited decreased intestinal replication and shedding. In an immunodeficient context, a spontaneous amino acid change can thus convert a relatively avirulent viral strain into a lethal pathogen.

Disruption of Type III Interferon (IFN) Genes Ifnl2 and Ifnl3 Recapitulates Loss of the Type III IFN Receptor in the Mucosal Antiviral Response.

Type III interferon (IFN), or IFN lambda (IFN-λ), is an essential component of the innate immune response to mucosal viral infections. In both the intestine and the lung, signaling via the IFN-λ receptor (IFNLR) controls clinically important viral pathogens, including influenza virus, norovirus, and rotavirus. While it is thought that IFN-λ cytokines are the exclusive ligands for signaling through IFNLR, it is not known whether genetic ablation of these cytokines phenotypically recapitulates disruption of the receptor. Here, we report the serendipitous establishment of Ifnl2-/- Ifnl3-/- mice, which lack all known functional murine IFN-λ cytokines. We demonstrate that, like Ifnlr1-/- mice lacking IFNLR signaling, these mice display defective control of murine norovirus, reovirus, and influenza virus and therefore genocopy Ifnlr1-/- mice. Thus, for regulation of viral infections at mucosal sites of both the intestine and lung, signaling via IFNLR can be fully explained by the activity of known cytokines IFN-λ2 and IFN-λ3. Our results confirm the current understanding of ligand-receptor interactions for type III IFN signaling and highlight the importance of this pathway in regulation of mucosal viral pathogens.IMPORTANCE Type III interferons are potent antiviral cytokines important for regulation of viruses that infect at mucosal surfaces. Studies using mice lacking the Ifnlr1 gene encoding the type III interferon receptor have demonstrated that signaling through this receptor is critical for protection against influenza virus, norovirus, and reovirus. Using a genetic approach to disrupt murine type III interferon cytokine genes Ifnl2 and Ifnl3, we found that mice lacking these cytokines fully recapitulate the impaired control of viruses observed in mice lacking Ifnlr1 Our results support the idea of an exclusive role for known type III interferon cytokines in signaling via IFNLR to mediate antiviral effects at mucosal surfaces. These findings emphasize the importance of type III interferons in regulation of a variety of viral pathogens and provide important genetic evidence to support our understanding of the ligand-receptor interactions in this pathway.

Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis.

BACKGROUND: Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD). We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD. METHODS: This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation. Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV1] or worsening St George's Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models. RESULTS: The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69-84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM. All components contributed to the CID event rate. Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events. The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count. CONCLUSIONS: Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients' eosinophil levels. CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development.

Primary health care and nutrition.

Globally, dietary factors are responsible for about one in five deaths. In many low- and middle-income countries different forms of malnutrition (including obesity and undernutrition) can co-exist within the same population. This double burden of malnutrition is placing a disproportional strain on health systems, slowing progress towards universal health coverage (UHC). Poor nutrition also impedes the growth of local economies, ultimately affecting the global economy. In this article, we argue that comprehensive primary health care should be used as a platform to address the double burden of malnutrition. We use a conceptual framework based on human rights and the Astana Declaration on primary health care to examine existing recommendations and propose guidance on how policy-makers and providers of community-oriented primary health care can strengthen the role of nutrition within the UHC agenda. Specifically, we propose four thematic areas for action: (i) bridging narratives and strengthening links between the primary health care and the nutrition agenda with nutrition as a human rights issue; (ii) encouraging primary health-care providers to support local multisectoral action on nutrition; (iii) empowering communities and patients to address unhealthy diets; and (iv) ensuring the delivery of high-quality promotive, preventive, curative and rehabilitative nutrition interventions. For each theme we summarize the available strategies, policies and interventions that can be used by primary health-care providers and policy-makers to strengthen nutrition in primary health care and thus the UHC agenda.

Environ un décès sur cinq dans le monde est dû à des facteurs alimentaires. Dans de nombreux pays à faible et moyen revenu, différentes formes de malnutrition (y compris l'obésité et la dénutrition) peuvent coexister au sein d'une même population. Ce double fardeau de malnutrition exerce une pression démesurée sur les systèmes de santé, ralentissant la progression vers une couverture maladie universelle (CMU). Une mauvaise alimentation entrave également la croissance des économies locales, ce qui en fin de compte affecte l'économie mondiale. Dans cet article, nous estimons qu'il est impératif d'utiliser une approche globale des soins de santé primaires comme plateforme pour s'attaquer au double fardeau de la malnutrition. Nous avons employé un cadre conceptuel fondé sur les droits humains et la Déclaration d'Astana sur les soins de santé primaires. D'une part pour examiner les recommandations existantes, et d'autre part pour fournir un éclairage sur la manière dont les législateurs et les prestataires de soins de santé primaires, implantés au niveau communautaire, peuvent renforcer le rôle de la nutrition dans le programme de CMU. Nous proposons plus exactement quatre champs d'action : (i) aligner les discours et consolider les liens entre les soins de santé primaires et le programme de nutrition, en intégrant ce dernier dans la thématique des droits humains; (ii) encourager les prestataires de soins de santé primaires à soutenir les initiatives locales multisectorielles portant sur la nutrition; (iii) donner aux patients et aux collectivités le pouvoir de lutter contre l'alimentation déséquilibrée; et enfin, (iv) assurer la mise en œuvre d'interventions de qualité pour la promotion, la prévention, le traitement et la réhabilitation en matière de nutrition. Pour chaque champ d'action, nous résumons les stratégies, politiques et interventions à la disposition des législateurs et prestataires de soins de santé primaires pour renforcer le rôle de la nutrition dans les soins de santé primaires et, par conséquent, le programme de CMU.

Los factores alimentarios son responsables de aproximadamente una de cada cinco muertes en todo el mundo. Diferentes tipos de malnutrición (incluidas la obesidad y la desnutrición) pueden coexistir en la misma población de muchos países de ingresos bajos y medios. Esta doble carga de la malnutrición está ejerciendo una presión desproporcionada sobre los sistemas sanitarios, lo que ralentiza los progresos hacia la cobertura sanitaria universal (CSU). Además, la mala nutrición dificulta el crecimiento de las economías locales, lo que en última instancia afecta a la economía global. En este artículo, se argumenta que la atención primaria de salud integral se debería utilizar como plataforma para abordar la doble carga de la malnutrición. Se utiliza un marco conceptual basado en los derechos humanos y en la Declaración de Astaná sobre la atención primaria de salud para analizar las recomendaciones existentes y proponer directrices sobre cómo los responsables de formular las políticas y los proveedores de atención primaria de salud orientada a la comunidad pueden fortalecer la función de la nutrición dentro del programa de la CSU. En concreto, se proponen cuatro áreas temáticas de acción: (i) narrativas de vinculación y fortalecimiento de los vínculos entre la atención primaria de salud y el programa de nutrición en donde la nutrición sea una cuestión de derechos humanos; (ii) alentar a los proveedores de atención primaria de salud a que apoyen la medida multisectorial local sobre la nutrición; (iii) potenciar a las comunidades y a los pacientes para tratar las dietas poco saludables; y (iv) garantizar la realización de intervenciones de nutrición de alta calidad de tipo promocional, preventivo, curativo y de rehabilitación. Para cada tema se resumen las estrategias, políticas e intervenciones disponibles que los proveedores de atención primaria de salud y los responsables de formular las políticas pueden utilizar para fortalecer la nutrición en la atención primaria de salud y, por consiguiente, el programa de la CSU.

Peer supervision experiences of drug sellers in a rural district in East-Central Uganda: a qualitative study.

BACKGROUND: Support supervision improves performance outcomes among health workers. However, the national professional guidelines for new licenses and renewal for Class C drug shops in Uganda prescribe self-supervision of licensed private drug sellers. Without support supervision, inappropriate treatment of malaria, pneumonia and diarrhoea among children under 5 years of age continues unabated. This study assessed experiences of drug sellers and peer supervisors at the end of a peer supervision intervention in Luuka District in East Central Uganda. METHODS: Eight in-depth interviews (IDIs) were held with peer supervisors while five focus group discussions (FGDs) were conducted among registered drug sellers at the end of the peer supervision intervention. The study assessed experiences and challenges of peer supervisors and drug sellers regarding peer supervision. Transcripts were imported into Atlas.ti 7 qualitative data management software where they were analysed using thematic content analysis. RESULTS: Initially, peer supervisors were disliked and regarded by drug sellers as another extension of drug inspectors. However, with time a good relationship was established between drug sellers and peer supervisors leading to regular, predictable and supportive peer supervision. This increased confidence of drug sellers in using respiratory timers and rapid diagnostic tests in diagnosing pneumonia symptoms and uncomplicated malaria, respectively, among children under 5 years. There was also an improvement in completing the sick child register which was used for self-assessment by drug sellers. The drug shop association was mentioned as a place where peer supervision should be anchored since it was a one-stop centre for sharing experiences and continuous professional development. Drug sellers proposed including community health workers in monthly drug shop association meetings so that they may also gain from the associated benefits. Untimely completion of the sick child registers by drug sellers and inadequate financial resources were the main peer supervision challenges mentioned. CONCLUSION: Drug sellers benefitted from peer supervision by developing a good relationship with peer supervisors. This relationship guaranteed reliable and predictable supervision ultimately leading to improved treatment practices. There is need to explore the minimum resources needed for peer supervision of drug sellers to further inform practice and policy.

Disease mapping of early- and late-stage cancer to monitor inequalities in early detection: a study of cutaneous malignant melanoma.

We consider disease mapping of early- and late-stage cancer, in order to identify and monitor inequalities in early detection. Our method is demonstrated by mapping cancer incidence at high geographical resolution using data on 10,302 cutaneous malignant melanoma (CMM) cases within the 3.7 million population of South-West Sweden. The cases were geocoded into small-areas, each with a population size between 600 and 2600 and accessible socio-demographic data. Using the disease mapping application Rapid Inquiry Facility (RIF) 4.0, we produced regional maps to visualise spatial variations in stage I, II and III-IV CMM incidences, complemented by local maps to explore the variations within two urban areas. Pronounced spatial disparities in stage I CMM incidence were revealed by the regional and local maps. Stage I CMM incidence was markedly higher in wealthier small-areas, in particular within each urban area. A twofold higher stage I incidence was observed, on average, in the wealthiest small-areas (upper quintile) than in the poorest small-areas (lower quintile). We identified in the regional map of stage III-IV CMM two clusters of higher or lower than expected late-stage incidences which were quite distinct from those identified for stage I. In conclusion, our analysis of CMM incidences supported the use of this method of cancer stage incidence mapping for revealing geographical and socio-demographic disparities in cancer detection.

Impairments, functional limitations, and access to services and education for children with cerebral palsy in Uganda: a population-based study.

AIM: To describe the functional limitations and associated impairments of children with cerebral palsy (CP) in rural Uganda, and care-seeking behaviour and access to assistive devices and education. METHOD: Ninety-seven children with CP (42 females, 55 males; age range 2-17y) were identified in a three-stage population-based screening with subsequent medical examinations and functional assessments. Information on school and access to care was collected using questionnaires. The data were compared with Swedish and Australian cohorts of children with CP. We used the χ2 test and linear regression models to analyse differences between groups. RESULTS: Younger children were more severely impaired than older children. Two-fifths of the children had severe impairments in communication, about half had intellectual disability, and one third had seizures. Of 37 non-walking children, three had wheelchairs and none had walkers. No children had assistive devices for hearing, seeing, or communication. Care-seeking was low relating to lack of knowledge, insufficient finances, and 'lost hope'. One-third of the children attended school. Ugandan children exhibited lower developmental trajectories of mobility and self-care than a Swedish cohort. INTERPRETATION: The needs for children with CP in rural Uganda are not met, illustrated by low care-seeking, low access to assistive devices, and low school attendance. A lack of rehabilitation and stimulation probably contribute to the poor development of mobility and self-care skills. There is a need to develop and enhance locally available and affordable interventions for children with CP in Uganda. WHAT THIS PAPER ADDS: Development of mobility and self-care skills is lower in Ugandan than Swedish children with cerebral palsy (CP). Older children in Uganda with CP are less impaired than younger children. Untreated seizures and impairments of communication and intellect are common. Access to health services, assistive devices, and education is low. Caregivers lack knowledge and finances to seek care and often lose hope of their child improving.

Bypassing or successful referral? A population-based study of reasons why women travel far for childbirth in Eastern Uganda.

BACKGROUND: Delivery in a facility with a skilled health provider is considered the most important intervention to reduce maternal and early newborn deaths. Providing care close to people's homes is an important strategy to facilitate equitable access, but many women are known to bypass the closest delivery facility for a higher level one. The aim of this study was to investigate to what extent mothers in rural Uganda bypassed their nearest facility for childbirth care and the determinants for their choice. METHODS: The study used data collected as part of the Expanded Quality Management Using Information power (EQUIP) study in the Mayuge District of Eastern Uganda between 2011 and 2014. In this study, bypassing was defined as delivering in a health facility that was not the nearest childbirth facility to the mother's home. Multilevel logistic regression was used to model the relationship between bypassing the nearest health facility for childbirth and the different independent factors. RESULTS: Of all women delivering in a health facility, 45% (499/1115) did not deliver in the nearest facility regardless of the level of care. Further, after excluding women who delivered in health centre II (which is not formally equipped to provide childbirth care) and excluding those who were referred or had a caesarean section (because their reasons for bypassing may be different), 29% (204/717) of women bypassed their nearest facility to give birth in another facility, 50% going to the only hospital of the district. The odds of bypassing increased if a mother belonged to highest wealth quintile compared to the lowest quintile (AOR 2.24, 95% CI: 1.12-4.46) and decreased with increase of readiness of score of the nearest facility for childbirth (AOR = 0.84, 95% CI: 0.69-0.99). CONCLUSIONS: The extent of bypassing the nearest childbirth facility in this rural Ugandan setting was 29%, and was associated primarily with the readiness of the nearest facility to provide care as well as the wealth of the household. These results suggest inequalities in bypassing for better quality care that have important implications for improving Uganda's maternal and newborn health outcomes.

'I know those people will be approachable and not mistreat us': a qualitative study of inspectors and private drug sellers' views on peer supervision in rural Uganda.

BACKGROUND: Peer supervision improves health care delivery by health workers. However, in rural Uganda, self-supervision is what is prescribed for licensed private drug sellers by statutory guidelines. Evidence shows that self-supervision encourages inappropriate treatment of children less than 5 years of age by private drug sellers. This study constructed a model for an appropriate peer supervisor to augment the self-supervision currently practiced by drug sellers at district level in rural Uganda. METHODS: In this qualitative study, six Key informant interviews were held with inspectors while ten focus group discussions were conducted with 130 drug sellers. Data analysis was informed by the Kathy Charmaz constructive approach to grounded theory. Atlas ti.7 software package was used for data management. RESULTS: A model with four dimensions defining an appropriate peer supervisor was developed. The dimensions included; incentives, clearly defined roles, mediation and role model peer supervisor. While all dimensions were regarded as being important, all participants interviewed agreed that incentives for peer supervisors were the most crucial. Overall, an appropriate peer supervisor was described as being exemplary to other drug sellers, operated within a defined framework, well facilitated to do their role and a good go-between drug sellers and government inspectors. CONCLUSION: Four central contributions advance literature by the model developed by our study. First, the model fills a supervision gap for rural private drug sellers. Second, it highlights the need for terms of reference for peer supervisors. Third, it describes who an appropriate peer supervisor should be. Lastly, it elucidates the kind of resources needed for peer supervision.

HOIL1 Is Essential for the Induction of Type I and III Interferons by MDA5 and Regulates Persistent Murine Norovirus Infection.

The linear ubiquitin chain assembly complex (LUBAC), composed of heme-oxidized IRP2 ubiquitin ligase 1 (HOIL1), HOIL1-interacting protein (HOIP), and SHANK-associated RH domain-interacting protein (SHARPIN), is a crucial regulator of multiple immune signaling pathways. In humans, HOIL1 or HOIP deficiency is associated with an immune disorder involving autoinflammation, immunodeficiency, and inflammatory bowel disease (IBD)-like symptoms. During viral infection, LUBAC is reported to inhibit the induction of interferon (IFN) by the cytosolic RNA sensor retinoic acid-inducible gene I (RIG-I). Surprisingly, we found that HOIL1 is essential for the induction of both type I and type III IFNs, as well as the phosphorylation of IFN regulatory factor 3 (IRF3), during murine norovirus (MNoV) infection in cultured dendritic cells. The RIG-I-like receptor, melanoma differentiation-associated protein 5 (MDA5), is also required for IFN induction and IRF3 phosphorylation during MNoV infection. Furthermore, HOIL1 and MDA5 were required for IFN induction after Theiler's murine encephalomyelitis virus infection and poly(I·C) transfection, but not Sendai virus or vesicular stomatitis virus infection, indicating that HOIL1 and LUBAC are required selectively for MDA5 signaling. Moreover, Hoil1-/- mice exhibited defective control of acute and persistent murine norovirus infection and defective regulation of MNoV persistence by the microbiome as also observed previously for mice deficient in interferon lambda (IFN-λ) receptor, signal transducer and activator of transcription factor 1 (STAT1), and IRF3. These data indicate that LUBAC plays a critical role in IFN induction to control RNA viruses sensed by MDA5.IMPORTANCE Human noroviruses are a leading cause of gastroenteritis throughout the world but are challenging to study in vivo and in vitro Murine norovirus (MNoV) provides a tractable genetic and small-animal model to study norovirus biology and immune responses. Interferons are critical mediators of antiviral immunity, but excessive expression can dysregulate the immune system. IFN-λ plays an important role at mucosal surfaces, including the gastrointestinal tract, and both IFN-λ and commensal enteric bacteria are important modulators of persistent MNoV infection. LUBAC, of which HOIL1 is a component, is reported to inhibit type I IFN induction after RIG-I stimulation. We show, in contrast, that HOIL1 is critical for type I and III IFN induction during infection with MNoV, a virus that preferentially activates MDA5. Moreover, HOIL1 regulates MNoV infection in vivo These data reveal distinct functions for LUBAC in these closely related signaling pathways and in modulation of IFN expression.

Dietary patterns and practices in rural eastern Uganda: Implications for prevention and management of type 2 diabetes.

BACKGROUND: The burden of type 2 diabetes in Sub-Saharan Africa is projected to double by 2040, partly attributable to rapidly changing diets. In this paper, we analysed how community members in rural Uganda understood the concept of a healthy or unhealthy diet, food preparation and serving practices to inform the process of facilitating knowledge and skill necessary for self-management and care for type 2 diabetes. This was a qualitative study involving 20 focus group discussions and eight in-depth interviews among those at risk, patients with type 2 diabetes and the general community members without diabetes mellitus. Data was coded and entered into Atlas ti version 7.5.12 and interpreted using thematic analysis. We identified three main themes, which revealed, the perceptions on food and diet concerning health; the social dimensions of food and influence on diet practices; and food as a gendered activity. Participants noted that eating and cooking practices resulted in unhealthy diets. Their practices were affected by beliefs, poverty and food insecurity. Women determined which foods to prepare, but men prepared only some of the foods such as delicacies like a rice dish "pilau." New commercial and processed foods were increasingly available and consumed even in rural areas. Participants linked signs and symptoms of illness to diet as they narrated changes from past to current food preparation behaviours. Their view of overweight and obesity was also gendered and linked to social status. Participants' perception of disease influenced by diet was similar among those with and without type 2 diabetes, and those at risk. People described what is a healthy diet was as recommended by the health workers, but stated that their practices differed greatly from their knowledge. There was high awareness about healthy and balanced diets, but food is entrenched within social and gendered paradigms, which are slowly changing. Social and gender dimensions of food will need to be addressed through interventions in communities to promote change on a society level.

Decision-making in district health planning in Uganda: does use of district-specific evidence matter?

BACKGROUND: In a decentralised health system, district health managers are tasked with planning for health service delivery, which should be evidence based. However, planning in low-income countries such as Uganda has been described as ad hoc. A systematic approach to the planning process using district-specific evidence was introduced to district health managers in Uganda. However, little is known about how the use of district-specific evidence informs the planning process. In this study, we investigate how the use of this evidence affects decision-making in the planning process and how stakeholders in the planning process perceived the use of evidence. METHODS: A convergent parallel mixed-methods study design was used, where quantitative data was collected from district health annual work plans for the financial years 2012/2013, 2013/2014, 2014/2015 and 2015/2016 as well as from bottleneck analysis reports for 2012, 2013, 2014 and 2015. Qualitative data was collected through semi-structured interviews with key informants from the two study districts. RESULTS: District managers reported that they were able to produce more robust district annual work plans when they used the systematic approach of using district-specific evidence. Approximately half of the prioritised activities in the annual work plans were evidence based. Procurement and logistics, training, and support supervision activities were the most prioritised activities. Between 4% and 5.5% of the total planned expenditure was for child survival, of which 47% to 94% was from donor and other partner contributions. CONCLUSION: District-specific evidence and a structured process for its use to prioritise activities and make decisions in the planning process at the district level helped systematise the planning process. However, the reported limited decision and fiscal space, inadequate funding and high dependency on donor funding did not always allow for the use of district-specific evidence in the planning process.

Can malaria rapid diagnostic tests by drug sellers under field conditions classify children 5 years old or less with or without Plasmodium falciparum malaria? Comparison with nested PCR analysis.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) available as dipsticks or strips, are simple to perform, easily interpretable and do not require electricity nor infrastructural investment. Correct interpretation of and compliance with the RDT results is a challenge to drug sellers. Thus, drug seller interpretation of RDT strips was compared with laboratory scientist re-reading, and PCR analysis of Plasmodium DNA extracted from RDT nitrocellulose strips and fast transient analysis (FTA) cards. Malaria RDT cassettes were also assessed as a potential source of Plasmodium DNA. METHODS: A total of 212 children aged between 2 and 60 months, 199 of whom had complete records at two study drug shops in south western Uganda participated in the study. Duplicate 5 µL samples of capillary blood were picked from the 212 children, dispensed onto the sample well of the CareStart™ Pf-HRP2 RDT cassette and a FTA, Whatman™ 3MM filter paper in parallel. The RDT strip was interpreted by the drug seller within 15-20 min, visually re-read centrally by laboratory scientist and from it; Plasmodium DNA was recovered and detected by PCR, and compared with FTA recovered P. falciparum DNA PCR detection. RESULTS: Malaria positive samples were 62/199 (31.2%, 95% CI 24.9, 38.3) by drug seller interpretation of RDT strip, 59/212 (27.8%, 95% CI 22.2, 34.3) by laboratory scientist, 55/212 (25.9%, 95% CI 20.0, 32.6) by RDT nitrocellulose strip PCR and 64/212 (30.2%, 95% CI 24.4, 37.7). The overall agreement between the drug seller interpretation and laboratory scientist re-reading of the RDT strip was 93.0% with kappa value of 0.84 (95% CI 0.75, 0.92). The drug seller compliance with the reported RDT results was 92.5%. The performance of the three diagnostic strategies compared with FTA-PCR as the gold standard had sensitivity between 76.6 and 86.9%, specificity above 90%, positive predictive values ranging from 79.0 to 89.8% and negative predictive values above 90%. CONCLUSION: Drug sellers can use RDTs in field conditions and achieve acceptable accuracy for malaria diagnosis, and they comply with the RDT results. Plasmodium DNA can be recovered from RDT nitrocellulose strips even in the context of drug shops. Future malaria surveillance and diagnostic quality control studies with RDT cassette as a source of Plasmodium DNA are recommended.

Private retail drug shops: what they are, how they operate, and implications for health care delivery in rural Uganda.

BACKGROUND: Retail drug shops play a significant role in managing pediatric fevers in rural areas in Uganda. Targeted interventions to improve drug seller practices require understanding of the retail drug shop market and motivations that influence practices. This study aimed at describing the operational environment in relation to the Uganda National Drug Authority guidelines for setup of drug shops; characteristics, and dispensing practices of private retail drug shops in managing febrile conditions among under-five children in rural western Uganda. METHODS: Cross sectional survey of 74 registered drug shops, observation checklist, and 428 exit interviews using a semi-structured questionnaire with care-seekers of children under five years of age, who sought care at drug shops during the survey period. The survey was conducted in Mbarara and Bushenyi districts, South Western Uganda, in May 2013. RESULTS: Up to 90 and 79% of surveyed drug shops in Mbarara and Bushenyi, largely operate in premises that meet National Drug Authority requirements for operational suitability and ensuring medicines safety and quality. Drug shop attendants had some health or medical related training with 60% in Mbarara and 59% in Bushenyi being nurses or midwives. The rest were clinical officers, pharmacists. The most commonly stocked medicines at drug shops were Paracetamol, Quinine, Cough syrup, ORS/Zinc, Amoxicillin syrup, Septrin® syrup, Artemisinin-based combination therapies, and multivitamins, among others. Decisions on what medicines to stock were influenced by among others: recommended medicines from Ministry of Health, consumer demand, most profitable medicines, and seasonal disease patterns. Dispensing decisions were influenced by: prescriptions presented by client, patients' finances, and patient preferences, among others. Most drug shops surveyed had clinical guidelines, iCCM guidelines, malaria and diarrhea treatment algorithms and charts as recommended by the Ministry of Health. Some drug shops offered additional services such as immunization and sold non-medical goods, as a mechanism for diversification. CONCLUSION: Most drug shops premises adhered to the recommended guidelines. Market factors, including client demand and preferences, pricing and profitability, and seasonality largely influenced dispensing and stocking practices. Improving retail drug shop practices and quality of services, requires designing and implementing both supply-side and demand side strategies.

Integrated community case management by drug sellers influences appropriate treatment of paediatric febrile illness in South Western Uganda: a quasi-experimental study.

BACKGROUND: Fever case management is a major challenge for improved child health globally, despite existence of cheap and effective child survival health technologies. The integrated Community Case Management (iCCM) intervention of paediatric febrile illnesses though adopted by Uganda's Ministry of Health to be implemented by community health workers, has not addressed the inaccess to life-saving medicines and diagnostics. Therefore, the iCCM intervention was implemented in private drug shops and evaluated for its effect on appropriate treatment of paediatric fever in a low malaria transmission setting in South Western Uganda. METHODS: From June 2013 to September 2015, the effect of the iCCM intervention on drug seller paediatric fever management and adherence to iCCM guidelines was assessed in a quasi-experimental study in South Western Uganda. A total of 212 care-seeker exit interviews were done before and 285 after in the intervention arm as compared to 216 before and 268 care-seeker interviews at the end of the study period in the comparison arm. The intervention effect was assessed by difference-in-difference analysis of drug seller treatment practices against national treatment recommendations between the intervention and comparison arms. Observed proportions among care-seeker interviews were compared with corresponding proportions from 5795 child visits recorded in patient registries and 49 direct observations of drug seller-care-seeker encounters in intervention drug shops. RESULTS: The iCCM intervention increased the appropriate treatment of uncomplicated malaria, pneumonia symptoms and non-bloody diarrhoea by 80.2% (95% CI 53.2-107.2), 65.5% (95% CI 51.6-79.4) and 31.4% (95% CI 1.6-61.2), respectively. Within the intervention arm, drug seller scores on appropriate treatment for pneumonia symptoms and diagnostic test use were the same among care-seeker exit interviews and direct observation. A linear trend (negative slope, - 0.009 p value < 0.001) was observed for proportions of child cases prescribed any antimicrobial medicine in the intervention arm drug shops. CONCLUSIONS: The iCCM intervention improved appropriate treatment for uncomplicated malaria, pneumonia symptoms and diarrhoea. Drug seller adherence to iCCM guidelines was high, without causing excessive prescription of antimicrobial medicines in this study. Further research should assess whether this effect is sustained over time and under routine supervision models.

Unpredictability dictates quality of maternal and newborn care provision in rural Tanzania-A qualitative study of health workers' perspectives.

BACKGROUND: Health workers are the key to realising the potential of improved quality of care for mothers and newborns in the weak health systems of Sub Saharan Africa. Their perspectives are fundamental to understand the effectiveness of existing improvement programs and to identify ways to strengthen future initiatives. The objective of this study was therefore to examine health worker perspectives of the conditions for maternal and newborn care provision and their perceptions of what constitutes good quality of care in rural Tanzanian health facilities. METHODS: In February 2014, we conducted 17 in-depth interviews with different cadres of health workers providing maternal and newborn care in 14 rural health facilities in Tandahimba district, south-eastern Tanzania. These facilities included one district hospital, three health centres and ten dispensaries. Interviews were conducted in Swahili, transcribed verbatim and translated into English. A grounded theory approach was used to guide the analysis, the output of which was one core category, four main categories and several sub-categories. RESULTS: 'It is like rain' was identified as the core category, delineating unpredictability as the common denominator for all aspects of maternal and newborn care provision. It implies that conditions such as mothers' access to and utilisation of health care are unreliable; that availability of resources is uncertain and that health workers have to help and try to balance the situation. Quality of care was perceived to vary as a consequence of these conditions. Health workers stressed the importance of predictability, of 'things going as intended', as a sign of good quality care. CONCLUSIONS: Unpredictability emerged as a fundamental condition for maternal and newborn care provision, an important determinant and characteristic of quality in this study. We believe that this finding is also relevant for other areas of care in the same setting and may be an important defining factor of a weak health system. Increasing predictability within health services, and focusing on the experience of health workers within these, should be prioritised in order to achieve better quality of care for mothers and newborns.

Evaluation of Helping Babies Breathe Quality Improvement Cycle (HBB-QIC) on retention of neonatal resuscitation skills six months after training in Nepal.

BACKGROUND: Each year 700,000 infants die due to intrapartum-related complications. Implementation of Helping Babies Breathe (HBB)-a simplified neonatal resuscitation protocol in low-resource clinical settings has shown to reduce intrapartum stillbirths and first-day neonatal mortality. However, there is a lack of evidence on the effect of different HBB implementation strategies to improve and sustain the clinical competency of health workers on bag-and-mask ventilation. This study was conducted to evaluate the impact of multi-faceted implementation strategy for HBB, as a quality improvement cycle (HBB-QIC), on the retention of neonatal resuscitation skills in a tertiary hospital of Nepal. METHODS: A time-series design was applied. The multi-faceted intervention for HBB-QIC included training, daily bag-and-mask skill checks, preparation for resuscitation before every birth, self-evaluation and peer review on neonatal resuscitation skills, and weekly review meetings. Knowledge and skills were assessed through questionnaires, skill checklists, and Objective Structured Clinical Examinations (OSCE) before implementation of the HBB-QIC, immediately after HBB training, and again at 6 months. Means were compared using paired t-tests, and associations between skill retention and HBB-QIC components were analyzed using logistic regression analysis. RESULTS: One hundred thirty seven health workers were enrolled in the study. Knowledge scores were higher immediately following the HBB training, 16.4 ± 1.4 compared to 12.8 ± 1.6 before (out of 17), and the knowledge was retained 6 months after the training (16.5 ± 1.1). Bag-and-mask skills improved immediately after the training and were retained 6 months after the training. The retention of bag-and-mask skills was associated with daily bag-and-mask skill checks, preparation for resuscitation before every birth, use of a self-evaluation checklist, and attendance at weekly review meetings. The implementation strategies with the highest association to skill retention were daily bag-and-mask skill checks (RR-5.1, 95% CI 1.9-13.5) and use of self-evaluation checklists after every delivery (RR-3.8, 95% CI 1.4-9.7). CONCLUSIONS: Health workers who practiced bag-and-mask skills, prepared for resuscitation before every birth, used self-evaluation checklists, and attended weekly review meetings were more likely to retain their neonatal resuscitation skills. Further studies are required to evaluate HBB-QIC in primary care settings, where the number of deliveries is gradually increasing. TRIAL REGISTRATION: ISRCTN97846009 . Date of Registration- 15 August 2012.

Enablers and barriers to evidence based planning in the district health system in Uganda; perceptions of district health managers.

BACKGROUND: The District Health System was endorsed as the key strategy to achieve 'Health for all' during the WHO organized inter-regional meeting in Harare in 1987. Many expectations were put upon the district health system, including planning. Although planning should be evidence based to prioritize activities, in Uganda it has been described as occurring more by chance than by choice. The role of planning is entrusted to the district health managers with support from the Ministry of Health and other stakeholders, but there is limited knowledge on the district health manager's capacity to carry out evidence-based planning. The aim of this study was to determine the barriers and enablers to evidence-based planning at the district level. METHODS: This qualitative study collected data through key informant interviews with district managers from two purposefully selected districts in Uganda that have been implementing evidence-based planning. A deductive process of thematic analysis was used to classify responses within themes. RESULTS: There were considerable differences between the districts in regard to the barriers and enablers for evidence-based planning. Variations could be attributed to specific contextual and environmental differences such as human resource levels, date of establishment of the district, funding and the sociopolitical environment. The perceived lack of local decision space coupled with the perception that the politicians had all the power while having limited knowledge on evidence-based planning was considered an important barrier. CONCLUSION: There is a need to review the mandate of the district managers to make decisions in the planning process and the range of decision space available within the district health system. Given the important role elected officials play in a decentralized system a concerted effort should be made to increase their knowledge on evidence-based planning and the district health system as a whole.