Biometric linkage of longitudinally collected electronic case report forms and confirmation of subject identity: an open framework for ODK and related tools.

The availability of low-cost biometric hardware sensors and software makes it possible to rapidly, affordably and securely sample and store a unique and invariant biological signature (or biometric "template") for the purposes of identification. This has applications in research and trials, particularly for purposes of consent, linkage of case reporting forms collected at different times, and in the confirmation of participant identity for purposes of safety monitoring and adherence to international data laws. More broadly, these methods are applicable to the needs of the billion people who live in resource-restricted settings without identification credentials. The use of mobile electronic data collection software has recently become commonplace in clinical trials, research and actions for public good. A raft of tools based on the open-source ODK project now provide diverse options for data management that work consistently in resource-restricted settings, but none have built-in functionality for capturing biometric templates. In this study, we report the development and validation of a novel open-source app and associated method for capturing and matching biometric fingerprint templates during data collection with the popular data platforms ODK, KoBoToolbox, SurveyCTO, Ona and CommCare. Using data from more than 1,000 fingers, we show that fingerprint templates can be used to link data records with high accuracy. The accuracy of this process increases through the linkage of multiple fingerprints to each data record. By focussing on publishing open-source code and documentation, and by using an affordable (<£50) and mass-produced model of fingerprint sensor, we are able to make this platform freely available to the large global user community that utilises ODK and related data collection systems.

Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK.

Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.

Localising vaccination services: Qualitative insights on public health and minority group collaborations to co-deliver coronavirus vaccines.

Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders' response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.

Antibiotic stories: a mixed-methods, multi-country analysis of household antibiotic use in Malawi, Uganda and Zimbabwe.

BACKGROUND: As concerns about the prevalence of infections that are resistant to available antibiotics increase, attention has turned toward the use of these medicines both within and outside of formal healthcare settings. Much of what is known about use beyond formal settings is informed by survey-based research. Few studies to date have used comparative, mixed-methods approaches to render visible patterns of use within and between settings as well as wider points of context shaping these patterns. DESIGN: This article analyses findings from mixed-methods anthropological studies of antibiotic use in a range of rural and urban settings in Zimbabwe, Malawi and Uganda between 2018 and 2020. All used a 'drug bag' survey tool to capture the frequency and types of antibiotics used among 1811 households. We then undertook observations and interviews in residential settings, with health providers and key stakeholders to better understand the stories behind the most-used antibiotics. RESULTS: The most self-reported 'frequently used' antibiotics across settings were amoxicillin, cotrimoxazole and metronidazole. The stories behind their use varied between settings, reflecting differences in the configuration of health systems and antibiotic supplies. At the same time, these stories reveal cross-cutting features and omissions of contemporary global health programming that shape the contours of antibiotic (over)use at national and local levels. CONCLUSIONS: Our findings challenge the predominant focus of stewardship frameworks on the practices of antibiotic end users. We suggest future interventions could consider systems-rather than individuals-as stewards of antibiotics, reducing the need to rely on these medicines to fix other issues of inequity, productivity and security.

Electronic Data Management for Vaccine Trials in Low Resource Settings: Upgrades, Scalability, and Impact of ODK.

Background: ODK provides software and standards that are popular solutions for off-grid electronic data collection and has substantial code overlap and interoperability with a number of related software products including CommCare, Enketo, Ona, SurveyCTO, and KoBoToolbox. These tools provide open-source options for off-grid use in public health data collection, management, analysis, and reporting. During the 2018-2020 Ebola epidemic in the North Kivu and Ituri regions of Democratic Republic of Congo, we used these tools to support the DRC Ministère de la Santé RDC and World Health Organization in their efforts to administer an experimental vaccine (VSV-Zebov-GP) as part of their strategy to control the transmission of infection. Method: New functions were developed to facilitate the use of ODK, Enketo and R in large scale data collection, aggregation, monitoring, and near-real-time analysis during clinical research in health emergencies. We present enhancements to ODK that include a built-in audit-trail, a framework and companion app for biometric registration of ISO/IEC 19794-2 fingerprint templates, enhanced performance features, better scalability for studies featuring millions of data form submissions, increased options for parallelization of research projects, and pipelines for automated management and analysis of data. We also developed novel encryption protocols for enhanced web-form security in Enketo. Results: Against the backdrop of a complex and challenging epidemic response, our enhanced platform of open tools was used to collect and manage data from more than 280,000 eligible study participants who received VSV-Zebov-GP under informed consent. These data were used to determine whether the VSV-Zebov-GP was safe and effective and to guide daily field operations. Conclusions: We present open-source developments that make electronic data management during clinical research and health emergencies more viable and robust. These developments will also enhance and expand the functionality of a diverse range of data collection platforms that are based on the ODK software and standards.

Considerations for mitigating COVID-19 related risks in schools.

As the new school year begins in the United States, school districts will be tasked with providing in-person teaching while keeping children and school staff safe, an increasingly difficult goal in the presence of the COVID-19 delta variant. We aim to provide updated interpretations of past and newly published studies to assist in assessing risk in schools, and to add additional perspectives on addressing the social determinants of learning and on the role of race and other social factors. We advocate for the continued implementation of risk mitigation strategies in schools, including mandatory mask policies, improved ventilation, and convenient access to vaccinations for those eligible, as recommended by the CDC, and to use this opportunity to make long-term improvements to our schools as a matter of urgency.

SARS-CoV-2 seroprevalence in a strictly-Orthodox Jewish community in the UK: A retrospective cohort study.

BACKGROUND: Ethnic and religious minorities have been disproportionately affected by SARS-CoV-2 worldwide. The UK strictly-Orthodox Jewish community has been severely affected by the pandemic. This group shares characteristics with other ethnic minorities including larger family sizes, higher rates of household crowding and relative socioeconomic deprivation. We studied a UK strictly-Orthodox Jewish population to understand transmission of COVID-19 within this community. METHODS: We performed a household-focused cross-sectional SARS-CoV-2 serosurvey between late-October and early December 2020 prior to the third national lockdown. Randomly-selected households completed a standardised questionnaire and underwent serological testing with a multiplex assay for SARS-CoV-2 IgG antibodies. We report clinical illness and testing before the serosurvey, seroprevalence stratified by age and sex. We used random-effects models to identify factors associated with infection and antibody titres. FINDINGS: A total of 343 households, consisting of 1,759 individuals, were recruited. Serum was available for 1,242 participants. The overall seroprevalence for SARS-CoV-2 was 64.3% (95% CI 61.6-67.0%). The lowest seroprevalence was 27.6% in children under 5 years and rose to 73.8% in secondary school children and 74% in adults. Antibody titres were higher in symptomatic individuals and declined over time since reported COVID-19 symptoms, with the decline more marked for nucleocapsid titres. INTERPRETATION: In this tight-knit religious minority population in the UK, we report one of the highest SARS-CoV-2 seroprevalence levels in the world to date, which was markedly higher than the reported 10% seroprevalence in London at the time of the study. In the context of this high force of infection, all age groups experienced a high burden of infection. Actions to reduce the burden of disease in this and other minority populations are urgently required. FUNDING: This work was jointly funded by UKRI and NIHR [COV0335; MR/V027956/1], a donation from the LSHTM Alumni COVID-19 response fund, HDR UK, the MRC and the Wellcome Trust.

Unequal impact of the COVID-19 crisis on minority ethnic groups: a framework for understanding and addressing inequalities.

Minority ethnic groups have been disproportionately affected by the COVID-19 pandemic. While the exact reasons for this remain unclear, they are likely due to a complex interplay of factors rather than a single cause. Reducing these inequalities requires a greater understanding of the causes. Research to date, however, has been hampered by a lack of theoretical understanding of the meaning of 'ethnicity' (or race) and the potential pathways leading to inequalities. In particular, quantitative analyses have often adjusted away the pathways through which inequalities actually arise (ie, mediators for the effect of interest), leading to the effects of social processes, and particularly structural racism, becoming hidden. In this paper, we describe a framework for understanding the pathways that have generated ethnic (and racial) inequalities in COVID-19. We suggest that differences in health outcomes due to the pandemic could arise through six pathways: (1) differential exposure to the virus; (2) differential vulnerability to infection/disease; (3) differential health consequences of the disease; (4) differential social consequences of the disease; (5) differential effectiveness of pandemic control measures and (6) differential adverse consequences of control measures. Current research provides only a partial understanding of some of these pathways. Future research and action will require a clearer understanding of the multiple dimensions of ethnicity and an appreciation of the complex interplay of social and biological pathways through which ethnic inequalities arise. Our framework highlights the gaps in the current evidence and pathways that need further investigation in research that aims to address these inequalities.

Trust and transparency in times of crisis: Results from an online survey during the first wave (April 2020) of the COVID-19 epidemic in the UK.

BACKGROUND: The success of a government's COVID-19 control strategy relies on public trust and broad acceptance of response measures. We investigated public perceptions of the UK government's COVID-19 response, focusing on the relationship between trust and perceived transparency, during the first wave (April 2020) of the COVID-19 pandemic in the United Kingdom. METHODS: Anonymous survey data were collected (2020-04-06 to 2020-04-22) from 9,322 respondents, aged 20+ using an online questionnaire shared primarily through Facebook. We took an embedded-mixed-methods approach to data analysis. Missing data were imputed via multiple imputation. Binomial & multinomial logistic regression were used to detect associations between demographic characteristics and perceptions or opinions of the UK government's response to COVID-19. Structural topic modelling (STM), qualitative thematic coding of sub-sets of responses were then used to perform a thematic analysis of topics that were of interest to key demographic groups. RESULTS: Most respondents (95.1%) supported government enforcement of behaviour change. While 52.1% of respondents thought the government was making good decisions, differences were apparent across demographic groups, for example respondents from Scotland had lower odds of responding positively than respondents in London. Higher educational levels saw decreasing odds of having a positive opinion of the government response and decreasing household income associated with decreasing positive opinion. Of respondents who thought the government was not making good decisions 60% believed the economy was being prioritised over people and their health. Positive views on government decision-making were associated with positive views on government transparency about the COVID-19 response. Qualitative analysis about perceptions of government transparency highlighted five key themes: (1) the justification of opacity due to the condition of crisis, (2) generalised mistrust of politics, (3) concerns about the role of scientific evidence, (4) quality of government communication and (5) questions about political decision-making processes. CONCLUSION: Our study suggests that trust is not homogenous across communities, and that generalised mistrust, concerns about the transparent use and communication of evidence and insights into decision-making processes can affect perceptions of the government's pandemic response. We recommend targeted community engagement, tailored to the experiences of different groups and a new focus on accountability and openness around how decisions are made in the response to the UK COVID-19 pandemic.

Effects of galacto-oligosaccharide prebiotics in blood profile of severely acute malnourished children.

This study assessed the effects of galacto-oligosaccharides (Oligomate) on hematocrit, serum enzymes, total bilirubin levels, and serum electrolytes in controls and severely malnourished infants, with emphasis on gastrointestinal symptoms. Oligomate doses and phases did not affect stools frequency per day, indicating that prebiotic effect on stool may be due to the prebiotic type. The number of vomits per day during phases 2 and 3 were significantly reduced (p<0.05) in response to prebiotics, despite the prebiotic dose effect was not significant (p>0.05). Moreover, prebiotics administration during phases 2 and 3 markedly improved hemoglobin levels (p<0.05), but not the dose. Similarly, hematocrit levels and white blood cells were significantly improved during the last 2 phases, but dose have no effects on blood hematocrit levels. Erythrocyte sedimentation rate significantly decreased (p<0.05) in phases 2 and 3 compared to phase 1. No dose-related effect was stated on erythrocytes sedimentation rate. Regarding the serum enzymes, SGPT significantly decreased (p<0.05) in phases 2 and 3 compared to phase 1, whereas SGOT significantly decreased only in phase 3. Total bilirubin levels increased significantly (p<0.05) in phase 3 when compared to phases 1 or 2. Prebiotics significantly decreased (p<0.05) sodium levels in the treated group, while potassium levels did not change in all groups, excepting during phase 2, where it increased significantly. Thus, our results confirm the hypothesis that prebiotic supplementation improves blood parameters and health status, consequently decreasing the infection risk and number of vomit per day in infants.

Treatment of Sick Children Seeking Care in the Private Health Sector in Uganda: A Cluster Randomized Trial.

The main objective of this study was to assess whether training of private health providers and community sensitization on the importance of effective prompt care seeking and the need for referral could improve treatment of sick children in the private health sector in Uganda. Private providers were trained to diagnose and treat sick children according to the integrated community case management (iCCM) guidelines. In the control arm, routine services were offered. The outcomes were seeking care within 24 hours of onset of symptoms and appropriate case management for malaria, pneumonia, and diarrhea among children aged < 5 years. A total of 10,809 sick children (5,955 in the intervention arm and 4,854 in the control arm) presented for diagnosis and treatment. The percentage seeking care within 24 hours of onset of symptoms was 45.4% (95% CI 36.0-48.8) in the intervention arm versus 43.9% (95% CI 38.1-49.8) in the control arm (P = 0.04). Adherence to malaria rapid diagnostic test (mRDT) results was high, with 1,459 (94.3%) in the intervention arm versus 1,402 (83.0%) in the control arm (P = 0.04). Appropriate treatment of mRDT-positive children with artemisinin-based combination therapy was seen in 93.1% (95% CI 88.5-97.7) in the intervention arm versus 85.1% (95% CI 78.6-91.7) in the control arm (P = 0.03). Adherence to iCCM guidelines was very high: 89.1% of children with diarrhea in the intervention arm and 80.4% in the control arm were given oral rehydration salts and zinc (P = 0.01). Of the children with a respiratory rate > 40 breaths/minute, 1,596 (85.1%) in the intervention arm versus 104 (54.5%) in the control arm were given amoxicillin (P = 0.01). In conclusion, the intervention improved treatment of malaria, pneumonia, and diarrhea because of provider adherence to treatment guidelines. The policy implications of these findings are to initiate a dialogue at district and national levels on how to scale up the intervention in the private sector. NCT02450630 registered with ClinicalTrials.gov: May 9, 2015.

Caregivers' compliance with referral advice: evidence from two studies introducing mRDTs into community case management of malaria in Uganda.

BACKGROUND: Several malaria endemic countries have implemented community health worker (CHW) programmes to increase access to populations underserved by health care. There is considerable evidence on CHW adherence to case management guidelines, however, there is limited evidence on the compliance to referral advice and the outcomes of children under-5 referred by CHWs. This analysis examined whether caregivers complied with CHWs referral advice. METHODS: Data from two cluster (village) randomised trials, one in a moderate-to-high malaria transmission setting, another in a low-transmission setting conducted between January 2010-July 2011 were analysed. CHW were trained to recognise signs and symptoms that required referral to a health centre. CHW in the intervention arm also had training on; malaria rapid diagnostic tests (mRDT) and administering artemisinin based combination therapy (ACT); CHW in the control arm were trained to treat malaria with ACTs based on fever symptoms. Caregivers' referral forms were linked with CHW treatment forms to determine whether caregivers complied with the referral advice. Factors associated with compliance were examined with logistic regression. RESULTS: CHW saw 18,497 child visits in the moderate-to-high transmission setting and referred 15.2% (2815/18,497) of all visits; in the low-transmission setting, 35.0% (1135/3223) of all visits were referred. Compliance to referral was low, in both settings < 10% of caregivers complied with referral advice. In the moderate-to-high transmission setting compliance was higher if children were tested with mRDT compared to children who were not tested with mRDT. In both settings, nearly all children treated with pre-referral rectal artesunate failed to comply with referral and compliance was independently associated with factors such as health centre distance and day of referral by a CHW. In the moderate-to-high transmission setting, time of presentation, severity of referral were also associated with compliance, whilst in the low-transmission setting, compliance was low if an ACT was prescribed. CONCLUSIONS: This analysis suggests there are several barriers to comply with CHWs referral advice by caregivers. This is concerning for children who received rectal artesunate. As CHW programmes continue scale-up, barriers to referral compliance need to be addressed to ensure a continuum of care from the community to the health centre. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov. Identifier NCT01048801 , 13th January 2010.

Cost-effectiveness analysis of introducing malaria diagnostic testing in drug shops: A cluster-randomised trial in Uganda.

BACKGROUND: Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. METHODS: Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs following presumptive diagnosis of malaria in the control arm. The effect on the proportion of customers with fever 'appropriately treated of malaria with ACT' was captured during a randomised trial in drug shops in Mukono District, Uganda. Health sector costs included: training of drug shop vendors, community sensitisation, supervision and provision of mRDTs and ACTs to drug shops. Household costs of treatment-seeking were captured in a representative sample of drug shop customers. FINDINGS: The introduction of mRDTs in drug shops was associated with a large improvement of diagnosis and treatment of malaria, resulting in low incremental costs for the health sector at US$0.55 per patient appropriately treated of malaria. High expenditure on non-ACT drugs by households contributed to higher incremental societal costs of US$3.83. Sensitivity analysis showed that mRDTs would become less cost-effective compared to presumptive diagnosis with increasing malaria prevalence and lower adherence to negative mRDT results. CONCLUSION: mRDTs in drug shops improved the targeting of ACTs to malaria patients and are likely to be considered cost-effective compared to presumptive diagnosis, although the increased costs borne by households when the test result is negative are a concern.

The Impact of Introducing Malaria Rapid Diagnostic Tests on Fever Case Management: A Synthesis of Ten Studies from the ACT Consortium.

Since 2010, the World Health Organization has been recommending that all suspected cases of malaria be confirmed with parasite-based diagnosis before treatment. These guidelines represent a paradigm shift away from presumptive antimalarial treatment of fever. Malaria rapid diagnostic tests (mRDTs) are central to implementing this policy, intended to target artemisinin-based combination therapies (ACT) to patients with confirmed malaria and to improve management of patients with nonmalarial fevers. The ACT Consortium conducted ten linked studies, eight in sub-Saharan Africa and two in Afghanistan, to evaluate the impact of mRDT introduction on case management across settings that vary in malaria endemicity and healthcare provider type. This synthesis includes 562,368 outpatient encounters (study size range 2,400-432,513). mRDTs were associated with significantly lower ACT prescription (range 8-69% versus 20-100%). Prescribing did not always adhere to malaria test results; in several settings, ACTs were prescribed to more than 30% of test-negative patients or to fewer than 80% of test-positive patients. Either an antimalarial or an antibiotic was prescribed for more than 75% of patients across most settings; lower antimalarial prescription for malaria test-negative patients was partly offset by higher antibiotic prescription. Symptomatic management with antipyretics alone was prescribed for fewer than 25% of patients across all scenarios. In community health worker and private retailer settings, mRDTs increased referral of patients to other providers. This synthesis provides an overview of shifts in case management that may be expected with mRDT introduction and highlights areas of focus to improve design and implementation of future case management programs.

Introducing rapid tests for malaria into the retail sector: what are the unintended consequences?

The observation that many people in Africa seek care for febrile illness in the retail sector has led to a number of public health initiatives to try to improve the quality of care provided in these settings. The potential to support the introduction of rapid diagnostic tests for malaria (mRDTs) into drug shops is coming under increased scrutiny. Those in favour argue that it enables the harmonisation of policy around testing and treatment for malaria and maintains a focus on market-based solutions to healthcare. Despite the enthusiasm among many global health actors for this policy option, there is a limited understanding of the consequences of the introduction of mRDTs in the retail sector. We undertook an interpretive, mixed methods study with drug shop vendors (DSVs), their clients and local health workers to explore the uses and interpretations of mRDTs as they became part of daily practice in drug shops during a trial in Mukono District, Uganda. This paper reports the unintended consequences of their introduction. It describes how the test engendered trust in the professional competence of DSVs; was misconstrued by clients and providers as enabling a more definitive diagnosis of disease in general rather than malaria alone; that blood testing made drug shops more attractive places to seek care than they had previously been; was described as shifting treatment-seeking behaviour away from formal health centres and into drug shops; and influenced an increase in sales of medications, particularly antibiotics. TRIAL REGISTRATION NUMBER: NCT01194557; Results.

Comparison of the capacity between public and private health facilities to manage under-five children with febrile illnesses in Uganda.

BACKGROUND: Public health facilities are usually the first to receive interventions compared to private facilities, yet majority of health seeking care is first done with the latter. This study compared the capacity to manage acute febrile illnesses in children below 5 years in private vs public health facilities in order to design interventions to improve quality of care. METHODS: A survey was conducted within 57 geographical areas (parishes), from August to October 2014 in Mukono district, central Uganda. The survey comprised both facility and health worker assessment. Data were collected on drug stocks, availability of treatment guidelines, diagnostic equipment, and knowledge in management of malaria, pneumonia and diarrhoea, using a structured questionnaire. RESULTS: A total of 53 public and 241 private health facilities participated in the study. While similar proportions of private and public health facilities stocked Coartem, the first-line anti-malarial drug, (98 vs 95%, p = 0.22), significantly more private than public health facilities stocked quinine (85 vs 53%, p < 0.01). Stocks of obsolete anti-malarial drugs, such as chloroquine, were reported in few public and private facilities (3.7 vs 12.5%, p = 0.06). Stocks of antibiotics-amoxycillin and gentamycin were similar in both sectors (≥90% for amoxicillin; ≥50 for gentamycin). Training in malaria was reported by 65% of public health facilities vs 56% in the private sector, p = 0.25), while, only 21% in the public facility and 12% in the private facilities, p = 0.11, reported receiving training in pneumonia. Only 55% of public facilities had microscopes. Malaria treatment guidelines were significantly lacking in the private sector, p = 0.01. Knowledge about first-line management of uncomplicated malaria, pneumonia and diarrhoea was significantly better in the public facilities compared to the private ones, though still sub-optimal. CONCLUSION: Deficiencies of equipment, supplies and training exist even in public health facilities. In order to significantly improve the capacity to handle acute febrile illness among children under five, training in proper case management, availability of supplies and diagnostics need to be addressed in both sectors.

Cost-effectiveness analysis of malaria rapid diagnostic tests for appropriate treatment of malaria at the community level in Uganda.

In Sub-Saharan Africa, malaria remains a major cause of morbidity and mortality among children under 5, due to lack of access to prompt and appropriate diagnosis and treatment. Many countries have scaled-up community health workers (CHWs) as a strategy towards improving access. The present study was a cost-effectiveness analysis of the introduction of malaria rapid diagnostic tests (mRDTs) performed by CHWs in two areas of moderate-to-high and low malaria transmission in rural Uganda. CHWs were trained to perform mRDTs and treat children with artemisinin-based combination therapy (ACT) in the intervention arm while CHWs offered treatment based on presumptive diagnosis in the control arm. Data on the proportion of children with fever 'appropriately treated for malaria with ACT' were captured from a randomised trial. Health sector costs included: training of CHWs, community sensitisation, supervision, allowances for CHWs and provision of mRDTs and ACTs. The opportunity costs of time utilised by CHWs were estimated based on self-reporting. Household costs of subsequent treatment-seeking at public health centres and private health providers were captured in a sample of households. mRDTs performed by CHWs was associated with large improvements in appropriate treatment of malaria in both transmission settings. This resulted in low incremental costs for the health sector at US$3.0 per appropriately treated child in the moderate-to-high transmission area. Higher incremental costs at US$13.3 were found in the low transmission area due to lower utilisation of CHW services and higher programme costs. Incremental costs from a societal perspective were marginally higher. The use of mRDTs by CHWs improved the targeting of ACTs to children with malaria and was likely to be considered a cost-effective intervention compared to a presumptive diagnosis in the moderate-to-high transmission area. In contrast to this, in the low transmission area with low attendance, RDT use by CHWs was not a low cost intervention.

Improving prescribing practices with rapid diagnostic tests (RDTs): synthesis of 10 studies to explore reasons for variation in malaria RDT uptake and adherence.

OBJECTIVES: The overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts. DESIGN: A comparative case study approach, analysing variation in outcomes across different settings. SETTING: Studies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case. PARTICIPANTS: 28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria. INTERVENTIONS: The interventions included different mRDT training packages, supervision, supplies and community sensitisation. OUTCOME MEASURES: Analysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial). RESULTS: Outcomes varied widely across cases: 12-100% mRDT uptake; 44-98% adherence to positive mRDTs; 27-100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs. CONCLUSIONS: Basic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce.

Introducing malaria rapid diagnostic tests in private medicine retail outlets: A systematic literature review.

BACKGROUND: Many patients with malaria-like symptoms seek treatment in private medicine retail outlets (PMR) that distribute malaria medicines but do not traditionally provide diagnostic services, potentially leading to overtreatment with antimalarial drugs. To achieve universal access to prompt parasite-based diagnosis, many malaria-endemic countries are considering scaling up malaria rapid diagnostic tests (RDTs) in these outlets, an intervention that may require legislative changes and major investments in supporting programs and infrastructures. This review identifies studies that introduced malaria RDTs in PMRs and examines study outcomes and success factors to inform scale up decisions. METHODS: Published and unpublished studies that introduced malaria RDTs in PMRs were systematically identified and reviewed. Literature published before November 2016 was searched in six electronic databases, and unpublished studies were identified through personal contacts and stakeholder meetings. Outcomes were extracted from publications or provided by principal investigators. RESULTS: Six published and six unpublished studies were found. Most studies took place in sub-Saharan Africa and were small-scale pilots of RDT introduction in drug shops or pharmacies. None of the studies assessed large-scale implementation in PMRs. RDT uptake varied widely from 8%-100%. Provision of artemisinin-based combination therapy (ACT) for patients testing positive ranged from 30%-99%, and was more than 85% in five studies. Of those testing negative, provision of antimalarials varied from 2%-83% and was less than 20% in eight studies. Longer provider training, lower RDT retail prices and frequent supervision appeared to have a positive effect on RDT uptake and provider adherence to test results. Performance of RDTs by PMR vendors was generally good, but disposal of medical waste and referral of patients to public facilities were common challenges. CONCLUSIONS: Expanding services of PMRs to include malaria diagnostic services may hold great promise to improve malaria case management and curb overtreatment with antimalarials. However, doing so will require careful planning, investment and additional research to develop and sustain effective training, supervision, waste-management, referral and surveillance programs beyond the public sector.

Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings.

Objectives To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia.Design Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).Setting Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.Participants 522 480 children and adults with acute febrile illness.Interventions Rapid diagnostic tests for malaria.Main outcome measures Proportions of patients for whom an antibiotic was prescribed in trial groups who had undergone rapid diagnostic testing compared with controls and in patients with negative test results compared with patients with positive results. A secondary aim compared classes of antibiotics prescribed in different settings.Results Antibiotics were prescribed to 127 052/238 797 (53%) patients in control groups and 167 714/283 683 (59%) patients in intervention groups. Antibiotics were prescribed to 40% (35 505/89 719) of patients with a positive test result for malaria and to 69% (39 400/57 080) of those with a negative result. All but one study showed a trend toward more antibiotic prescribing in groups who underwent rapid diagnostic tests. Random effects meta-analysis of the trials showed that the overall risk of antibiotic prescription was 21% higher (95% confidence interval 7% to 36%) in intervention settings. In most intervention settings, patients with negative test results received more antibiotic prescriptions than patients with positive results for all the most commonly used classes: penicillins, trimethoprim-sulfamethoxazole (one exception), tetracyclines, and metronidazole.Conclusions Introduction of rapid diagnostic tests for malaria to reduce unnecessary use of antimalarials-a beneficial public health outcome-could drive up untargeted use of antibiotics. That 69% of patients were prescribed antibiotics when test results were negative probably represents overprescription.This included antibiotics from several classes, including those like metronidazole that are seldom appropriate for febrile illness, across varied clinical, health system, and epidemiological settings. It is often assumed that better disease specific diagnostics will reduce antimicrobial overuse, but they might simply shift it from one antimicrobial class to another. Current global implementation of malaria testing might increase untargeted antibiotic use and must be examined.