The role of 'hidden' community volunteers in community-based health service delivery platforms: examples from sub-Saharan Africa

Community-based research on child survival in sub-Saharan Africa has focussed on the increased provision of curative health services by a formalised cadre of lay community health workers (CHWs), but we have identified a particular configuration, that deserves closer scrutiny. We identified a two-tiered CHW system, with the first tier being the lessor known or 'hidden' community/village level volunteers and the second tier being formal, paid CHWs, in Ethiopia, Mali, and Niger. Whilst the disease-focussed tasks of the formal CHW tier may be more amenable to classic epidemiological surveillance, we postulate that understanding the relationship between formalised CHWs and volunteer cadres, in terms of scope, location of practice and ratio to population, would be important for a comprehensive evaluation of child survival in these countries.We report on the findings from our joint qualitative and quantitative investigations, highlighting the need to recognise the 'hidden' contribution of volunteers. We need to better characterize the volunteers' interaction with community-based and primary care services and to better understand ways to improve the volunteer systems with the right type of investments. This is particularly important for considering the models for scale-up of CHWs in sub-Saharan Africa.IS

Niger's child survival success, contributing factors and challenges to sustainability: a retrospective analysis

BACKGROUND: Household surveys undertaken in Niger since 1998 have revealed steady declines in under-5 mortality which have placed the country 'on track' to reach the fourth Millennium Development goal (MDG). This paper explores Niger's mortality and health coverage data for children under-5 years of age up to 2012 to describe trends in high impact interventions and the resulting impact on childhood deaths averted. The sustainability of these trends are also considered. Methods and FINDINGS: Estimates of child mortality using the 2012 Demographic and Health Survey were developed and maternal and child health coverage indicators were calculated over four time periods. Child survival policies and programmes were documented through a review of documents and key informant interviews. The Lives Saved Tool (LiST) was used to estimate the number of child lives saved and identify which interventions had the largest impact on deaths averted. The national mortality rate in children under-5 decreased from 286 child deaths per 1000 live births (95% confidence interval 177 to 394) in the period 1989-1990 to 128 child deaths per 1000 live births in the period 2011-2012 (101 to 155), corresponding to an annual rate of decline of 3.6%, with significant declines taking place after 1998. Improvements in the coverage of maternal and child health interventions between 2006 and 2012 include one and four or more antenatal visits, maternal Fansidar and tetanus toxoid vaccination, measles and DPT3 vaccinations, early and exclusive breastfeeding, oral rehydration salts (ORS) and proportion of children sleeping under an insecticide-treated bed net (ITN). Approximately 26,000 deaths of children under-5 were averted in 2012 due to decreases in stunting rates (27%), increases in ORS (14%), the Hib vaccine (14%), and breastfeeding (11%). Increases in wasting and decreases in vitamin A supplementation negated some of those gains. Care seeking at the community level was responsible for an estimated 7,800 additional deaths averted in 2012. A major policy change occurred in 2006 enabling free health care provision for women and children, and in 2008 the establishment of a community health worker programme. CONCLUSION: Increases in access and coverage of care for mothers and children have averted a considerable number of childhood deaths. The 2006 free health care policy and health post expansion were paramount in reducing barriers to care. However the sustainability of this policy and health service provision is precarious in light of persistently high fertility rates, unpredictable GDP growth, a high dependence on donor support and increasing pressures on government funding

In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection

Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization

Model SNP development for complex genomes based on hexaploid oat using high-throughput 454 sequencing technology

<p>Abstract</p> <p>Background</p> <p>Genetic markers are pivotal to modern genomics research; however, discovery and genotyping of molecular markers in oat has been hindered by the size and complexity of the genome, and by a scarcity of sequence data. The purpose of this study was to generate oat expressed sequence tag (EST) information, develop a bioinformatics pipeline for SNP discovery, and establish a method for rapid, cost-effective, and straightforward genotyping of SNP markers in complex polyploid genomes such as oat.</p> <p>Results</p> <p>Based on cDNA libraries of four cultivated oat genotypes, approximately 127,000 contigs were assembled from approximately one million Roche 454 sequence reads. Contigs were filtered through a novel bioinformatics pipeline to eliminate ambiguous polymorphism caused by subgenome homology, and 96 <it>in silico </it>SNPs were selected from 9,448 candidate loci for validation using high-resolution melting (HRM) analysis. Of these, 52 (54%) were polymorphic between parents of the Ogle1040 × TAM O-301 (OT) mapping population, with 48 segregating as single Mendelian loci, and 44 being placed on the existing OT linkage map. Ogle and TAM amplicons from 12 primers were sequenced for SNP validation, revealing complex polymorphism in seven amplicons but general sequence conservation within SNP loci. Whole-amplicon interrogation with HRM revealed insertions, deletions, and heterozygotes in secondary oat germplasm pools, generating multiple alleles at some primer targets. To validate marker utility, 36 SNP assays were used to evaluate the genetic diversity of 34 diverse oat genotypes. Dendrogram clusters corresponded generally to known genome composition and genetic ancestry.</p> <p>Conclusions</p> <p>The high-throughput SNP discovery pipeline presented here is a rapid and effective method for identification of polymorphic SNP alleles in the oat genome. The current-generation HRM system is a simple and highly-informative platform for SNP genotyping. These techniques provide a model for SNP discovery and genotyping in other species with complex and poorly-characterized genomes.</p

Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study

Background: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related deaths, with a 10-week mortality rate of 25–30%. Fungal load assessed by colony-forming unit (CFU) counts is used as a prognostic marker and to monitor response to treatment in research studies. PCR-based assessment of fungal load could be quicker and less labour-intensive. We sought to design, optimise, and validate quantitative PCR (qPCR) assays for the detection, identification, and quantification of Cryptococcus infections in patients with cryptococcal meningitis in sub-Saharan Africa. Methods: We developed and validated species-specific qPCR assays based on DNA amplification of QSP1 (QSP1A specific to Cryptococcus neoformans, QSP1B/C specific to Cryptococcus deneoformans, and QSP1D specific to Cryptococcus gattii species) and a pan-Cryptococcus assay based on a multicopy 28S rRNA gene. This was a longitudinal study that validated the designed assays on cerebrospinal fluid (CSF) of 209 patients with cryptococcal meningitis at baseline (day 0) and during anti-fungal therapy (day 7 and day 14), from the AMBITION-cm trial in Botswana and Malawi (2018–21). Eligible patients were aged 18 years or older and presenting with a first case of cryptococcal meningitis. Findings: When compared with quantitative cryptococcal culture as the reference, the sensitivity of the 28S rRNA was 98·2% (95% CI 95·1–99·5) and of the QSP1 assay was 90·4% (85·2–94·0) in CSF at day 0. Quantification of the fungal load with QSP1 and 28S rRNA qPCR correlated with quantitative cryptococcal culture (R2=0·73 and R2=0·78, respectively). Both Botswana and Malawi had a predominant C neoformans prevalence of 67% (95% CI 55–75) and 68% (57–73), respectively, and lower C gattii rates of 21% (14–31) and 8% (4–14), respectively. We identified ten patients that, after 14 days of treatment, harboured viable but non-culturable yeasts based on QSP1 RNA detection (without any positive CFU in CSF culture). Interpretation: QSP1 and 28S rRNA assays are useful in identifying Cryptococcus species. qPCR results correlate well with baseline quantitative cryptococcal culture and show a similar decline in fungal load during induction therapy. These assays could be a faster alternative to quantitative cryptococcal culture to determine fungal load clearance. The clinical implications of the possible detection of viable but non-culturable cells in CSF during induction therapy remain unclear. Funding: European and Developing Countries Clinical Trials Partnership; Swedish International Development Cooperation Agency; Wellcome Trust/UK Medical Research Council/UKAID Joint Global Health Trials; and UK National Institute for Health Research

Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study

Background: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related deaths, with a 10-week mortality rate of 25–30%. Fungal load assessed by colony-forming unit (CFU) counts is used as a prognostic marker and to monitor response to treatment in research studies. PCR-based assessment of fungal load could be quicker and less labour-intensive. We sought to design, optimise, and validate quantitative PCR (qPCR) assays for the detection, identification, and quantification of Cryptococcus infections in patients with cryptococcal meningitis in sub-Saharan Africa. Methods: We developed and validated species-specific qPCR assays based on DNA amplification of QSP1 (QSP1A specific to Cryptococcus neoformans, QSP1B/C specific to Cryptococcus deneoformans, and QSP1D specific to Cryptococcus gattii species) and a pan-Cryptococcus assay based on a multicopy 28S rRNA gene. This was a longitudinal study that validated the designed assays on cerebrospinal fluid (CSF) of 209 patients with cryptococcal meningitis at baseline (day 0) and during anti-fungal therapy (day 7 and day 14), from the AMBITION-cm trial in Botswana and Malawi (2018–21). Eligible patients were aged 18 years or older and presenting with a first case of cryptococcal meningitis. Findings: When compared with quantitative cryptococcal culture as the reference, the sensitivity of the 28S rRNA was 98·2% (95% CI 95·1–99·5) and of the QSP1 assay was 90·4% (85·2–94·0) in CSF at day 0. Quantification of the fungal load with QSP1 and 28S rRNA qPCR correlated with quantitative cryptococcal culture (R2=0·73 and R2=0·78, respectively). Both Botswana and Malawi had a predominant C neoformans prevalence of 67% (95% CI 55–75) and 68% (57–73), respectively, and lower C gattii rates of 21% (14–31) and 8% (4–14), respectively. We identified ten patients that, after 14 days of treatment, harboured viable but non-culturable yeasts based on QSP1 RNA detection (without any positive CFU in CSF culture). Interpretation: QSP1 and 28S rRNA assays are useful in identifying Cryptococcus species. qPCR results correlate well with baseline quantitative cryptococcal culture and show a similar decline in fungal load during induction therapy. These assays could be a faster alternative to quantitative cryptococcal culture to determine fungal load clearance. The clinical implications of the possible detection of viable but non-culturable cells in CSF during induction therapy remain unclear

A proposed model to conduct process and outcome evaluations and implementation research of child health programs in Africa using integrated community case management as an example

To use a newly devised set of criteria to review the study design and scope of collection of process, outcomes and contextual data for evaluations and implementation research of integrated community case management (iCCM) in Sub–Saharan Africa. We examined 24 program evaluations and implementation research studies of iCCM in sub–Saharan Africa conducted in the last 5 years (2008–2013), assessed the design used and categorized them according to whether or not they collected sufficient information to conduct process and outcome evaluations. Several evaluations were done too soon after implementation, lacked information on health facility treatments, costs, demand, timeliness or SES and/or did not have a counterfactual. We propose several study designs and minimal data elements to be collected to provide sufficient information to assess whether iCCM increased timely coverage of treatment for the neediest children in a cost–efficient manner

Does adjusting for recall in trend analysis affect coverage estimates for maternal and child health indicators? An analysis of DHS and MICS survey data

Background: The Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) are the major data sources in low- and middle-income countries (LMICs) for evaluating health service coverage. For certain maternal and child health (MCH) indicators, the two surveys use different recall periods: 5 years for DHS and 2 years for MICS. Objective: We explored whether the different recall periods for DHS and MICS affect coverage trend analyses as well as missing data and coverage estimates. Designs: We estimated coverage, using proportions with 95% confidence intervals, for four MCH indicators: intermittent preventive treatment of malaria in pregnancy, tetanus vaccination, early breastfeeding and postnatal care. Trends in coverage were compared using data from 1) standard 5-year DHS and 2-year MICS recall periods (unmatched) and 2) DHS restricted to 2-year recall to match the MICS 2-year recall periods (matched). Linear regression was used to explore the relationship between length of recall, missing data and coverage estimates. Results: Differences in coverage trends were observed between matched and unmatched data in 7 of 18 (39%) comparisons performed. The differences were in the direction of the trend over time, the slope of the coverage change or the significance levels. Consistent trends were seen in 11 of the 18 (61%) comparisons. Proportion of missing data was inversely associated with coverage estimates in both short (2 years) and longer (5 years) recall of the DHS (r=−0.3, p=0.02 and r=−0.4, p=0.004, respectively). The amount of missing information was increased for longer recall compared with shorter recall for all indicators (significant odds ratios ranging between 1.44 and 7.43). Conclusions: In a context where most LMICs are dependent on population-based household surveys to derive coverage estimates, users of these types of data need to ensure that variability in recall periods and the proportion of missing data across data sources are appropriately accounted for when trend analyses are conducted

Where to from here? Policy and financing of integrated community case management (iCCM) of childhood illness in sub–Saharan Africa

In sub–Saharan Africa, recent years have seen increasing recognition of iCCM as a core strategy to deliver care to children, particularly those with poor access to health facilities, and reduce child mortality, in the context of the drive to achieve the Millennium Development Goals. Twenty–eight countries in sub–Saharan Africa are now the site of delivery of community case management for each of pneumonia, diarrhoea and malaria, albeit at widely differing levels of coverage between countries. Despite this progress, there are significant remaining obstacles to realizing the potential of iCCM to provide effective coverage of interventions for childhood illness at scale and quality. Here we review current trends in policy and financing of iCCM in sub–Saharan Africa to highlight two key issues: sustainable financing of iCCM, particularly from domestic sources, and the integration of iCCM in national health systems. We conclude by providing suggestions for how to move forward on these linked challenges

Integrated community case management of childhood illness in low- and middle-income countries

BACKGROUND: The leading causes of mortality globally in children younger than five years of age (under-fives), and particularly in the regions of subSaharan Africa (SSA) and Southern Asia, in 2018 were infectious diseases, including pneumonia (15%), diarrhoea (8%), malaria (5%) and newborn sepsis (7%) (UNICEF 2019). Nutrition-related factors contributed to 45% of under-five deaths (UNICEF 2019). World Health Organization (WHO) and United Nations Children's Fund (UNICEF), in collaboration with other development partners, have developed an approach – now known as integrated community case management (iCCM) – to bring treatment services for children 'closer to home'. The iCCM approach provides integrated case management services for two or more illnesses – including diarrhoea, pneumonia, malaria, severe acute malnutrition or neonatal sepsis – among under-fives at community level (i.e. outside of healthcare facilities) by lay health workers where there is limited access to health facility-based case management services (WHO/UNICEF 2012). OBJECTIVES: To assess the eHects of the integrated community case management (iCCM) strategy on coverage of appropriate treatment for childhood illness by an appropriate provider, quality of care, case load or severity of illness at health facilities, mortality, adverse events and coverage of careseeking for children younger than five years of age in low- and middle-income countries. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL on 7 November 2019, Virtual Health Library on 8 November 2019, and Popline on 5 December 2018, three other databases on 22 March 2019 and two trial registers on 8 November 2019. We performed reference checking, and citation searching, and contacted study authors to identify additional studies.http://www.thecochranelibrary.compm2021Statistic