Advancing pathogen genomics in resource-limited settings.

Genomic sequencing has emerged as a powerful tool to enhance early pathogen detection and characterization with implications for public health and clinical decision making. Although widely available in developed countries, the application of pathogen genomics among low-resource, high-disease burden settings remains at an early stage. In these contexts, tailored approaches for integrating pathogen genomics within infectious disease control programs will be essential to optimize cost efficiency and public health impact. We propose a framework for embedding pathogen genomics within national surveillance plans across a spectrum of surveillance and laboratory capacities. We adopt a public health approach to genomics and examine its application to high-priority diseases relevant in resource-limited settings. For each grouping, we assess the value proposition for genomics to inform public health and clinical decision-making, alongside its contribution toward research and development of novel diagnostics, therapeutics, and vaccines.

Cost-effectiveness of sub-national geographically targeted vaccination programs: A systematic review.

Immunization is an essential component of national health plans. However, the growing number of new vaccine introductions, vaccination campaigns and increasing administrative costs create logistic and financial challenges, especially in resource-limited settings. Sub-national geographic targeting of vaccination programs is a potential strategy for governments to reduce the impact of infectious disease outbreaks while optimizing resource allocation and reducing costs, promoting sustainability of critically important national immunization plans. We conducted a systematic review of peer-reviewed literature to identify studies that investigated the cost-effectiveness of geographically targeted sub-national vaccination programs, either through routine immunization or supplementary immunization activities. A total of 16 studies were included in our review, covering nine diseases of interest: cholera, dengue, enterotoxigenic Escherichia coli (ETEC), hepatitis A, Japanese encephalitis, measles, rotavirus, Shigella and typhoid fever. All studies modelled cost-effectiveness of geographically targeted vaccination. Despite the variation in study design, disease focus and country context, studies generally found that in countries where a heterogenous burden of disease exists, sub-national geographic targeting of vaccination programs in areas of high disease burden was more cost-effective than a non-targeted strategy. Sensitivity analysis revealed that cost-effectiveness was most sensitive to variations in vaccine price, vaccine efficacy, mortality rate, administrative and operational costs, discount rate, and treatment costs. This systematic review identified several key characteristics related to geographic targeting of vaccination, including the vaccination strategy used, variations in modelling parameters and their impact on cost-effectiveness. Additional research and guidance is needed to support the appropriateness and feasibility of geographically targeted vaccination and to determine what country context would make this a viable complement to routine immunization programs.

Factors affecting vaccination demand in Indonesia: a secondary analysis and multimethods national assessment.

OBJECTIVES: Vaccine hesitancy remains a major barrier to immunisation coverage worldwide. We explored influence of hesitancy on coverage and factors contributing to vaccine uptake during a national measles-rubella (MR) campaign in Indonesia. DESIGN: Secondary analyses of qualitative and quantitative data sets from existing cross-sectional studies conducted during and around the campaign. METHODS: Quantitative data used in this assessment included daily coverage reports generated by health workers, district risk profiles that indicate precampaign immunisation programme performance, and reports of campaign cessation due to vaccine hesitancy. We used t-test and χ2 tests for associations. The qualitative assessment employed three parallel national and regional studies. Deductive thematic analysis examined factors for acceptance among caregivers, health providers and programme managers. RESULTS: Coverage data were reported from 6462 health facilities across 395 districts from 1 August to 31 December 2018. The average district coverage was 73%, with wide variation between districts (2%-100%). One-third of districts fell below 70% coverage thresholds. Sixty-two of 395 (16%) districts paused the campaign due to hesitancy. Coverage among districts that never paused campaign activities due to hesitancy was significantly higher than rates for districts ever-pausing the campaign (81% vs 42%; p<0.001). Precampaign adequacy of district immunisation programmes did not explain coverage gaps (p=0.210). Qualitative analysis identified acceptance enablers including using digital health monitoring and feedback systems, increasing caregiver knowledge and awareness, making immunisation social norm, effective cross-sectoral collaboration, conducive service environment and positive experiences for mothers and children. Barriers included misinformation diffusion on social media, halal-haram issues, lack of healthcare provider knowledge, negative family influences and traditions, previous poor experiences and misinformation on adverse events. CONCLUSION: Barriers to vaccine uptake contributed to coverage gaps during national MR campaign in Indonesia. A range of supply-related and demand-related strategies were identified to address hesitancy contributors. Advancing a portfolio of tailored multilevel interventions will be critical to enhance vaccine acceptance.

Prevalence of, and factors associated with anaemia in children aged 1-3 years in Aceh, Indonesia: A cross-sectional study.

Background: Child anaemia continues to represent a major public health challenge in lower-and-middle income countries. It has serious long-term consequences for child growth and development. In Indonesia, there was a 10% increase in the national prevalence of child anaemia between 2013 and 2018. Aim: This study aims to assess the prevalence of, and factors associated with anaemia among children aged one to three years in eight districts in Aceh Province, Indonesia. Methods: A cross-sectional study was conducted on a sample of 1148 mother-child dyads aged one to three years between November and December 2018. The sampling process involved a three-stage cluster sampling design using the probability proportionate to size methodology. Anaemia status was determined using haemoglobin level (Hb < 11.0 g/dL). Data were analysed using multivariable logistic regression to estimate adjusted odds ratios (aOR) and their 95% confidence intervals (95% CI) for associated factors. Results: The overall prevalence of anaemia was 76.1% (869/1142). 44.7% (510/1142) and 28.6% (327/1142) had moderate and mild anaemia, respectively. Child aged 12-24 months (aOR: 2.00, 95% CI: 1.26-3.17), not receiving routine immunisation (aOR: 2.62, 95% CI: 1.34-5.10), and maternal anaemia (aOR: 2.15, 95% CI: 1.59-2.90) were significantly associated with anaemia. Conclusion: The prevalence of anaemia among the children in this study was high, and was associated with child age, immunisation status, and maternal anaemia. These findings provide further insight into anaemia as a public health issue at a sub-national level in Indonesia and for development of targeted programmes to address associated risk factors of child anaemia.

Alarmingly High HIV Prevalence Among Adolescent and Young Men Who have Sex with Men (MSM) in Urban Indonesia.

Indonesia's HIV epidemic is concentrated among key populations. While prevalence among men who have sex with men (MSM) is high, transmission among young MSM (15-24-years-old) remains poorly understood. We conducted a respondent driven sampling survey of 211 young MSM in urban Bandung, Indonesia in 2018-2019 to estimate HIV prevalence and associated risk factors. Thirty percent of young MSM were HIV antibody positive. This is nearly 100-fold greater than Indonesia's population prevalence and sevenfold higher than average estimates for young MSM across Asia and the Pacific Region. Individual risk factors associated with HIV infection were being 20-24 years old, having a steady partner and preferring the receptive position during sex. Issues of stigma, discrimination and social exclusion were common. Few young MSM who were open with friends and family members about their sexual identity. Among those that were, close to half reported experiencing feelings of aversion from these groups. Wider structural factors that reduce social tolerance, restrict the rights of young MSM and compel concealment of sexual identity are likely to fuel high-risk behaviors and limit access to essential testing care and support services including pre-exposure prophylaxis which is not yet widely available. Urgent health, social, legal and political actions are required to respond to these factors and reduce the disproportionate contribution of young MSM to Indonesia's HIV epidemic.

Spatiotemporal Heterogeneity of Zika Virus Transmission in Indonesia: Serosurveillance Data from a Pediatric Population.

The presence of Zika virus (ZIKV) in Indonesia has been recognized since the 1970s, but its transmission dynamics there have been poorly understood. To understand more fully the geographic distribution and burden of ZIKV infection, we performed retrospective serological tests on specimens collected from asymptomatic children age 5 to 9 years old living at 30 sites in 14 provinces. Of 870 serum samples tested, 9.2% were found to be positive for anti-ZIKV antibodies, as confirmed by plaque reduction neutralization assays. This was the same overall prevalence reported previously for 1- to 4-year-old children collected at the same sites at the same time. Together with geographic differences in seroprevalence between the age groups, these data suggest that, although ZIKV might be endemic in Indonesia, its occurrence has been focal and episodic.

Digital health for real-time monitoring of a national immunisation campaign in Indonesia: a large-scale effectiveness evaluation.

OBJECTIVE: To assess the contribution of a digital health real-time monitoring platform towards the achievement of coverage targets during a national immunisation campaign in Indonesia. INTERVENTIONS: A digital health platform was introduced to facilitate real-time reporting and data visualisation. Health workers submitted reports of children immunised each day by geolocation using mobile phones. Automated reports were generated for programme managers at all levels to enable early responses to coverage gaps. METHODS: Risk profiles were generated for each district to assess precampaign immunisation programme performance. Digital health platform use and progress towards targets were monitored continuously throughout the campaign. Study outcomes were total coverage and time to achieve full (100%) coverage. Kaplan-Meier, Cox and linear regression analyses were used to estimate the associations and outcomes after adjusting for district risk profiles. A complementary qualitative assessment explored user experiences and acceptance through interviews with vaccinators and programme managers in provinces and districts selected through multistage random sampling. RESULTS: Between August and December 2018, 6462 health facilities registered to use the digital health platform across 28 provinces and 395 districts. After adjusting for precampaign district risk profile and intracampaign delays due to vaccine hesitancy, districts with greater platform utilisation demonstrated higher coverage overall (R2=0.28, p<0.0001) and a shorter interval to achieving full coverage (>75% reporting compliance; Risk Ratio 15.4, 95% CI 5.8 to 40.6). Stronger effects were observed among districts experiencing implementation delays due to vaccine hesitancy. Results from 106 key informant interviews conducted in 6 provinces and 18 districts suggest high degrees of acceptability, ease of use and satisfaction. CONCLUSION: A digital health platform introduced for real-time monitoring of a national immunisation campaign in Indonesia was feasible, well liked and associated with improved problem solving and programme performance, particularly among districts affected by vaccine hesitancy. TRIAL REGISTRATION NUMBER: ISRCTN10850448.

Achieving the Sustainable Development Goals for water and sanitation in Indonesia - Results from a five-year (2013-2017) large-scale effectiveness evaluation.

BACKGROUND: Access to safe sanitation and the elimination of open defecation are pre-conditions for improved child health and nutrition and wider achievement of the Sustainable Development Goals (SDGs). While Indonesia has a solid policy framework, the country ranks third globally in terms of numbers of people practicing open defecation. OBJECTIVES: Our aim was to assess the effectiveness of a five-year strategy to reduce open defecation through accelerating implementation of the national sanitation program across districts receiving variable levels of external support. METHODS: Among three provinces with poor sanitation program performance, districts were selected to receive one of three levels of external support. High intensity districts (n = 6) benefitted from enabling environment strengthening support including political and social mobilization, direct capacity development, and efforts to strengthen planning, budgeting, monitoring and supervision; learning districts (n = 16) benefitted from cross-district learning opportunities and political mobilization through provincial government advocacy efforts; and comparison districts (n = 58) were monitored under routine program conditions. Outcomes included open defecation free (ODF) status and new toilet facility construction and were assessed through village level monitoring systems across all districts. Negative binomial regression and multivariate analysis were used to assess associations between levels of intervention intensity and outcomes. FINDINGS: Among districts receiving high-intensity external support improvements in political commitment, planning, coordination, financing, monitoring and supervision were observed. Relative to comparison districts, high intensity districts were more likely to be ODF (aRR 4.65, CI 2.12-10.20) with greater increase in household toilet coverage (aRR 11.15 CI 1.04-119.82). Weaker non-significant associations with ODF were observed among learning districts relative to comparison districts. INTERPRETATION: Efforts to strengthen provincial and district government capacity to implement sanitation programming in Indonesia can yield substantial improvements in outcomes in a relatively short period of time.

Zika Virus Seropositivity in 1-4-Year-Old Children, Indonesia, 2014.

We assessed Zika virus seroprevalence among healthy 1-4-year-old children using a serum sample collection assembled in 2014 representing 30 urban sites across Indonesia. Of 662 samples, 9.1% were Zika virus seropositive, suggesting widespread recent Zika virus transmission and immunity. Larger studies are needed to better determine endemicity in Indonesia.

Two clusters of Plasmodium knowlesi cases in a malaria elimination area, Sabang Municipality, Aceh, Indonesia.

In malaria elimination areas, malaria cases are sporadic and consist predominantly of imported cases. Plasmodium knowlesi cases have been reported throughout Southeast Asia where long-tailed and pig-tailed macaques and Anopheles leucosphyrus group mosquitoes are sympatric. The limitation of microscopic examination to diagnose P. knowlesi is well known. In consequence, no P. knowlesi case has previously been reported from routine health facility-based case finding activities in Indonesia. This report describes two clusters of unexpected locally acquired P. knowlesi cases found in an area where Plasmodium falciparum and Plasmodium vivax infection had been eliminated in Sabang Municipality, Aceh, Indonesia. The difficulties in diagnosis and response illustrate challenges that Southeast Asian countries will increasingly face as the formerly common malaria parasites P. falciparum and P. vivax are gradually eliminated from the region.

The UN Commission on Life Saving Commodities 3 years on: global progress update and results of a multicountry assessment.

BACKGROUND: In September, 2012, the UN Commission on Life Saving Commodities (UNCoLSC) outlined a plan to expand availability and access to 13 life saving commodities. We profile global and country progress against these recommendations between 2012 and 2015. METHODS: For 12 countries in sub-Saharan Africa that were off-track to achieve the Millennium Development Goals for maternal and child survival, we reviewed key documents and reference data, and conducted interviews with ministry staff and partners to assess the status of the UNCoLSC recommendations. The RMNCH fund provided short-term catalytic financing to support country plans to advance the commodity agenda, with activities coded by UNCoLSC recommendation. Our network of technical resource teams identified, addressed, and monitored progress against cross-cutting commodity-related challenges that needed coordinated global action. FINDINGS: In 2014 and 2015, child and maternal health commodities had fewer bottlenecks than reproductive and neonatal commodities. Common bottlenecks included regulatory challenges (ten of 12 countries); poor quality assurance (11 of 12 countries); insufficient staff training (more than half of facilities on average); and weak supply chains systems (11 of 12 countries), with stock-outs of priority commodities in about 40% of facilities on average. The RMNCH fund committed US$175·7 million to 19 countries to support strategies addressing crucial gaps. $68·2 million (39·0%) of the funds supported systems-strengthening interventions with the remainder split across reproductive, maternal, newborn, and child health. Health worker training ($88·6 million, 50·4%), supply chain ($53·3 million, 30·0%), and demand generation ($21·1 million, 12·0%) were the major topics of focus. All priority commodities are now listed in the WHO Essential Medicines List; appropriate price reductions were secured; quality manufacturing was improved; a fast-track registration mechanism for prequalified products was established; and methods were developed for advocacy, quantification, demand generation, supply chain, and provider training. Slower progress was evident around regulatory harmonisation and quality assurance. INTERPRETATION: Much work is needed to achieve full implementation of the UNCoLSC recommendations. Coordinated efforts to secure price reductions beyond the 13 commodities and improve regulatory efficiency, quality, and supply chains are still needed alongside broader dissemination of work products. FUNDING: Governments of Norway (NORAD) and the UK (DFID).

The Effect of Community-Based Prevention and Care on Ebola Transmission in Sierra Leone.

OBJECTIVES: To examine the acceptability, use, effects on early isolation, and contribution to Ebola virus disease (EVD) transmission of Community Care Centers (CCCs), which were rapidly deployed in Sierra Leone during an accelerated phase of the 2014-2015 EVD epidemic. METHODS: Focus group discussions, triads, and key informant interviews assessed acceptability of the CCCs. Facility registers, structured questionnaires, and laboratory records documented use, admission, and case identification. We estimated transmission effects by comparing time between symptom onset and isolation at CCCs relative to other facilities with the national Viral Hemorrhagic Fever data set. RESULTS: Between November 2014 and January 2015, 46 CCCs were operational. Over 13 epidemic weeks, 6129 patients were triaged identifying 719 (12%) EVD suspects. Community acceptance was high despite initial mistrust. Nearly all patients presented to CCCs outside the national alert system. Isolation of EVD suspects within 4 days of symptoms was higher in CCCs compared with other facilities (85% vs 49%; odds ratio = 6.0; 95% confidence interval = 4.0, 9.1), contributing to a 13% to 32% reduction in the EVD reproduction number (Ro). CONCLUSIONS: Community-based approaches to prevention and care can reduce Ebola transmission.

The effect of an integrated multisector model for achieving the Millennium Development Goals and improving child survival in rural sub-Saharan Africa: a non-randomised controlled assessment.

BACKGROUND: Simultaneously addressing multiple Millennium Development Goals (MDGs) has the potential to complement essential health interventions to accelerate gains in child survival. The Millennium Villages project is an integrated multisector approach to rural development operating across diverse sub-Saharan African sites. Our aim was to assess the effects of the project on MDG-related outcomes including child mortality 3 years after implementation and compare these changes to local comparison data. METHODS: Village sites averaging 35,000 people were selected from rural areas across diverse agroecological zones with high baseline levels of poverty and undernutrition. Starting in 2006, simultaneous investments were made in agriculture, the environment, business development, education, infrastructure, and health in partnership with communities and local governments at an annual projected cost of US$120 per person. We assessed MDG-related progress by monitoring changes 3 years after implementation across Millenium Village sites in nine countries. The primary outcome was the mortality rate of children younger than 5 years of age. To assess plausibility and attribution, we compared changes to reference data gathered from matched randomly selected comparison sites for the mortality rate of children younger than 5 years of age. Analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT01125618. FINDINGS: Baseline levels of MDG-related spending averaged $27 per head, increasing to $116 by year 3 of which $25 was spent on health. After 3 years, reductions in poverty, food insecurity, stunting, and malaria parasitaemia were reported across nine Millennium Village sites. Access to improved water and sanitation increased, along with coverage for many maternal-child health interventions. Mortality rates in children younger than 5 years of age decreased by 22% in Millennium Village sites relative to baseline (absolute decrease 25 deaths per 1000 livebirths, p=0·015) and 32% relative to matched comparison sites (30 deaths per 1000 livebirths, p=0·033). INTERPRETATION: An integrated multisector approach for addressing the MDGs can produce rapid declines in child mortality in the first 3 years of a long-term effort in rural sub-Saharan Africa. FUNDING: UN Human Security Trust Fund, the Lenfest Foundation, Bill & Melinda Gates Foundation, and Becton Dickinson.