Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: An observational and genomic study.

Background: Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle. Methods: We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010 to 2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba Island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data, we inferred transmission chains and estimated case detection. Using a decision tree model, we quantified the public health burden and evaluated the impact and cost-effectiveness of interventions over a 10-year time horizon. Results: We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were projected to be highly cost-effective ($256 per death averted), only dog vaccination interrupts transmission. A combined One Health approach of routine annual dog vaccination together with free post-exposure vaccines for bite victims, rapidly eliminates rabies, is highly cost-effective ($1657 per death averted) and by maintaining rabies freedom prevents over 30 families from suffering traumatic rabid dog bites annually on Pemba island. Conclusions: A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable, and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere. Funding: Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, the Department of Health and Human Services of the National Institutes of Health [R01AI141712] and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa's Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z], Royal Society of Tropical Medicine and Hygiene Small Grant 2017 [GR000892] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation [OPP49679]. Whole-genome sequencing was partially supported from APHA by funding from the UK Department for Environment, Food and Rural Affairs (Defra), Scottish government and Welsh government under projects SEV3500 and SE0421.

Classification and characterisation of livestock production systems in northern Tanzania.

Livestock keepers in sub-Saharan Africa face a range of pressures, including climate change, land loss, restrictive policies, and population increase. Widespread adaptation in response can lead to the emergence of new, non-traditional typologies of livestock production. We sought to characterise livestock production systems in two administrative regions in northern Tanzania, an area undergoing rapid social, economic, and environmental change. Questionnaire and spatial data were collected from 404 livestock-keeping households in 21 villages in Arusha and Manyara Regions in 2016. Multiple factor analysis and hierarchical cluster analysis were used to classify households into livestock production systems based on household-level characteristics. Adversity-based indicators of vulnerability, including reports of hunger, illness, and livestock, land and crop losses were compared between production systems. Three distinct clusters emerged through this process. The ethnic, environmental and livestock management characteristics of households in each cluster broadly mapped onto traditional definitions of 'pastoral', 'agro-pastoral' and 'smallholder' livestock production in the study area, suggesting that this quantitative classification system is complementary to more qualitative classification methods. Our approach allowed us to demonstrate a diversity in typologies of livestock production at small spatial scales, with almost half of study villages comprising more than one production system. We also found indicators of change within livestock production systems, most notably the adoption of crop agriculture in the majority of pastoral households. System-level heterogeneities in vulnerability were evident, with agro-pastoral households most likely to report hunger and pastoral households most likely to report illness in people and livestock, and livestock losses. We demonstrate that livestock production systems can provide context for assessing household vulnerability in northern Tanzania. Policy initiatives to improve household and community well-being should recognise the continuing diversity of traditional livestock production systems in northern Tanzania, including the diversity that can exist at small spatial scales.

Development and Validation of a Controlled Pressure Method Test Protocol for Vapor Intrusion Pathway Assessment.

Controlled pressure method (CPM) testing is a building-specific diagnostic tool for vapor intrusion (VI) pathway assessment which offers advantages over traditional pathway assessment approaches. By manipulating the building pressure conditions, the CPM creates the worst-case VI impact and provides rapid insight into the type of vapor source(s). The primary barrier to general acceptance and use of this tool is the need for definitive guidance on test design parameters, such as the indoor-outdoor pressure difference (or exhaust fan flow rate), CPM test duration, exhaust fan location, and air sampling location(s) and conditions. This study focused on a systematic evaluation of each of these factors, which then led to the formulation of proposed CPM testing guidelines. The results suggest that CPM tests should be conducted with both negative and positive pressure indoor-outdoor differentials of about 10-15 Pa, and the tests should last for at least nine indoor air exchanges for negative pressure difference testing and four indoor air exchanges for positive pressure difference testing. Although exhaust fan intake sampling is sufficient to provide critical information to assess impacts during negative pressure testing, adding room-specific indoor air sampling to both negative and positive pressure difference testing can provide insight into vapor entry locations and indoor source contributions.

Long-term evaluation of the controlled pressure method for assessment of the vapor intrusion pathway.

Vapor intrusion (VI) investigations often require sampling of indoor air for evaluating occupant risks, but can be confounded by temporal variability and the presence of indoor sources. Controlled pressure methods (CPM) have been proposed as an alternative, but temporal variability of CPM results and whether they are indicative of impacts under natural conditions have not been rigorously investigated. This study is the first involving a long-term CPM test at a house having a multiyear high temporal resolution indoor air data set under natural conditions. Key observations include (a) CPM results exhibited low temporal variability, (b) false-negative results were not obtained, (c) the indoor air concentrations were similar to the maximum concentrations under natural conditions, and (d) results exceeded long-term average concentrations and emission rates under natural conditions by 1-2 orders of magnitude. Thus, the CPM results were a reliable indicator of VI occurrence and worst-case exposure regardless of day or time of year of the CPM test.

Socio-economic status is associated with epigenetic differences in the pSoBid cohort.

BACKGROUND: Epigenetic programming and epigenetic mechanisms driven by environmental factors are thought to play an important role in human health and ageing. Global DNA methylation has been postulated as an epigenetic marker for epidemiological studies as it is reflective of changes in gene expression linked to disease. How epigenetic mechanisms are affected by psychological, sociological and biological determinants of health still remains unclear. The aim of this study was to investigate the relationship between socio-economic and lifestyle factors and epigenetic status, as measured by global DNA methylation content, in the pSoBid cohort, which is characterized by an extreme socio-economic and health gradient. METHODS: DNA was extracted from peripheral blood leukocytes using the Maxwell® 16 System and Maxwell® 16 Blood DNA Purification kit (Promega, UK). Global DNA methylation was assessed using Methylamp™ Global DNA Methylation Quantification Ultra kit (Epigentek, USA). Associations between global DNA methylation and socio-economic and lifestyle factors were investigated in linear regression models. RESULTS: Global DNA hypomethylation was observed in the most socio-economically deprived subjects. Job status demonstrated a similar relationship, with manual workers having 24% lower DNA methylation content than non-manual. Additionally, associations were found between global DNA methylation content and biomarkers of cardiovascular disease (CVD) and inflammation, including fibrinogen and interleukin-6 (IL-6), after adjustment for socio-economic factors. CONCLUSIONS: This study has indicated an association between epigenetic status and socio-economic status (SES). This relationship has direct implications for population health and is reflected in further associations between global DNA methylation content and emerging biomarkers of CVD.