A preliminary study of genetic factors that influence susceptibility to bovine tuberculosis in the British cattle herd

Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test (‘reactors’). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling

Islands Within Islands: Bacterial Phylogenetic Structure and Consortia in Hawaiian Lava Caves and Fumaroles

Lava caves, tubes, and fumaroles in Hawai‘i present a range of volcanic, oligotrophic environments from different lava flows and host unexpectedly high levels of bacterial diversity. These features provide an opportunity to study the ecological drivers that structure bacterial community diversity and assemblies in volcanic ecosystems and compare the older, more stable environments of lava tubes, to the more variable and extreme conditions of younger, geothermally active caves and fumaroles. Using 16S rRNA amplicon-based sequencing methods, we investigated the phylogenetic distinctness and diversity and identified microbial interactions and consortia through co-occurrence networks in 70 samples from lava tubes, geothermal lava caves, and fumaroles on the island of Hawai‘i. Our data illustrate that lava caves and geothermal sites harbor unique microbial communities, with very little overlap between caves or sites. We also found that older lava tubes (500–800 yrs old) hosted greater phylogenetic diversity (Faith's PD) than sites that were either geothermally active or younger (<400 yrs old). Geothermally active sites had a greater number of interactions and complexity than lava tubes. Average phylogenetic distinctness, a measure of the phylogenetic relatedness of a community, was higher than would be expected if communities were structured at random. This suggests that bacterial communities of Hawaiian volcanic environments are phylogenetically over-dispersed and that competitive exclusion is the main driver in structuring these communities. This was supported by network analyses that found that taxa (Class level) co-occurred with more distantly related organisms than close relatives, particularly in geothermal sites. Network “hubs” (taxa of potentially higher ecological importance) were not the most abundant taxa in either geothermal sites or lava tubes and were identified as unknown families or genera of the phyla, Chloroflexi and Acidobacteria. These results highlight the need for further study on the ecological role of microbes in caves through targeted culturing methods, metagenomics, and long-read sequence technologies

Determination of freedom-from-rabies for small Indian mongoose populations in the United States Virgin Islands, 2019–2020

Mongooses, a nonnative species, are a known reservoir of rabies virus in the Caribbean region. A cross-sectional study of mongooses at 41 field sites on the US Virgin Islands of St. Croix, St. John, and St. Thomas captured 312 mongooses (32% capture rate). We determined the absence of rabies virus by antigen testing and rabies virus exposure by antibody testing in mongoose populations on all three islands. USVI is the first Caribbean state to determine freedom-from-rabies for its mongoose populations with a scientifically-led robust cross-sectional study. Ongoing surveillance activities will determine if other domestic and wildlife populations in USVI are rabies-free

Effect of Peer Health Workers on AIDS Care in Rakai, Uganda: A Cluster-Randomized Trial

Human resource limitations are a challenge to the delivery of antiretroviral therapy (ART) in low-resource settings. We conducted a cluster randomized trial to assess the effect of community-based peer health workers (PHW) on AIDS care of adults in Rakai, Uganda.15 AIDS clinics were randomized 2:1 to receive the PHW intervention (n = 10) or control (n = 5). PHW tasks included clinic and home-based provision of counseling, clinical, adherence to ART, and social support. Primary outcomes were adherence and cumulative risk of virologic failure (>400 copies/mL). Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART. Analysis was by intention to treat. From May 2006 to July 2008, 1336 patients were followed. 444 (33%) of these patients were already on ART at the start of the study. No significant differences were found in lack of adherence (<95% pill count adherence risk ratio [RR] 0.55, 95% confidence interval [CI] 0.23-1.35; <100% adherence RR 1.10, 95% CI 0.94-1.30), cumulative risk of virologic failure (RR 0.81, 95% CI 0.61-1.08) or in shorter-term virologic outcomes (24 week virologic failure RR 0.93, 95% CI 0.65-1.32; 48 week, RR 0.83, 95% CI 0.47-1.48; 72 week, RR 0.81, 95% CI 0.44-1.49). However, virologic failure rates >or=96 weeks into ART were significantly decreased in the intervention arm compared to the control arm (96 week failure RR 0.50, 95% CI 0.31-0.81; 120 week, RR 0.59, 95% CI 0.22-1.60; 144 week, RR 0.39, 95% CI 0.16-0.95; 168 week, RR 0.30, 95% CI 0.097-0.92; 192 week, RR 0.067, 95% CI 0.0065-0.71).A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART, but did not affect cumulative risk of virologic failure, adherence measures, or shorter-term virologic outcomes. PHWs may be an effective intervention to sustain long-term ART in low-resource settings.ClinicalTrials.gov NCT00675389

Mongooses (\u3ci\u3eUrva auropunctata\u3c/i\u3e) as reservoir hosts of leptospira species in the United States Virgin Islands, 2019–2020

During 2019–2020, the Virgin Islands Department of Health investigated potential animal reservoirs of Leptospira spp., the bacteria that cause leptospirosis. In this cross-sectional study, we investigated Leptospira spp. exposure and carriage in the small Indian mongoose (Urva auropunctata, syn: Herpestes auropunctatus), an invasive animal species. This study was conducted across the three main islands of the U.S. Virgin Islands (USVI), which are St. Croix, St. Thomas, and St. John. We used the microscopic agglutination test (MAT), fluorescent antibody test (FAT), real-time polymerase chain reaction (lipl32 rt-PCR), and bacterial culture to evaluate serum and kidney specimens and compared the sensitivity, specificity, positive predictive value, and negative predictive value of these laboratory meth-ods. Mongooses (n = 274) were live-trapped at 31 field sites in ten regions across USVI and humanely euthanized for Leptospira spp. testing. Bacterial isolates were sequenced and evaluated for species and phylogenetic analysis using the ppk gene. Anti-Leptospira spp. antibodies were detected in 34% (87/256) of mongooses. Reactions were observed with the following serogroups: Sejroe, Icterohaemorrhagiae, Pyrogenes, Mini, Cynopteri, Australis, Hebdomadis, Autumnalis, Mankarso, Pomona, and Ballum. Of the kidney specimens exam-ined, 5.8% (16/270) were FAT-positive, 10% (27/274) were culture-positive, and 12.4% (34/ 274) were positive by rt-PCR. Of the Leptospira spp. isolated from mongooses, 25 were L. borgpetersenii, one was L. interrogans, and one was L. kirschneri. Positive predictive values of FAT and rt-PCR testing for predicting successful isolation of Leptospira by culture were 88% and 65%, respectively. The isolation and identification of Leptospira spp. in mongooses highlights the potential role of mongooses as a wildlife reservoir of leptospirosis; mongooses could be a source of Leptospira spp. infections for other wildlife, domestic animals, and humans

Peer-based behavioral health program for drug users in China: a pilot study

<p>Abstract</p> <p>Background</p> <p>Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked.</p> <p>Methods</p> <p>A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up).</p> <p>Results</p> <p>Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline.</p> <p>Conclusions</p> <p>This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.</p

Peer-based behavioral health program for drug users in China: a pilot study

<p>Abstract</p> <p>Background</p> <p>Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked.</p> <p>Methods</p> <p>A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up).</p> <p>Results</p> <p>Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline.</p> <p>Conclusions</p> <p>This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.</p

Toward community standards and software for whole-cell modeling

Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate, comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance:We anticipate that these new standards and software will enable more comprehensive models

Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study

Background: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. Findings: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from &lt;5% of those younger than 20 years to &gt;66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from &lt;1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. Interpretation: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds. Funding: UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations