Bioterrorism-Related Anthrax: International Response by the Centers for Disease Control and Prevention

After reports of the intentional release of Bacillus anthracis in the United States, epidemiologists, laboratorians, and clinicians around the world were called upon to respond to widespread political and public concerns. To respond to inquiries from other countries regarding anthrax and bioterrorism, the Centers for Disease Control and Prevention established an international team in its Emergency Operations Center. From October 12, 2001, to January 2, 2002, this team received 130 requests from 70 countries and 2 territories. Requests originated from ministries of health, international organizations, and physicians and included subjects ranging from laboratory procedures and clinical evaluations to assessments of environmental and occupational health risks. The information and technical support provided by the international team helped allay fears, prevent unnecessary antibiotic treatment, and enhance laboratory-based surveillance for bioterrorism events worldwide

Young at risk-people in Maputo City, Mozambique, present a high willingness to participate in HIV trials: Results from an HIV vaccine preparedness cohort study

Introduction: Vaccine efficacy testing requires engagement of willing volunteers with high disease incidence. We evaluated factors associated with willingness to participate in potential future HIV vaccine trials in Maputo, Mozambique. Methods: Adults aged 18–35 years without HIV and who reported at least two sexual partners in the 3 months prior to screening were enrolled into a 24-month observational study. They were asked at screening and exit if they would be willing to participate in a theoretical HIV vaccine study. Bivariate and multivariate logistic regression analyses were done between willingness to participate, demographic, sexual behavior, and motivational factors for screening visit data. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with willingness to participate for data from both visits. Results: A total of 577 participants without HIV were eligible, including 275 (48%) women. The mean age was 22.2 (SD ± 3.9) years. At screening 529 (92%) expressed willingness to participate and the proportion remained stable at 378 (88%) of the 430 participants retained through the exit visit (p = 0.209). Helping the country (n = 556) and fear of needles (n = 26) were the top motive and barrier for willingness to participate, respectively. Results from the GEE binary logistic regression (screening visit and exit visit) showed that wanting to learn how to avoid risk behaviors (aOR 3.33, 95% CI: 1.61–6.86) and feeling protected against HIV infection (aOR 2.24, 95% CI: 1.07–4.7) were associated with willingness to participate in HIV vaccine studies. Conclusion: The majority of our study population in Mozambique expressed willingness to participate in a theoretical HIV vaccine trial. Participation in a HIV vaccine trial was seen as a way to contribute to the fight against HIV but was associated with some unrealistic expectations such as protection against HIV. This reinforces the need for continuous mobilization and awareness of potential participants to HIV vaccine trial

Persons living with HIV in sero-discordant partnerships experience improved HIV care engagement compared with persons living with HIV in sero-concordant partnerships: a cross-sectional analysis of four African countries

Background Persons living with HIV (PLWH) who are members of sero-discordant and sero-concordant relationships may experience psychological stressors or motivators that affect HIV care. We assessed the association between sero-discordance status, antiretroviral therapy (ART) uptake, and viral suppression in the African Cohort Study (AFRICOS). Methods AFRICOS enrolls PLWH and HIV-uninfected individuals at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. At enrollment, we determined ART use through self-report. Viral suppression was defined as HIV RNA < 1000 copies/mL. We analyzed PLWH who were index participants within two types of sexual dyads: sero-discordant or sero-concordant. Binomial regression models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ART use and viral suppression at study enrollment. Results From January 2013 through March 2018, 223 index participants from sero-discordant dyads and 61 from sero-concordant dyads were enrolled. The majority of the indexes were aged 25–34 years (50.2%), female (53.4%), and married (96.5%). Sero-discordant indexes were more likely to disclose their status to partners compared with sero-concordant indexes (96.4% vs. 82.0%, p < 0.001). After adjustment, sero-discordant index participants were more likely to be on ART (aPR 2.8 [95% CI 1.1–6.8]), but no more likely to be virally suppressed. Results may be driven by unique psycho-social factors and global implementation of treatment as prevention. Conclusions PLWH in sero-discordant sexual partnerships demonstrated improved uptake of ART compared with those in sero-concordant partnerships. Interventions are needed to increase care engagement by individuals in sero-concordant relationships to improve HIV outcomes

Pathway-Based Evaluation in Early Onset Colorectal Cancer Suggests Focal Adhesion and Immunosuppression along with Epithelial-Mesenchymal Transition

Colorectal cancer (CRC) has one of the highest incidences among all cancers. The majority of CRCs are sporadic cancers that occur in individuals without family histories of CRC or inherited mutations. Unfortunately, whole-genome expression studies of sporadic CRCs are limited. A recent study used microarray techniques to identify a predictor gene set indicative of susceptibility to early-onset CRC. However, the molecular mechanisms of the predictor gene set were not fully investigated in the previous study. To understand the functional roles of the predictor gene set, in the present study we applied a subpathway-based statistical model to the microarray data from the previous study and identified mechanisms that are reasonably associated with the predictor gene set. Interestingly, significant subpathways belonging to 2 KEGG pathways (focal adhesion; natural killer cell-mediated cytotoxicity) were found to be involved in the early-onset CRC patients. We also showed that the 2 pathways were functionally involved in the predictor gene set using a text-mining technique. Entry of a single member of the predictor gene set triggered a focal adhesion pathway, which confers anti-apoptosis in the early-onset CRC patients. Furthermore, intensive inspection of the predictor gene set in terms of the 2 pathways suggested that some entries of the predictor gene set were implicated in immunosuppression along with epithelial-mesenchymal transition (EMT) in the early-onset CRC patients. In addition, we compared our subpathway-based statistical model with a gene set-based statistical model, MIT Gene Set Enrichment Analysis (GSEA). Our method showed better performance than GSEA in the sense that our method was more consistent with a well-known cancer-related pathway set. Thus, the biological suggestion generated by our subpathway-based approach seems quite reasonable and warrants a further experimental study on early-onset CRC in terms of dedifferentiation or differentiation, which is underscored in EMT and immunosuppression

Large-scale unit commitment under uncertainty: an updated literature survey

The Unit Commitment problem in energy management aims at finding the optimal production schedule of a set of generation units, while meeting various system-wide constraints. It has always been a large-scale, non-convex, difficult problem, especially in view of the fact that, due to operational requirements, it has to be solved in an unreasonably small time for its size. Recently, growing renewable energy shares have strongly increased the level of uncertainty in the system, making the (ideal) Unit Commitment model a large-scale, non-convex and uncertain (stochastic, robust, chance-constrained) program. We provide a survey of the literature on methods for the Uncertain Unit Commitment problem, in all its variants. We start with a review of the main contributions on solution methods for the deterministic versions of the problem, focussing on those based on mathematical programming techniques that are more relevant for the uncertain versions of the problem. We then present and categorize the approaches to the latter, while providing entry points to the relevant literature on optimization under uncertainty. This is an updated version of the paper "Large-scale Unit Commitment under uncertainty: a literature survey" that appeared in 4OR 13(2), 115--171 (2015); this version has over 170 more citations, most of which appeared in the last three years, proving how fast the literature on uncertain Unit Commitment evolves, and therefore the interest in this subject

Ebola policies that hinder epidemic response by limiting scientific discourse

Copyright © 2015 by The American Society of Tropical Medicine and Hygiene. There is an unprecedented epidemic of Ebola virus disease (EVD) in west Africa. There has been a strong response from dedicated health professionals. However, there have also been irrational and fear-based responses that have contributed to misallocation of resources, stigma, and deincentivizing volunteers to combat Ebola at its source. Recently, the State of Louisiana Department of Health and Hospitals issued a ban on those coming from affected countries wishing to attend the annual meetings of American Society of Tropical Medicine and Hygiene and the American Public Health Association, both of which were held in New Orleans. We argue against such policies, question evidence and motivations, and discuss their practical and ethical implications in hampering effective responses to EVD by the scientific community. We aim to shed light on this issue and its implications for the future of public health interventions, reflect on the responsibility of health providers and professional societies as advocates for patients and the public health, and call for health professionals and societies to work to challenge inappropriate political responses to public health crises

Hepatitis and tuberculosis testing are much less common than HIV testing among adults in Kisumu, Kenya: results from a cross-sectional assessment

Abstract Background Kenya has a high burden of HIV, viral hepatitis, and tuberculosis. Screening is necessary for early diagnosis and treatment, which reduces morbidity and mortality across all three illnesses. We evaluated testing uptake for HIV, viral hepatitis, and tuberculosis in Kisumu, Kenya. Methods Cross-sectional data from adults aged 18–35 years who enrolled in a prospective HIV incidence cohort study from February 2017 to May 2018 were analyzed. A questionnaire was administered to each participant at screening for study eligibility to collect behavioral characteristics and to assess prior testing practices. Among participants without a history of previously-diagnosed HIV, multivariable robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for factors potentially associated with HIV testing in the 12 months prior to enrollment. A hierarchical model was used to test for differential access to testing due to spatial location. Results Of 671 participants, 52 (7.7%) were living with HIV, 308 (45.9%) were female, and the median age was 24 (interquartile range 21–28) years. Among 651 (97.0%) who had ever been tested for HIV, 400 (61.2%) reported HIV testing in the past 6 months, 129 (19.7%) in the past 6–12 months, and 125 (19.1%) more than one year prior to enrollment. Any prior testing for viral hepatitis was reported by 8 (1.2%) participants and for tuberculosis by 51 (7.6%). In unadjusted models, HIV testing in the past year was more common among females (PR 1.08 [95% CI 1.01, 1.17]) and participants with secondary education or higher (PR 1.10 [95% CI 1.02, 1.19]). In the multivariable model, only secondary education or higher was associated with recent HIV testing (adjusted PR 1.10 [95% CI 1.02, 1.20]). Hierarchical models showed no geographic differences in HIV testing across Kisumu subcounties. Conclusions Prior HIV testing was common among study participants and most had been tested within the past year but testing for tuberculosis and viral hepatitis was far less common. HIV testing gaps exist for males and those with lower levels of education. HIV testing infrastructure could be leveraged to increase access to testing for other endemic infectious diseases

Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial

<div><p>Background</p><p>Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings.</p><p>Methods and Findings</p><p>Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥18 mo with CD4 count > 350 cells/mm³ in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression.</p><p>Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52–3.38; <i>p <</i> 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52–241.02; <i>p</i> = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82–2.27, and IRR = 1.43, 95% CI 0.54–3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.</p><p>Conclusions</p><p>CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX guidelines.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01425073" target="_blank">NCT01425073</a></p></div