Factors associated with depressive symptoms among returnee migrants and non-migrants working adults in Madi municipality in Nepal: a community-based cross-sectional study.

BACKGROUND: Mental health is a growing concern worldwide. It is not well understood whether international labour migrants from Nepal who return to Nepal are at higher risk of developing mental health problems. The purpose of our study was to determine the prevalence of and examine the associated factors for depressive symptoms among returnee migrants and non-migrant working male adults in Nepal. METHODS: A cross-sectional survey of a probability-based sample of 725 participants was conducted in February 2020. The sample was comprised of two groups based on migration status: returning migrants and non-migrants. The 21-item Beck Depression Inventory (BDI-21) questionnaire was used to assess depressive symptoms. Logistic regression was applied to investigate factors associated with symptoms of depression. RESULTS: The overall prevalence of depressive symptoms was 10.1%. However, the prevalence of depressive symptoms was lower (7%) among returnee migrants compared to non-migrants (13.7%). Men in the lower income group had a higher chance of having depressive (AOR = 5.88, 95% CI: 2.17-15.96) than those in the higher income group. Similarly, Buddhists and Christians were more likely to be depressed (AOR = 2.20, 95% CI: 1.03-4.68) than Hindus. Participants with more than two children had a higher chance of having of depressive symptoms (AOR = 4.80, 95% CI: 1.15-20.05) compared with those without children. Unmarried men were more likely to be depressed (AOR = 4.07, 95%, CI:1.11-14.92) than those who were married. CONCLUSION: The working Nepali adult male population in Nepal, including returning migrants, is at risk of depressive symptoms, but this association was lower in those in the higher income group, returnee migrants, those who were married, Hindus and those with no children. Our results highlight the need to monitor and develop national policies to ensure the mental health of the Nepali male adult population, including returnee migrants.

Masks During Pandemics Caused by Respiratory Pathogens-Evidence and Implications for Action.

Importance: As demonstrated by the influenza virus and SARS-CoV-2, viruses spread by the respiratory route can cause deadly pandemics, and face masks can reduce the spread of these pathogens. The effectiveness of responses to future epidemics and pandemics will depend at least in part on whether evidence on masks, including from the COVID-19 pandemic, is utilized. Observations: Well-designed observational studies have demonstrated the association of mask use with reduced transmission of SARS-CoV-2 in community settings, and rigorous evaluations of mask mandates have found substantial protection. Disagreement about whether face masks reduce the spread of SARS-CoV-2 has been exacerbated by a focus on randomized trials, which are limited in number, scope, and statistical power. Many effective public health policies have never been assessed in randomized clinical trials; such trials are not the gold standard of evidence for the efficacy of all interventions. Masking in the community to reduce the spread of SARS-CoV-2 is supported by robust evidence from diverse settings and populations. Data on the epidemiologic, environmental, and mask design parameters that influence the effectiveness of masking provide insights on when and how masks should be used to prevent transmission. Conclusions and Relevance: During the next epidemic or pandemic caused by a respiratory pathogen, decision-makers will need to rely on existing evidence as they implement interventions. High-quality studies have shown that use of face masks in the community is associated with reduced transmission of SARS-CoV-2 and is likely to be an important component of an effective response to a future respiratory threat.

Monitoring SARS-CoV-2 incidence and seroconversion among university students and employees: a longitudinal cohort study in California, June-August 2020.

OBJECTIVES: To identify incident SARS-CoV-2 infections and inform effective mitigation strategies in university settings, we piloted an integrated symptom and exposure monitoring and testing system among a cohort of university students and employees. DESIGN: Prospective cohort study. SETTING: A public university in California from June to August 2020. PARTICIPANTS: 2180 university students and 738 university employees. PRIMARY OUTCOME MEASURES: At baseline and endline, we tested participants for active SARS-CoV-2 infection via quantitative PCR (qPCR) test and collected blood samples for antibody testing. Participants received notifications to complete additional qPCR tests throughout the study if they reported symptoms or exposures in daily surveys or were selected for surveillance testing. Viral whole genome sequencing was performed on positive qPCR samples, and phylogenetic trees were constructed with these genomes and external genomes. RESULTS: Over the study period, 57 students (2.6%) and 3 employees (0.4%) were diagnosed with SARS-CoV-2 infection via qPCR test. Phylogenetic analyses revealed that a super-spreader event among undergraduates in congregate housing accounted for at least 48% of cases among study participants but did not spread beyond campus. Test positivity was higher among participants who self-reported symptoms (incidence rate ratio (IRR) 12.7; 95% CI 7.4 to 21.8) or had household exposures (IRR 10.3; 95% CI 4.8 to 22.0) that triggered notifications to test. Most (91%) participants with newly identified antibodies at endline had been diagnosed with incident infection via qPCR test during the study. CONCLUSIONS: Our findings suggest that integrated monitoring systems can successfully identify and link at-risk students to SARS-CoV-2 testing. As the study took place before the evolution of highly transmissible variants and widespread availability of vaccines and rapid antigen tests, further research is necessary to adapt and evaluate similar systems in the present context.

Association between epidemiologic case definition categories and adverse clinical outcome in patients with Clostridiodes difficile infection in San Francisco County, California: a five-year retrospective cohort study.

BACKGROUND: Understanding the predictors of adverse clinical outcomes following incident Clostridiodes difficile infection (CDI) can help clinicians identify which patients are at risk of complications and help prioritize the provision of their care. In this study, we assessed the associations between epidemiologic case definition categories and adverse clinical outcomes in patients with CDI in San Francisco County, California. METHODS: We conducted a retrospective cohort study using CDI surveillance data (n = 3274) from the California Emerging Infections Program for the time period 2016 to 2020. After independent associations were established, two multivariable logistic and log-binomial regression models were constructed for the final statistical analysis. RESULT: The mean cumulative incidence of CDI cases was 78.8 cases per 100,000 population. The overall recurrence rate and the 30-day all-cause mortality rate were 11.1% and 4.5%, respectively. After adjusting for potential confounders, compared to the community associated CDI cases, healthcare facility onset (AOR = 3.1; 95% CI [1.3-7]) and community-onset-healthcare facility associated (AOR = 2.4; 95% CI [1.4-4.3]) CDI cases were found to have higher odds of all-cause 30-day mortality. Community onset-healthcare facility-associated CDI case definition category was found to be significantly associated with an increased risk of recurrence of CDI (ARR = 1.7; 95% CI [1.2-2.4]). CONCLUSION: Although the incidence of community-associated CDI cases has been rising, the odds of all-cause 30-day mortality and the risk of recurrent CDI associated with these infections are lower than healthcare facility onset and community-onset healthcare facility-associated CDI cases.

Impact of Pneumococcal Conjugate Vaccines on Antibiotic-Nonsusceptible Invasive Pneumococcal Disease in the United States.

BACKGROUND: Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States after introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD. METHODS: We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100 000 persons). RESULTS: From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, whereas incidence of nonvaccine type (NVT) NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-2018, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes. CONCLUSIONS: Nonsusceptible IPD incidence decreased after PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD.

Rates of respiratory syncytial virus (RSV)-associated hospitalization among adults with congestive heart failure-United States, 2015-2017.

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. METHODS: Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (<65 years and ≥65 years) RSV-associated hospitalization rates by CHF status. Estimates were adjusted for age and the under-detection of RSV. We also report rate differences (RD) and rate ratios (RR) by comparing the rates for those with and without CHF. RESULTS: 2042 hospitalized RSV cases with CHF status recorded were identified. Most (60.2%, n = 1230) were ≥65 years, and 28.3% (n = 577) had CHF. The adjusted RSV hospitalization rate was 26.7 (95% CI: 22.2, 31.8) per 10,000 population in adults with CHF versus 3.3 (95% CI: 3.3, 3.3) per 10,000 in adults without CHF (RR: 8.1, 95% CI: 6.8, 9.7; RD: 23.4, 95% CI: 18.9, 28.5). Adults with CHF had higher rates of RSV-associated hospitalization in both age groups (<65 years and ≥65 years). Adults ≥65 years with CHF had the highest rate (40.5 per 10,000 population, 95% CI: 35.1, 46.6). CONCLUSIONS: Adults with CHF had 8 times the rate of RSV-associated hospitalization compared with adults without CHF. Identifying high-risk populations for RSV infection can inform future RSV vaccination policies and recommendations.

Feasibility and effectiveness of daily temperature screening to detect COVID-19 in a prospective cohort at a large public university.

BACKGROUND: Many persons with active SARS-CoV-2 infection experience mild or no symptoms, presenting barriers to COVID-19 prevention. Regular temperature screening is nonetheless used in some settings, including university campuses, to reduce transmission potential. We evaluated the potential impact of this strategy using a prospective university-affiliated cohort. METHODS: Between June and August 2020, 2912 participants were enrolled and tested for SARS-CoV-2 by PCR at least once (median: 3, range: 1-9). Participants reported temperature and symptoms daily via electronic survey using a previously owned or study-provided thermometer. We assessed feasibility and acceptability of daily temperature monitoring, calculated sensitivity and specificity of various fever-based strategies for restricting campus access to reduce transmission, and estimated the association between measured temperature and SARS-CoV-2 test positivity using a longitudinal binomial mixed model. RESULTS: Most participants (70.2%) did not initially have a thermometer for taking their temperature daily. Across 5481 total person months, the average daily completion rate of temperature values was 61.6% (median: 67.6%, IQR: 41.8-86.2%). Sensitivity for SARS-CoV-2 ranged from 0% (95% CI 0-9.7%) to 40.5% (95% CI 25.6-56.7%) across all strategies for self-report of possible COVID-19 symptoms on day of specimen collection, with corresponding specificity of 99.9% (95% CI 99.8-100%) to 95.3% (95% CI 94.7-95.9%). An increase of 0.1 °F in individual mean body temperature on the same day as specimen collection was associated with 1.11 increased odds of SARS-CoV-2 positivity (95% CI 1.06-1.17). CONCLUSIONS: Our study is the first, to our knowledge, that examines the feasibility, acceptability, and effectiveness of daily temperature screening in a prospective cohort during an infectious disease outbreak, and the only study to assess these strategies in a university population. Daily temperature monitoring was feasible and acceptable; however, the majority of potentially infectious individuals were not detected by temperature monitoring, suggesting that temperature screening is insufficient as a primary means of detection to reduce transmission of SARS-CoV-2.

Acute myocardial infarction associated with abacavir and tenofovir based antiretroviral drug combinations in the United States.

INTRODUCTION: Although individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations. METHODS: Using an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients. RESULTS: Over 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4-16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27-2.88), abacavir-lamivudine-atazanavir (1.58; 1.08-2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07-1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54-0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir. CONCLUSION: The antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.

Predictive variables for hemodialysis and death in Japanese spotted fever, and the association between distance from rivers and incidence.

The number of patients with Japanese spotted fever (JSF) and its case fatality rate have been increasing in Japan and other East Asian countries. Better clinical and laboratory biomarkers are needed to avoid misdiagnosing JSF and to predict severe cases. In addition to determining these predictors, we aimed to examine the association between the incidence of JSF and the distance from rivers, in Hiroshima Prefecture, one of the most JSF prevalent areas in Japan. Patients diagnosed with JSF from 2009 to 2017 in two hospitals in Onomichi City in Hiroshima Prefecture were studied, and their clinical characteristics and laboratory data were collected retrospectively from medical charts. A random forest was used to identify predictors of severe JSF leading to hemodialysis or death. A multivariable negative binomial regression model was utilized to analyze the association between the cumulative incidence in each postal code area and the distance from the residential postal code area to the closest river. Out of 82 patients with JSF (mean age at diagnosis, 74.1 ± 10.6 years; 34 (41.5 %) men), 6 cases were regarded as severe (among them 5 hemodialysis patients and 3 deaths). Twenty-eight (34.1 %) patients were misdiagnosed at least once at the initial hospital visit. Laboratory examination showed 34.5 % had atypical lymphocytes, 73.8 % had no eosinophils, 75.6 % had an elevated aspartate aminotransferase (AST) level, and 69.5 % had hyponatremia. Among cases without urine leucocytes, 63.3 % had proteinuria and 63.3 % had hematuria. Low serum total protein was the strongest predictor of severe JSF, followed by high blood urea nitrogen (BUN) and low albumin. Geospatial analysis showed a significant negative association between the cumulative incidence of JSF cases and the distance from rivers in an adjusted model: the cumulative incidence decreased by 0.51 times (95 % CI: 0.30 to 0.86) for every kilometer of distance from the residential postal code area to the closest river. Some laboratory data may be useful in averting misdiagnosis of JSF and in predicting severe cases. Additional studies should be done in order to clarify the mechanism and association of the incidence of JSF with the distance from the nearest river.

Risk Factors for Intensive Care Unit Admission and In-hospital Mortality Among Hospitalized Adults Identified through the US Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET).

BACKGROUND: Currently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk factors for severe outcomes among adults hospitalized with COVID-19. METHODS: We analyzed data from 2491 adults hospitalized with laboratory-confirmed COVID-19 between 1 March-2 May 2020, as identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, which comprises 154 acute-care hospitals in 74 counties in 13 states. We used multivariable analyses to assess associations between age, sex, race and ethnicity, and underlying conditions with intensive care unit (ICU) admission and in-hospital mortality. RESULTS: The data show that 92% of patients had ≥1 underlying condition; 32% required ICU admission; 19% required invasive mechanical ventilation; and 17% died. Independent factors associated with ICU admission included ages 50-64, 65-74, 75-84, and ≥85 years versus 18-39 years (adjusted risk ratios [aRRs], 1.53, 1.65, 1.84, and 1.43, respectively); male sex (aRR, 1.34); obesity (aRR, 1.31); immunosuppression (aRR, 1.29); and diabetes (aRR, 1.13). Independent factors associated with in-hospital mortality included ages 50-64, 65-74, 75-84, and ≥ 85 years versus 18-39 years (aRRs, 3.11, 5.77, 7.67, and 10.98, respectively); male sex (aRR, 1.30); immunosuppression (aRR, 1.39); renal disease (aRR, 1.33); chronic lung disease (aRR 1.31); cardiovascular disease (aRR, 1.28); neurologic disorders (aRR, 1.25); and diabetes (aRR, 1.19). CONCLUSIONS: In-hospital mortality increased markedly with increasing age. Aggressive implementation of prevention strategies, including social distancing and rigorous hand hygiene, may benefit the population as a whole, as well as those at highest risk for COVID-19-related complications.

Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study.

OBJECTIVE: To understand the epidemiology and burden of severe coronavirus disease 2019 (covid-19) during the first epidemic wave on the west coast of the United States. DESIGN: Prospective cohort study. SETTING: Kaiser Permanente integrated healthcare delivery systems serving populations in northern California, southern California, and Washington state. PARTICIPANTS: 1840 people with a first acute hospital admission for confirmed covid-19 by 22 April 2020, among 9 596 321 healthcare plan enrollees. Analyses of hospital length of stay and clinical outcomes included 1328 people admitted by 9 April 2020 (534 in northern California, 711 in southern California, and 83 in Washington). MAIN OUTCOME MEASURES: Cumulative incidence of first acute hospital admission for confirmed covid-19, and subsequent probabilities of admission to an intensive care unit (ICU) and mortality, as well as duration of hospital stay and ICU stay. The effective reproduction number (RE ) describing transmission dynamics was estimated for each region. RESULTS: As of 22 April 2020, cumulative incidences of a first acute hospital admission for covid-19 were 15.6 per 100 000 cohort members in northern California, 23.3 per 100 000 in southern California, and 14.7 per 100 000 in Washington. Accounting for censoring of incomplete hospital stays among those admitted by 9 April 2020, the estimated median duration of stay among survivors was 9.3 days (with 95% staying 0.8 to 32.9 days) and among non-survivors was 12.7 days (1.6 to 37.7 days). The censoring adjusted probability of ICU admission for male patients was 48.5% (95% confidence interval 41.8% to 56.3%) and for female patients was 32.0% (26.6% to 38.4%). For patients requiring critical care, the median duration of ICU stay was 10.6 days (with 95% staying 1.3 to 30.8 days). The censoring adjusted case fatality ratio was 23.5% (95% confidence interval 19.6% to 28.2%) among male inpatients and 14.9% (11.8% to 18.6%) among female inpatients; mortality risk increased with age for both male and female patients. Reductions in RE were identified over the study period within each region. CONCLUSIONS: Among residents of California and Washington state enrolled in Kaiser Permanente healthcare plans who were admitted to hospital with covid-19, the probabilities of ICU admission, of long hospital stay, and of mortality were identified to be high. Incidence rates of new hospital admissions have stabilized or declined in conjunction with implementation of social distancing interventions.

Emerging Challenges and Opportunities in Infectious Disease Epidemiology.

Much of the intellectual tradition of modern epidemiology stems from efforts to understand and combat chronic diseases persisting through the 20th century epidemiologic transition of countries such as the United States and United Kingdom. After decades of relative obscurity, infectious disease epidemiology has undergone an intellectual rebirth in recent years amid increasing recognition of the threat posed by both new and familiar pathogens. Here, we review the emerging coalescence of infectious disease epidemiology around a core set of study designs and statistical methods bearing little resemblance to the chronic disease epidemiology toolkit. We offer our outlook on challenges and opportunities facing the field, including the integration of novel molecular and digital information sources into disease surveillance, the assimilation of such data into models of pathogen spread, and the increasing contribution of models to public health practice. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. These areas represent an increasingly important component of epidemiology training programs for future generations of researchers and practitioners.

Antimicrobial resistance following mass azithromycin distribution for trachoma: a systematic review.

Mass azithromycin distribution is a core component of trachoma control programmes and could reduce mortality in children younger than 5 years in some settings. In this systematic review we synthesise evidence on the emergence of antimicrobial resistance after mass azithromycin distribution. We searched electronic databases for publications up to June 14, 2018. We included studies of any type (excluding modelling studies, surveillance reports, and review articles) on community-wide distribution of oral azithromycin for the prevention and treatment of trachoma that assessed macrolide resistance, without restrictions to the type of organism. We extracted prevalence of resistance from published reports and requested unpublished data from authors of included studies. Of 213 identified studies, 19 met inclusion criteria (12 assessed Streptococcus pneumoniae) and were used for qualitative synthesis. Macrolide resistance after azithromycin distribution was reported in three of the five organisms studied. The lack of resistance in Chlamydia trachomatis suggests that azithromycin might remain effective for trachoma programmes, but evidence is scarce. As mass azithromycin distribution for trachoma continues and is considered for other indications, ongoing monitoring of antimicrobial resistance will be required.

Risk of cardiovascular disease associated with exposure to abacavir among individuals with HIV: A systematic review and meta-analyses of results from 17 epidemiologic studies.

OBJECTIVES: Abacavir's potential to cause cardiovascular disease (CVD) among people living with HIV (PLWH) is debated. We conduct a systematic review and meta-analyses to assess CVD risk from recent and cumulative abacavir exposure. METHODS: We searched Medline, Embase, Web of Science, abstracts from Conference on Retroviruses and Opportunistic Infections, and International AIDS Society/AIDS Conferences and bibliographies of review articles to identify research studies published through 2018 on CVD risk associated with abacavir exposure among PLWH. Studies assessing risk of CVD associated with recent (exposure within last 6 months) or cumulative abacavir exposure across all age-groups were eligible. Risks were quantified using fixed- and random-effects models. RESULTS: Of 378 unique citations, 68 full-text research articles and abstracts were reviewed. Seventeen studies assessed risk of CVD from recent or cumulative abacavir exposure. Summary relative risk (sRR) is increased for recent exposure (n=16 studies, sRR=1.61; 95% confidence interval: 1.48-1.75), higher in antiretroviral-therapy-naive population (n=5, 1.91; 1.48-2.46) and all studies reported RR>1. The sRR for recent exposure was similarly increased for the outcome of acute myocardial infarction, and for studies that adjusted for substance abuse, smoking, prior CVD, traditional CVD risk factors, and CD4 cell-count/HIV viral load. The sRR was increased for cumulative abacavir exposure (per year) (n=4, 1.12; 1.05-1.20) but no increase was seen after adjusting for recent exposure (n=5, 1.00; 0.93-1.08). CONCLUSIONS: Our findings suggest an increased risk of CVD from recent abacavir exposure. The risk remained elevated after adjusting for potential confounders. Further investigations are needed to understand CVD risk from cumulative exposure.

Measles and Rubella Global Strategic Plan 2012-2020 midterm review report: Background and summary.

Measles, a vaccine-preventable illness, is one of the most infectious diseases known to man. In 2015, an estimated 134,200 measles deaths occurred globally. Rubella, also vaccine-preventable, is a concern because infection during pregnancy can result in congenital defects in the baby. More than 100,000 babies with congenital rubella syndrome were estimated to have been born globally in 2010. Eradication of both measles and rubella is considered to be feasible, beneficial, and more cost-effective than high-level control. All six World Health Organization (WHO) regions have measles elimination goals by 2020 and two have rubella elimination goals by that year. However, the World Health Assembly has not endorsed a global eradication goal for either disease. In 2012, the Measles and Rubella Initiative published a Global Measles and Rubella Strategic Plan, 2012-2020, referred to hereafter as the Plan, which aimed to achieve measles and rubella elimination in at least five WHO regions by end-2020 through the implementation of five core strategies, with progress evaluated against 2015 milestones. When, by end-2015, none of these milestones had been met, WHO's Strategic Advisory Group of Experts on Immunization (SAGE) recommended a mid-term review of the Plan to evaluate progress toward goals, assess the quality of strategy implementation, and formulate lessons learned. A five-member team reviewed documents and conducted interviews with stakeholders as the basis for the review's conclusions and recommendations. This team concluded that, although significant progress in measles elimination had been made, progress had slowed. It recommended that countries continue to work toward elimination goals with a focus on strengthening ongoing immunization systems. In addition, it concluded that the strategies articulated in the Plan were sound, however full implementation had been impeded by inadequate country ownership and global political will, reflected in inadequate resources. Detailed recommendations for each of the Plan's five strategies as well as the areas of polio transition, governance and resource mobilization are outlined.

Risk of cardiovascular events from current, recent, and cumulative exposure to abacavir among persons living with HIV who were receiving antiretroviral therapy in the United States: a cohort study.

BACKGROUND: There is ongoing controversy regarding abacavir use in the treatment of HIV infection and the risk of subsequent development of cardiovascular disease. It is unclear how the risk varies as exposure accumulates. METHODS: Using an administrative health-plan dataset, risk of cardiovascular disease events (CVDe), defined as the first episode of an acute myocardial infarction or a coronary intervention procedure, associated with abacavir exposure was assessed among HIV-infected individuals receiving antiretroviral therapy across the U.S. from October 2009 through December 2014. The data were longitudinal, and analyzed using marginal structural models. RESULTS: Over 114,470 person-years (n = 72,733) of ART exposure, 714 CVDe occurred at an incidence rate (IR) (95% CI) of 6·23 (5·80, 6·71)/1000 person-years. Individuals exposed to abacavir had a higher IR of CVDe of 9·74 (8·24, 11·52)/1000 person-years as compared to 5·75 (5·30, 6·24)/1000 person-years for those exposed to other antiretroviral agents. The hazard (HR; 95% CI) of CVDe was increased for current (1·43; 1·18, 1·73), recent (1·41; 1·16, 1·70), and cumulative [(1·18; 1·06, 1·31) per year] exposure to abacavir. The risk for cumulative exposure followed a bell-shaped dose-response curve peaking at 24-months of exposure. Risk was similarly elevated among participants free of pre-existing heart disease or history of illicit substance use at baseline. CONCLUSION: Current, recent, and cumulative use of abacavir was associated with an increased risk of CVDe. The findings were consistent irrespective of underlying cardiovascular risk factors.

Generalisability of vaccine effectiveness estimates: an analysis of cases included in a postlicensure evaluation of 13-valent pneumococcal conjugate vaccine in the USA.

OBJECTIVES: External validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA. DESIGN: Matched case-control study. SETTING: Thirteen active surveillance sites for invasive pneumococcal disease in the USA. PARTICIPANTS: Cases were identified from active surveillance and controls were age and zip code matched. OUTCOME MEASURES: Socioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment. RESULTS: We enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p<0.01). Enrolled cases also tended to come from more affluent census tracts. Despite these differences, our best predictive model for enrolment yielded a concordance statistic of only 0.703, indicating mediocre predictive value. Variables retained in the final model were assessed for effect measure modification, and none were found to be significant modifiers of vaccine effectiveness. CONCLUSIONS: We conclude that although enrolled cases are somewhat more affluent than unenrolled cases, our estimates are externally valid with respect to socioeconomic status. Our analysis provides evidence that this study design can yield valid estimates and the assessing generalisability of observational data is feasible, even when unenrolled individuals cannot be contacted.

Recommendations of the Advisory Committee on Immunization Practices for Use of Cholera Vaccine.

Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can be severe and rapidly fatal without prompt rehydration. Cholera is endemic in approximately 60 countries and causes epidemics as well. Globally, cholera results in an estimated 2.9 million cases of disease and 95,000 deaths annually (1). Cholera is rare in the United States, and most U.S. cases occur among travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases were reported in 2011 after a cholera epidemic began in Haiti (2); however, <25 cases per year have been reported in the United States since 2012.

Alcohol use among fatally injured victims in São Paulo, Brazil: bridging the gap between research and health services in developing countries.

BACKGROUND AND AIMS: Most studies reporting alcohol use among fatally injured victims are subject to bias, particularly those related to sample selection and to absence of injury context data. We developed a research method to estimate the prevalence of alcohol consumption and test correlates of alcohol use prior to fatal injuries. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study based on a probability sample of fatally injured adult victims (n = 365) autopsied in São Paulo, Brazil. Victims were sampled within systematically selected 8-hour sampling blocks, generating a representative sample of fatal injuries occurring during all hours of the day for each day of the week between June 2014 and December 2015. MEASUREMENTS: The presence of alcohol and blood alcohol concentration (BAC) were the primary outcomes evaluated according to victims' socio-demographic, injury context data (type, day, time and injury place) and criminal history characteristics. FINDINGS: Alcohol was detected in 30.1% [95% confidence interval (CI) = 25.6-35.1)] of the victims, with a mean blood alcohol level (BAC) level of 0.11% w/v (95% CI = 0.09-0.13) among alcohol-positive cases. Black and mixed race victims presented a higher mean BAC than white victims (P = 0.03). Fewer than one in every six suicides tested positive for alcohol, while almost half of traffic-related casualties were alcohol-positive. Having suffered traffic-related injuries, particularly those involving vehicle crashes, and injuries occurring during weekends and at night were associated significantly with alcohol use before injury (P < 0.05). CONCLUSIONS: Nearly one-third of fatal injuries in São Paulo between June 2014 and December 2015 were alcohol-related, with traffic accidents showing a greater association with alcohol use than other injuries. The sampling methodology tested here, including the possibility of adding injury context data to improve population-based estimates of alcohol use before fatal injury, appears to be a reliable and lower-cost strategy for avoiding biases common in death investigations.

Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

OBJECTIVES:  To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. DESIGN:  Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. STUDY ELIGIBILITY CRITERIA:  Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. DATA SOURCES:  Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. RESULTS:  Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. CONCLUSIONS:  Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.