Characterizing the etiology of recurrent tuberculosis using whole genome sequencing-Alaska, USA, 2008-2020.

BACKGROUND: Understanding the etiology of recurrent tuberculosis (rTB) is important for effective TB control. Prior to the advent of whole genome sequencing (WGS), attributing rTB to relapse or reinfection using genetic information was complicated by the limited resolution of conventional genotyping methods. METHODS: We applied a systematic method of evaluating whole genome single nucleotide polymorphism (wgSNP) distances and results of phylogenetic analyses to characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska during 2008-2020. We contextualized our findings through descriptive analyses of surveillance data and results of a literature search for investigations that characterized rTB etiology using WGS. RESULTS: The percentage of TB cases in AIAN persons in Alaska classified as recurrent episodes (11.8%) was three times the national percentage (3.9%). Of 38 recurrent episodes included in genetic analyses, we attributed 25 (65.8%) to reinfection based on wgSNP distances and phylogenetic analyses; this proportion was the highest among 16 published point estimates identified through the literature search. By comparison, we attributed 11 of 38 (28.9%) and 6 of 38 (15.8%) recurrent episodes to reinfection based on wgSNP distances alone and on conventional genotyping methods, respectively. CONCLUSIONS: WGS and attribution criteria involving genetic distances and patterns of relatedness can provide an effective means of elucidating rTB etiology. Our findings indicate that rTB occurs at high proportions among AIAN persons in Alaska and is frequently attributable to reinfection, reinforcing the importance of active surveillance and control measures to limit the spread of TB disease in Alaskan AIAN communities.

Using Geographic Disaggregation to Compare Tuberculosis Epidemiology Among American Indian and Alaska Native Persons-USA, 2010-2020.

BACKGROUND: American Indian and Alaska Native (AIAN) populations are frequently associated with the highest rates of tuberculosis (TB) disease of any racial/ethnic group in the USA. We systematically investigated variation in patterns and potential drivers of TB epidemiology among geographically distinct AIAN subgroups. METHODS: Using data reported to the National Tuberculosis Surveillance System during 2010-2020, we applied a geographic method of data disaggregation to compare annual TB incidence and the frequency of TB patient characteristics among AIAN persons in Alaska with AIAN persons in other states. We used US Census data to compare the prevalence of substandard housing conditions in AIAN communities in these two geographic areas. RESULTS: The average annual age-adjusted TB incidence among AIAN persons in Alaska was 21 times higher than among AIAN persons in other states. Compared to AIAN TB patients in other states, AIAN TB patients in Alaska were associated with significantly higher frequencies of multiple epidemiologic TB risk factors (e.g., attribution of TB disease to recent transmission, previous diagnosis of TB disease) and significantly lower frequencies of multiple clinical risk factors for TB disease (e.g., diagnosis with diabetes mellitus, end-stage renal disease). Occupied housing units in AIAN communities in Alaska were associated with significantly higher frequencies of multiple measures of substandard housing conditions compared to AIAN communities in other states. CONCLUSIONS: Observed differences in patient characteristics and substandard housing conditions are consistent with contrasting syndromes of TB epidemiology in geographically distinct AIAN subgroups and suggest ways that associated public health interventions could be tailored to improve efficacy.

Effects of Rurality on Distance and Time Traveled to Receive Vaccination Against Mpox-New Mexico and Idaho 2022-2023.

ABSTRACT: We compared mpox vaccination access between urban and rural residents who received ≥1 JYNNEOS dose using immunization data in Idaho and New Mexico. Rural residents traveled 5 times farther and 3 times longer than urban residents to receive mpox vaccination. Increasing mpox vaccine availability to health care facilities might increase uptake.

Multipathogen Outbreak of Bacillus cereus and Clostridium perfringens Among Hospital Workers in Alaska, August 2021.

OBJECTIVE: Clostridium perfringens and Bacillus cereus are common causes of reported foodborne illness. On August 6, 2021, the Alaska Division of Public Health identified a multipathogen gastrointestinal outbreak among hospital staff in Homer, Alaska. The objectives of this study were to identify the outbreak source and prevent future illness. METHODS: We conducted a retrospective cohort study of hospital staff who participated in luncheon events during August 5-7, 2021, and used an online survey to identify hospital staff with gastrointestinal illness. We defined case patients as people who reported new-onset gastrointestinal illness (diarrhea or abdominal cramping) after food consumption during the luncheon events. We calculated adjusted odds ratios of gastrointestinal illness associated with reported food exposures. We tested available food samples for C perfringens and B cereus and tested case patient stool specimens for C perfringens. We conducted an environmental investigation at the implicated vendor site. RESULTS: Of 202 survey responses, 66 (32.7%) people reported acute gastrointestinal illness: 64 (97.0%) reported diarrhea, 62 (94.9%) reported abdominal cramps, and none were hospitalized. Of 79 people who consumed ham and pulled pork sandwiches, 64 (81.0%) met the case definition; this food item was significantly associated with increased odds of gastrointestinal illness (adjusted odds ratio = 296.4; 95% CI, 76.7-2019.1). C perfringens and B cereus were isolated at confirmatory levels from sandwich samples. C perfringens enterotoxin was detected in all 5 stool specimens tested. Environmental investigators observed other food items at the sandwich vendor that were refrigerated outside the required temperature range (>41 °F); no clear handling deficiencies for the implicated food were identified. CONCLUSION: Quick notification and effective collaboration can help detect an outbreak, identify the responsible food vehicle, and mitigate further risk.

Temporally Associated Invasive Pneumococcal Disease and SARS-CoV-2 Infection, Alaska, USA, 2020-2021.

Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated with SARS-CoV-2 infections is limited. We described the epidemiology and clinical course of patients who had invasive pneumococcal disease (IPD) and temporally associated SARS-CoV-2 infections in Alaska, USA, during January 1, 2020-December 23, 2021. Of 271 patients who had laboratory-confirmed IPD, 55 (20%) had a positive SARS-CoV-2 test result. We observed no major differences in age, race, sex, or underlying medical conditions among IPD patients with and without SARS-CoV-2. However, a larger proportion of IPD patients with SARS-CoV-2 died (16%, n = 9) than for those with IPD alone (4%, n = 9) (p<0.01). IPD patients with SARS-CoV-2 were also more likely to be experiencing homelessness (adjusted OR 3.5; 95% CI 1.7-7.5). Our study highlights the risk for dual infection and ongoing benefits of pneumococcal and COVID-19 vaccination, especially among vulnerable populations.

Long-term ambient air pollution exposure and cardio-respiratory disease in China: findings from a prospective cohort study.

BACKGROUND: Existing evidence on long-term ambient air pollution (AAP) exposure and risk of cardio-respiratory diseases in China is mainly on mortality, and based on area average concentrations from fixed-site monitors for individual exposures. Substantial uncertainty persists, therefore, about the shape and strength of the relationship when assessed using more personalised individual exposure data. We aimed to examine the relationships between AAP exposure and risk of cardio-respiratory diseases using predicted local levels of AAP. METHODS: A prospective study included 50,407 participants aged 30-79 years from Suzhou, China, with concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), fine (PM2.5), and inhalable (PM10) particulate matter, ozone (O3) and carbon monoxide (CO) and incident cases of cardiovascular disease (CVD) (n = 2,563) and respiratory disease (n = 1,764) recorded during 2013-2015. Cox regression models with time-dependent covariates were used to estimate adjusted hazard ratios (HRs) for diseases associated with local-level concentrations of AAP exposure, estimated using Bayesian spatio-temporal modelling. RESULTS: The study period of 2013-2015 included a total of 135,199 person-years of follow-up for CVD. There was a positive association of AAP, particularly SO2 and O3, with risk of major cardiovascular and respiratory diseases. Each 10 µg/m3 increase in SO2 was associated with adjusted hazard ratios (HRs) of 1.07 (95% CI: 1.02, 1.12) for CVD, 1.25 (1.08, 1.44) for COPD and 1.12 (1.02, 1.23) for pneumonia. Similarly, each 10 µg/m3 increase in O3 was associated with adjusted HR of 1.02 (1.01, 1.03) for CVD, 1.03 (1.02, 1.05) for all stroke, and 1.04 (1.02, 1.06) for pneumonia. CONCLUSIONS: Among adults in urban China, long-term exposure to ambient air pollution is associated with a higher risk of cardio-respiratory disease.

Long-Term Exposure to Ambient Fine Particulate Matter and Incidence of Major Cardiovascular Diseases: A Prospective Study of 0.5 Million Adults in China.

Few cohort studies explored the long-term effects of ambient fine particulate matter (PM2.5) on incidence of cardiovascular diseases (CVDs), especially in countries with higher levels of air pollution. We aimed to evaluate the association between long-term exposure to PM2.5 and incidence of CVD in China. We performed a prospective cohort study in ten regions that recruited 512,689 adults during 2004-2008, with follow-up until 2017. Annual PM2.5 concentrations were estimated using a satellite-based model with national coverage and 1 x 1 km spatial resolution. Time-varying Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for all-cause and cause-specific CVDs associated with PM2.5, adjusting for conventional covariates. During 5.08 million person-years of follow-up, 148,030 incident cases of CVD were identified. Long-term exposure to PM2.5 showed positive and linear association with incidence of CVD, without a threshold below any concentration. The adjusted HRs per 10 µg/m3 increase in PM2.5 was 1.04 (95%CI: 1.02, 1.07) for total CVD. The risk estimates differed between certain population subgroups, with greater HRs in men, in household with higher income, and in people using unclean heating fuels. This prospective study of large Chinese population provided essential epidemiological evidence for CVD incident risk associated with PM2.5.

Increased Mortality Among Persons With Symptomatic Coronavirus Disease 2019 (COVID-19) During the Period of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta Variant) Predominance: Alaska, November 2020-October 2021.

We compared the mortality risk in Alaska among persons with symptomatic coronavirus disease 2019 (COVID-19) during the period the Delta variant was predominant to the risk among those with symptomatic COVID-19 before Delta predominance. The Delta period was associated with 2.43-fold higher odds of death. Unvaccinated persons were 4.49 times more likely to die than fully vaccinated persons.

Estimating ambient air pollutant levels in Suzhou through the SPDE approach with R-INLA.

Spatio-temporal models of ambient air pollution can be used to predict pollutant levels across a geographical region. These predictions may then be used as estimates of exposure for individuals in analyses of the health effects of air pollution. Integrated nested Laplace approximations is a method for Bayesian inference, and a fast alternative to Markov chain Monte Carlo methods. It also facilitates the SPDE approach to spatial modelling, which has been used for modelling of air pollutant levels, and is available in the R-INLA package for the R statistics software. Covariates such as meteorological variables may be useful predictors in such models, but covariate misalignment must be dealt with. This paper describes a flexible method used to estimate pollutant levels for six pollutants in Suzhou, a city in China with dispersed air pollutant monitors and weather stations. A two-stage approach is used to address misalignment of weather covariate data.

Evaluating clinical characteristics studies produced early in the Covid-19 pandemic: A systematic review.

OBJECTIVES: Clinical characterisation studies have been essential in helping inform research, diagnosis and clinical management efforts, particularly early in a pandemic. This systematic review summarises the early literature on clinical characteristics of patients admitted to hospital, and evaluates the quality of evidence produced during the initial stages of the pandemic. METHODS: MEDLINE, EMBASE and Global Health databases were searched for studies published from January 1st 2020 to April 28th 2020. Studies which reported on at least 100 hospitalised patients with Covid-19 of any age were included. Data on clinical characteristics were independently extracted by two review authors. Study design specific critical appraisal tools were used to evaluate included studies: the Newcastle Ottawa scale for cohort and cross sectional studies, Joanna Briggs Institute checklist for case series and the Cochrane collaboration tool for assessing risk of bias in randomised trials. RESULTS: The search yielded 78 studies presenting data on 77,443 people. Most studies (82%) were conducted in China. No studies included patients from low- and middle-income countries. The overall quality of included studies was low to moderate, and the majority of studies did not include a control group. Fever and cough were the most commonly reported symptoms early in the pandemic. Laboratory and imaging findings were diverse with lymphocytopenia and ground glass opacities the most common findings respectively. Clinical data in children and vulnerable populations were limited. CONCLUSIONS: The early Covid-19 literature had moderate to high risk of bias and presented several methodological issues. Early clinical characterisation studies should aim to include different at-risk populations, including patients in non-hospital settings. Pandemic preparedness requires collection tools to ensure observational studies are methodologically robust and will help produce high-quality data early on in the pandemic to guide clinical practice and public health policy. REVIEW REGISTRATION: Available at https://osf.io/mpafn.

COVID-19 testing acceptability and uptake amongst the Rohingya and host community in Camp 21, Teknaf, Bangladesh.

Facility-based sentinel testing for COVID-19 was implemented in May 2020 to monitor the prevalence of COVID-19 amongst the Rohingya and host community in Cox's Bazar, Bangladesh. In response both to low uptake of testing across all camps, and rumours of an outbreak of an influenza-like illness in May/June 2020, the International Organization for Migration (in partnership with ACAPS) undertook a qualitative study to collect accounts from the Rohingya relating to testing and treatment, and to explore the possibility that what was thought to be an outbreak of influenza may have been COVID-19. The report provided rich descriptions of the apprehension around testing and offered some clear recommendations for addressing these. We developed a testing 'script' in response to these recommendations, deploying it alongside a survey to determine reasons for declining a test. We compared testing uptake before deploying the testing script, and after (controlling for the total number of consultations), to generate a crude measure of the impact of the script on testing uptake. We coded reasons for declining a test thematically, disaggregated by status (Rohingya and host community) and sex. Despite the small sample size our results suggest an increase in testing uptake following the implementation of the script. Reasons provided by patients for declining a test included: 1) fear, 2) the belief that COVID-19 does not exist, that Allah will prevent them from contracting it, or that their symptoms are not caused by COVID-19, 3) no permission from husband/family, and 4) a preference to return at a later time for a test. Our findings largely mirror the qualitative accounts in the International Organization for Migration/ACAPS report and suggest that further testing amongst both populations will be complicated by fear, and a lack of clarity around testing. Our data lend force to the recommendations in the International Organization for Migration/ACAPS report and emphasise that contextual factors play a key role and must be considered in designing and implementing a health response to a novel disease.

Aircraft noise and self-assessed mental health around a regional urban airport: a population based record linkage study.

BACKGROUND: Limited evidence suggests that residential exposure to aircraft noise negatively influences population mental health around large airports, but it is not known whether the same is true for smaller airports. We investigated whether residential exposure to aircraft noise near a regional urban airport was associated with risk of chronic self-assessed mental ill health. METHODS: This is a cross-sectional study of 198,532 people aged 18 years and over living in Belfast, United Kingdom, enumerated at the 2011 Census. Residential exposure to aircraft noise (LAeq,16h) was assessed by linking Census records with modelled noise contours surrounding George Best Belfast City Airport (c.42,000 annual aircraft movements). Associations between noise and mental ill health were estimated using multiple logistic regression adjusting for demographic characteristics, socio-economic status and comorbidity. RESULTS: Prevalence of self-assessed mental ill health was greater in high noise (≥57 dB) compared to low noise (< 54 dB) areas (12.4% vs. 9.7%). We found no association between aircraft noise and risk of mental ill health after adjustment for socio-economic status (high vs. low noise odds ratio: 1.03 CI: 0.93, 1.14). DISCUSSION: Associations between aircraft noise and mental health have been reported near large airports at similar average noise levels to those observed here. Our findings indicate that the noise environment around this smaller airport (with fewer flights and no night flights) has little influence on population mental health.

Cardiorespiratory health effects of gaseous ambient air pollution exposure in low and middle income countries: a systematic review and meta-analysis.

BACKGROUND: Lack of research on the effects of gaseous pollutants (nitrogen oxides [NOx], sulfur dioxide [SO2], carbon monoxide [CO] and ozone [O3]) in the ambient environment on health outcomes from within low and middle income countries (LMICs) is leading to reliance on results from studies performed within high income countries (HICs). This systematic review and meta-analysis examines the cardiorespiratory health effects of gaseous pollutants in LMICs exclusively. METHODS: Systematic searching was carried out and estimates pooled by pollutant, lag and outcome, and presented as excess relative risk per 10 µg/m3 (NOx, SO2, O3) or 1 ppm (CO) increase pollutant. Sub-group analysis was performed examining estimates by specific outcomes, city and co-pollutant adjustment. RESULTS: Sixty studies met the inclusion criteria, most (44) from the East Asia and Pacific region. A 10 µg/m3 increase in same day NOx was associated with 0.92% (95% CI: 0.44, 1.39), and 0.70% (0.01, 1.40) increases in cardiovascular and respiratory mortality respectively, same day NOx was not associated with morbidity. Same day sulfur dioxide was associated with 0.73% (0.04, 1.42) and 0.50% (0.01, 1.00) increases in respiratory morbidity and in cardiovascular mortality respectively. CONCLUSIONS: Acute exposure to gaseous ambient air pollution (AAP) is associated with increases in morbidity and mortality in LMICs, with greatest associations observed for cardiorespiratory mortality.

Cardiorespiratory health effects of particulate ambient air pollution exposure in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Most prospective studies on the health effects of particulate ambient air pollution exposure have focused on high-income countries, which have much lower pollutant concentrations than low-income and middle-income countries (LMICs) and different sources of pollution. We aimed to investigate the cardiorespiratory health effects of particulate ambient air pollution exposure in LMICs exclusively. METHODS: For this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, LILACS, Global Health, and Proquest for studies published between database inception and Nov 28, 2016, investigating the cardiorespiratory health effects of particulate ambient air pollution exposure in LMICs. Data were extracted from published studies by one author, and then checked and verified by all authors independently. We pooled estimates by pollutant type (particulate matter with a diameter of <2·5 µm [PM2·5] or 2·5-10 µm [PM10]), lag, and outcome, and presented them as excess relative risk per 10 µg/m3 increase in particulate ambient air pollution. We used a random-effects model to derive overall excess risk. The study protocol is registered with PROSPERO, number CRD42016051733. FINDINGS: Of 1553 studies identified, 91 met the full eligibility criteria. Only four long-term exposure studies from China were identified and not included in the meta-analysis. A 10 µg/m3 increase in same-day PM2·5 was associated with a 0·47% (95% CI 0·34-0·61) increase in cardiovascular mortality and a 0·57% (0·28-0·86) increase in respiratory mortality. A 10 µg/m3 increase in same-day PM10 was associated with a 0·27% (0·11-0·44) increase in cardiovascular mortality and a 0·56% (0·24-0·87) increase in respiratory mortality. INTERPRETATION: Short-term exposure to particulate ambient air pollution is associated with increases in cardiorespiratory morbidity and mortality in LMIC's, with apparent regional-specific variations. FUNDING: None.

Neural Point-and-Click Communication by a Person With Incomplete Locked-In Syndrome.

A goal of brain-computer interface research is to develop fast and reliable means of communication for individuals with paralysis and anarthria. We evaluated the ability of an individual with incomplete locked-in syndrome enrolled in the BrainGate Neural Interface System pilot clinical trial to communicate using neural point-and-click control. A general-purpose interface was developed to provide control of a computer cursor in tandem with one of two on-screen virtual keyboards. The novel BrainGate Radial Keyboard was compared to a standard QWERTY keyboard in a balanced copy-spelling task. The Radial Keyboard yielded a significant improvement in typing accuracy and speed-enabling typing rates over 10 correct characters per minute. The participant used this interface to communicate face-to-face with research staff by using text-to-speech conversion, and remotely using an internet chat application. This study demonstrates the first use of an intracortical brain-computer interface for neural point-and-click communication by an individual with incomplete locked-in syndrome.

Chronic fetal hypoxia produces selective brain injury associated with altered nitric oxide synthases.

OBJECTIVE: The purpose of this study was to investigate the impact of chronic hypoxia on the nitric oxide synthase isoenzymes in specific brain structures. STUDY DESIGN: Time-mated pregnant guinea pigs were exposed to 10.5% molecular oxygen for 14 days (animals with chronic fetal hypoxia; HPX) or room air (control animals; NMX); L-N6-(1-iminoethyl)-lysine (L-NIL; an inducible nitric oxide synthase inhibitor, 1 mg/kg/d) was administered to HPX group for 14 days (L-NIL + HPX). Fetal brains were harvested at term. Multilabeled immunofluorescence was used to generate a brain injury map. Laser capture microdissection and quantitative polymerase chain reaction were applied; cell injury markers, apoptosis activation, neuron loss, total nitric oxide, and the levels of individual nitric oxide synthase isoenzymes were quantified. RESULTS: Chronic hypoxia causes selective fetal brain injury rather than global. Injury is associated with differentially affected nitric oxide synthases in both neurons and glial cells, with inducible macrophage-type nitric oxide synthase up-regulated at all injury sites. L-NIL attenuated the injury, despite continued hypoxia. CONCLUSION: These studies demonstrate that chronic hypoxia selectively injures the fetal brain in part by the differential regulation of nitric oxide synthase isoenzymes in an anatomic- and cell-specific manner.