Identifying and characterizing high-risk populations in pilot malaria elimination districts in Madagascar: a mixed-methods study.

BACKGROUND: In Madagascar, the districts of Antsirabe II, Faratsiho and Antsiranana I have relatively low malaria incidence rates and have been selected by the National Malaria Control Programme for pilot elimination strategies. The districts have residual transmission despite increasing coverage and quality of malaria services. This study sought to identify priority subpopulations at highest risk for malaria and collect information on intervention preferences and methods that will inform subnational tailoring of malaria service delivery. METHODS: This mixed methods study employed (i) a quantitative malaria risk factor assessment in Antsirabe II and Faratsiho comprising a test-negative frequency matched case-control study and a qualitative risk factor assessment in Antsiranana I; and (ii) a qualitative formative assessment in all three districts. For the case-control study, a mixed effects logistic regression was used with age, sex and district included as fixed effects and health facility included as a random effect. The qualitative risk factor assessment used semi-structured interview guides and key informant interviews. For the qualitative formative assessment in the three districts, a summary report was generated following semi-structured interviews and focus group discussions with high-risk populations (HRPs) and stakeholders. RESULTS: In Antsirabe II and Faratsiho districts, rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In Antsiranana I, respondents identified non-rice farmers, mobile vendors, and students as HRPs. Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive treatment and involvement of gatekeepers or people who have influence over intervention access or participation. CONCLUSIONS: The study results illustrate the value of in-depth assessments of risk behaviours, access to services and prevention tools, surveillance and prevention strategies, and the involvement of gatekeepers in shaping subnational tailoring to reach previously unreached populations and address residual transmission in elimination settings.

Demographic changes in COVID-19 mortality during the pandemic: analysis of trends in disparities among workers using California's mortality surveillance system.

BACKGROUND: There is limited information on the extent and patterns of disparities in COVID-19 mortality throughout the pandemic. We aimed to examine trends in disparities by demographics over variants in the pre- and post-vaccine availability period among Californian workers using a social determinants of health lens. METHODS: Using death certificates, we identified all COVID-19 deaths that occurred between January 2020 and May 2022 among workers aged 18-64 years in California (CA). We derived estimates for at-risk worker populations using the Current Population Survey. The waves of COVID-19 mortality in the pre-vaccine availability period were March 2020-June 2020 (wave 1), and July 2020-November 2020 (wave 2), and in the post-vaccine availability period: December 2020-May 2021 (wave 3), June 2021-January 2022 (wave 4), and February 2022-May 2022 (wave 5). Poisson regression models with robust standard errors were used to determine wave-specific mortality rate ratios (MRRs). We examined the change in MRR across waves by including an interaction term between each demographic characteristic and wave period in different models. The role of potential misclassification of Race/ethnicity on death certificates was examined using probabilistic quantitative bias analysis as sensitivity analysis. RESULTS: Among the 24.1 million working age CA population included in the study, there were 26,068 COVID-19 deaths in the period between January 2020 and May 2022. Compared with their respective reference groups, workers who were 50-64 years old, male, Native Hawaiian, Latino, or African American, foreign-born; individuals who had lower education; and unmarried were disproportionately affected by COVID-19 mortality. While disparities by sex, race/ethnicity and foreign-born status narrowed in later waves (post-vaccine availability), disparities by age, education level and marital status did not change substantially across waves. CONCLUSION: Demographic disparities in COVID-19 mortality narrowed in the post-vaccine availability waves. However, the existence of disparities across all waves of the pandemic, even in an era of widespread vaccine coverage, could indicate remaining gaps in prevention and differential vulnerability. Addressing the underlying social, structural, and occupational factors that contribute to these disparities is critical for achieving health equity.

COVID-19 Outbreaks and Mortality Among Public Transportation Workers - California, January 2020-May 2022.

Work-related factors can contribute to risk for exposure to and infection with SARS-CoV-2, the virus that causes COVID-19, and subsequent COVID-19-attributable outcomes, including death. Comparing COVID-19 metrics across industries can help identify workers at highest risk. Elevated COVID-19 mortality rates have been reported among all transportation workers, as well as specifically in public transportation industries (1-3). The California Department of Public Health (CDPH) calculated public transportation industry-specific COVID-19 outbreak incidence during January 2020-May 2022 and analyzed all laboratory-confirmed COVID-19 deaths among working-age adults in California to calculate public transportation industry-specific mortality rates during the same period. Overall, 340 confirmed COVID-19 outbreaks, 5,641 outbreak-associated cases, and 537 COVID-19-associated deaths were identified among California public transportation industries. Outbreak incidence was 5.2 times as high (129.1 outbreaks per 1,000 establishments) in the bus and urban transit industry and 3.6 times as high in the air transportation industry (87.7) as in all California industries combined (24.7). Mortality rates were 2.1 times as high (237.4 deaths per 100,000 workers) in transportation support services and 1.8 times as high (211.5) in the bus and urban transit industry as in all industries combined (114.4). Workers in public transportation industries are at higher risk for COVID-19 workplace outbreaks and mortality than the general worker population in California and should be prioritized for COVID-19 prevention strategies, including vaccination and enhanced workplace protection measures.

Neuropathic Pain in the Eyes, Body, and Mouth: Insights from the Sjögren's International Collaborative Clinical Alliance.

OBJECTIVE: To evaluate how ocular, oral, and bodily neuropathic pain symptoms, which characterize small fiber neuropathies, are associated with Sjögren's syndrome (SS) classification based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. METHODS: Participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry had ocular, rheumatologic, oral, and labial salivary gland (LSG) biopsy examinations, blood and saliva samples collected, and completed questionnaires at baseline. We used mixed effects modeling with age, country, gender, and depression being fixed effects and study site, a random effect, to determine if neuropathic pain indicators (assessed via questionnaires) were associated with being classified as SS. RESULTS: A total of 3,514 participants were enrolled into SICCA, with 1,541 (52.9%) meeting the 2016 ACR/EULAR classification criteria for SS. There was a negative association between being classified as SS and experiencing bodily neuropathic pain features of needle-like pain, prickling/tingling sensation, ocular neuropathic pain of constant burning, and constant light sensitivity, and having a presumptive diagnosis of neuropathic oral pain. CONCLUSIONS: We found that those classified as SS had lower scores/reports of painful neuropathies compared with those classified as non-SS. Non-SS patients with dry eye disease or symptoms could benefit from pain assessment as they may experience painful small-fiber neuropathies (SFNs). Pain questionnaires may help identify pain associated with SFNs in patients with SS and non-SS dry eye. Future studies would be helpful to correlate self-reports of pain to objective measures of SFNs in those with SS, non-SS dry eye, and healthy controls.

Central Corneal Subbasal Nerve Plexus Abnormalities in Sjögren Disease: A Pilot Study.

PURPOSE: Small-fiber neuropathy (SFN) is known to be associated with Sjögren disease (SjD), and in vivo corneal confocal microscopy can identify features compatible with SFN. Here, we performed a descriptive study to identify features of SFN of the corneal subbasal nerve plexus using in vivo confocal microscopy. METHODS: We recruited 10 participants from the Sjögren's International Collaborative Clinical Alliance (SICCA), 1 new participant (in an effort to expand the SICCA cohort), and 22 healthy controls. All participants underwent slit-lamp examination and in vivo confocal microscopy of the central corneal subbasal nerve plexus centered about the central whorl to create a 30-image montage. Each image was analyzed with automated software (ACCmetrics, Manchester, United Kingdom) to produce 7 nerve metrics. We performed t-tests and age-adjusted regressions to make comparisons of nerve metrics between participants with SjD and healthy controls. RESULTS: Most nerve metrics were significantly lower in participants with SjD compared with healthy controls. The mean corneal nerve fiber density was found to be 3.5 mm/mm 2 in participants with SjD compared with 10.6 mm/mm 2 in healthy controls (95% confidence interval, -8.4 to -0.93; P = 0.02). Within the 11 participants with SjD, 22 eyes were analyzed on confocal microscopy, and 16 of those eyes (from 9 individuals) did not have an identifiable central whorl. Within the 22 healthy controls, 22 eyes (right eye alone) were analyzed on confocal microscopy, and 21 of those eyes had an identifiable central whorl. CONCLUSIONS: SjD exhibits lower corneal nerve metrics compared with healthy controls. These findings suggest that features compatible with SFN can distinguish SjD from healthy controls and may serve as a potential novel biomarker in identifying SjD.

Occupational COVID-19 Exposures and Illnesses among Workers in California-Analysis of a New Occupational COVID-19 Surveillance System.

Little is known about occupational SARS-CoV-2 exposures and COVID-19 outcomes. We established a Doctor's First Reports of Occupational Injury or Illness (DFR)-based surveillance system to study cases of work-related COVID-19 exposures and disease. The surveillance data included demographics, occupation, industry, exposure, and illness, details including hospitalization and lost work. We classified workers into 'healthcare', non-healthcare 'public-facing', or 'other' worker groups, and rural-urban commuting areas (RUCAs). We describe worker exposures and outcomes overall by worker group and RUCA. We analyzed 2848 COVID-19 DFRs representing workers in 22 detailed occupation groups and 19 industry groups. Most DFRs were for workers in metropolitan RUCAs (89%) and those in healthcare (42%) and public-facing (24%) worker groups. While DFRs were from 382 unique worksites, 52% were from four hospitals and one prison. Among 1063 DFRs with a suspected exposure, 73% suspected exposure to a patient or client. Few DFRs indicated hospitalization (3.9%); however, the proportion hospitalized was higher among nonmetropolitan (7.4%) and public-facing (6.7%) workers. While 56% of DFRs indicated some lost work time, the proportion was highest among public-facing (80%) workers. Healthcare and prison workers were the majority of reported occupational COVID-19 exposures and illnesses. The risk of COVID-19 hospitalization and lost work may be highest among nonmetropolitan and public-facing workers.

Influence of maternal age on birth and infant outcomes at 6 months: a cohort study with quantitative bias analysis.

BACKGROUND: Maternal age is increasingly recognized as a predictor of birth outcomes. Given the importance of birth and growth outcomes for children's development, wellbeing and survival, this study examined the effect of maternal age on infant birth and growth outcomes at 6 months and mortality. Additionally, we conducted quantitative bias analysis (QBA) to estimate the role of selection bias and unmeasured confounding on the effect of maternal age on infant mortality. METHODS: We used data from randomized-controlled trials (RCTs) of 21 555 neonates in Burkina Faso conducted in 2019-2020. Newborns of mothers aged 13-19 years (adolescents) and 20-40 years (adults) were enrolled in the study 8-27 days after birth and followed for 6 months. Measurements of child's anthropometric measures were collected at baseline and 6 months. We used multivariable linear regression to compare child anthropometric measures at birth and 6 months, and logistic regression models to obtain the odds ratio (OR) of all-cause mortality. Using multidimensional deterministic analysis, we assessed scenarios in which the difference in selection probability of adolescent and adult mothers with infant mortality at 6 months increased from 0% to 5%, 10%, 15% and 20% if babies born to adolescent mothers more often died during the first week or were of lower weight and hence were not eligible to be included in the original RCT. Using probabilistic bias analysis, we assessed the role of unmeasured confounding by socio-economic status (SES). RESULTS: Babies born to adolescent mothers on average had lower weight at birth, lower anthropometric measures at baseline, similar growth outcomes from enrolment to 6 months and higher odds of all-cause mortality by 6 months (adjusted OR = 2.17, 95% CI 1.35 to 3.47) compared with those born to adult mothers. In QBA, we found that differential selection of adolescent and adult mothers could bias the observed effect (OR = 2.24, 95% CI 1.41 to 3.57) towards the null [bias-corrected OR range: 2.37 (95% CI 1.49 to 3.77) to 2.84 (95% CI 1.79 to 4.52)], whereas unmeasured confounding by SES could bias the observed effect away from the null (bias-corrected OR: 2.06, 95% CI 1.31 to 2.64). CONCLUSIONS: Our findings suggest that delaying the first birth from adolescence to adulthood may improve birth outcomes and reduce mortality of neonates. Babies born to younger mothers, who are smaller at birth, may experience catch-up growth, reducing some of the anthropometric disparities by 6 months of age.

The Association between Malnutrition and Malaria Infection in Children under 5 Years in Burkina Faso: A Longitudinal Study.

The relationship between malaria infection and malnutrition is complex. Using data from a randomized controlled trial of 450 children 0-5 years of age in Burkina Faso, we examined the effect of malaria infection on short-term changes in anthropometric measures, the effect of malnutrition on malaria infection, and whether age modified the effect of baseline anthropometric measures on malaria infection. Malaria infection, assessed by blood smear microscopy and weight, height, mid-upper arm circumference, height-for-age z-score, weight-for-age z-score, and weight-for-height z-score were measured at three time points: baseline, 2 weeks, and 6 months. We used generalized estimating equations adjusted for sex, age, breastfeeding, maternal education, and study treatment (azithromycin versus placebo) for all analyses. Interaction terms were used to assess effect modification by age. Among the 366 children with no malaria infection at baseline, 43 (11.6%) had malaria infection within 6 months. There were no important differences in anthropometric measures at 2 weeks and 6 months between those with and without malaria infection at baseline. There were no significant differences in prevalence of malaria infection by baseline anthropometric measures. Age (0-30 months versus 30-60 months) modified the effect of baseline weight and height on malaria infection. Among those aged 0-30 months, for each kilogram increase in weight, malaria infection increased by 27% (95% CI: 6-53%), and for each centimeter increase in height, it increased by 9% (95% CI: 1-17%), but there were no differences for those aged 30-60 months.

Temporal assessment of disparities in California COVID-19 mortality by industry: a population-based retrospective cohort study.

PURPOSE: To assess changes in the COVID-19 mortality rate and disparities over variants or waves by industry. METHODS: We identified COVID-19 deaths that occurred between January 2020 and May 2022 among California workers aged 18-64 years using death certificates, and estimated Californians at risk using the Current Population Survey. The waves in deaths were wave 1: March-June 2020, wave 2: July-November 2020, wave 3/Epsilon and Alpha variants: December 2020-May 2021, wave 4/Delta variant: June 2021-January 2022, and wave 5/Omicron variant: February-May 2022. We used Poisson regression to generate wave-specific mortality rate ratios (MRR) and included an interaction term between industry and wave in different models to assess significance of the change in MRR. RESULTS: In all waves of the pandemic, healthcare, other services, manufacturing, transportation, and retail trade industries had higher mortality rates than the professional, scientific, and technical industry. The healthcare industry had the highest relative rate earlier in the pandemic, while other services, utilities, and accommodation and food services industries had substantial increases in MRR in later waves. CONCLUSIONS: Industries that consistently had disproportionate COVID-19 mortality may have benefitted from protections that consider workers' increased exposure and vulnerability to severe outcomes.

Associations Between Smoking and Primary Sjögren Syndrome Classification Using the Sjögren's International Collaborative Clinical Alliance Cohort.

OBJECTIVE: The objective of this study was to examine the association of smoking with Primary Sjögren syndrome (pSS) classification and pSS diagnostic test results. We hypothesized that past and current smokers would have lower odds of being classified as having Sjögren syndrome (SS) and lower odds of having abnormal individual SS diagnostic test results compared with nonsmokers. METHODS: Participants with suspected or established pSS were enrolled into the Sjögren's International Collaborative Clinical Alliance (SICCA) registry and had oral, ocular, and rheumatologic examinations performed; blood and saliva samples collected; and labial salivary gland biopsy examinations performed; they also completed questionnaires at baseline. Logistic regression was used to determine whether smoking status was associated with pSS classification and individual pSS diagnostic test results. RESULTS: A total of 3514 participants were enrolled in SICCA. A total of 1541 (52.9%) met classification criteria for pSS. Compared with never smokers, current smokers had reduced odds of being classified as having pSS, reduced odds of having a focus score ≥ 1 and serologic positivity for anti-SSA/anti-SSB antibodies, and lower odds of having abnormal signs or test results of dry eye disease. Compared with never smokers, past smokers did not have a statistically significant reduction in odds of being classified as having pSS and of having abnormal individual pSS diagnostic test results. CONCLUSION: Compared with never smokers, current smokers in the SICCA cohort had lower odds of being classified as having pSS, lower odds of exhibiting abnormal signs and test results for dry eye disease, and lower odds of having a labial salivary gland biopsy supportive of pSS classification. Such negative associations, however, do not suggest that current smoking is of any benefit with respect to pSS.

The Role of Neighborhood Poverty in the Association between Foreign-Born status and HIV Care Continuum Outcomes in Alameda County, California.

Foreign-born persons living in the US have an increased risk of exposure to HIV and higher rates of HIV diagnosis (Patel-Larson et al. in Poster presented at the 2007 National HIV Prevention Conference, pp 2-5, 2007; Prosser et al. in JAMA 308:601-607, 2012). Foreign-born persons also tend to live in areas with high concentration of immigrants and more often neighborhoods of high poverty, for at least some time (Jargowsky in J Ethn Migr Stud 35:1129-1151, 2009). Using HIV surveillance data in Alameda County, California, we examined whether the association between immigrant status and the four outcomes on the HIV care cascade (late diagnosis, linkage to care within 30 days of diagnosis, retention in HIV care, and viral load status a year after diagnosis) differed by census tract poverty level. We used generalized estimating equations (GEE) adjusted for sex at birth, age, race, and transmission mode. Of 1235 individuals with HIV diagnosis reported between 2011 and 2016, 29% were foreign-born. Foreign-born status was significantly associated with late HIV diagnosis but not with linkage, retention in care, and achievement of undetectable viral load a year after diagnosis. Neighborhood poverty modified the association between immigrant status and retention in care, but not late diagnosis, linkage or viral load status. Our findings suggest that neighborhood resources may buffer against disparities in retention. Thus, immigrants in poorer neighborhoods may require more support to stay in care.

A double masked randomised 4-week, placebo-controlled study in the USA, Thailand and Taiwan to compare the efficacy of oral valganciclovir and topical 2% ganciclovir in the treatment of cytomegalovirus anterior uveitis: study protocol.

INTRODUCTION: Cytomegalovirus (CMV) anterior uveitis is a recognised cause of anterior uveitis in immunocompetent patients and is preventable cause of vision loss. Ocular sequelae include corneal endothelial damage which can cause corneal oedema and failure, as well as glaucoma. Recurrences of inflammation are common and therefore patients are often exposed to long-term therapy. Oral therapy is available in the form of valganciclovir, although with the caveat of systemic side effects such as bone marrow suppression and renal failure necessitating regular interval laboratory monitoring. Recent reports have demonstrated that topical 2% ganciclovir solution may offer promising treatment outcomes in patients with CMV anterior uveitis with superior safety, cost-effectiveness and convenience profiles. An investigation into the relative equipoise of these therapies is warranted for these reasons. METHODS AND ANALYSIS: The Systemic and Topical Control of Cytomegalovirus Anterior uveitis: Treatment Outcomes (STACCATO) trial is designed as a multicentre, block randomised by site, double-masked, placebo-controlled trial comparing the efficacy of oral valganciclovir, 2% topical ganciclovir and placebo in treating PCR-proven CMV anterior uveitis. Participant clinical evaluation will occur at three study time points by a masked study ophthalmologist over a 28-day period to assess resolution of ocular inflammation (secondary outcome). A control group will provide additional information about the possible impact that the infected host's immune response may play in controlling local viral replication. The primary analysis is an analysis of covariance (three arms) correcting for baseline to compare quantitative CMV viral load in the anterior chamber (AC) aqueous fluid before and 7 days after treatment. ETHICS AND DISSEMINATION: The University of California San Francisco Committee on Human Research and the Khon Kaen University Institutional Review Board have given ethical approval. The results of this trial will be presented at local and international meetings and submitted for peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: NCT03576898.