Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428-e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, "rhinocerebral mucormycosis." A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.

Pregnancy is associated with increased risk for severe illness and complications associated with influenza infection. Insufficient knowledge about the risk for influenza among pregnant women and their health care providers in China is an important barrier to increasing influenza vaccination coverage and treating influenza and its complications among pregnant women. Improved influenza incidence estimates might promote wider vaccine acceptance and higher vaccination coverage. In Suzhou, active population-based surveillance during October 2018-September 2023 estimated that the annual rate of hospitalization for acute respiratory or febrile illness (ARFI) among women who were pregnant or <2 weeks postpartum was 11.1 per 1,000 live births; the annual rate of laboratory-confirmed influenza-associated ARFI (influenza ARFI) hospitalization in this group was 2.1 per 1,000 live births. A majority of hospitalized pregnant or early postpartum patients with ARFI (82.6%; 2,588 of 3,133) or influenza ARFI (85.5%; 423 of 495) were admitted to obstetrics wards rather than respiratory medicine wards. Only one (0.03%) pregnant or postpartum ARFI patient had received influenza vaccination, and 31.3% of pregnant or postpartum women hospitalized for influenza ARFI received antiviral treatment; the lowest percentage of hospitalized women with influenza ARFI who received antiviral treatment was among women admitted to obstetrics and gynecology wards (29.6% and 23.1%, respectively), compared with 54.1% of those admitted to a respiratory medicine ward. These findings highlight the risk for influenza and its associated complications among pregnant and postpartum women, the low rates of influenza vaccination among pregnant women, and of antiviral treatment of women with ARFI admitted to obstetrics and gynecology wards. Increasing awareness of the prevalence of influenza ARFI among pregnant women, the use of empiric antiviral treatment for ARFI, and the infection control in obstetrics wards during influenza seasons might help reduce influenza-associated morbidity among pregnant and postpartum women.

Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021-2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy.

The diagnosis of paediatric pulmonary tuberculosis is difficult, especially in young infants who cannot expectorate sputum spontaneously. Breath testing has shown promise in diagnosing respiratory tract infections, but data on paediatric tuberculosis are limited. We performed a prospective cross-sectional study in Kenya in children younger than five years with symptoms of tuberculosis. We analysed exhaled breath with a hand-held battery-powered nose device. For data analysis, machine learning was applied using samples classified as positive (microbiologically confirmed) or negative (unlikely tuberculosis) to assess diagnostic accuracy. Breath analysis was performed in 118 children. The area under the curve of the optimal model was 0.73. At a sensitivity of 86 % (CI 62-96 %), this resulted in a specificity of 42 % (95 % CI 30-55 %). Exhaled breath analysis shows promise as a triage test for TB in young children, although the WHO target product characteristics were not met.

OBJECTIVES: CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples. METHODS: CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020-2021) and KEQAS (2020-2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%). RESULTS: Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from -29.28 to 9.86 %, into -0.09-0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from -23.78 to 2.00 % pre-harmonization to -3.13-1.42 % post-harmonization. CONCLUSIONS: The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs.

Human cases of avian influenza virus (AIV) infections are associated with an age-specific disease burden. As the influenza virus N2 neuraminidase (NA) gene was introduced from avian sources during the 1957 pandemic, we investigate the reactivity of N2 antibodies against A(H9N2) AIVs. Serosurvey of healthy individuals reveal the highest rates of AIV N2 antibodies in individuals aged ≥65 years. Exposure to the 1968 pandemic N2, but not recent N2, protected against A(H9N2) AIV challenge in female mice. In some older adults, infection with contemporary A(H3N2) virus could recall cross-reactive AIV NA antibodies, showing discernable human- or avian-NA type reactivity. Individuals born before 1957 have higher anti-AIV N2 titers compared to those born between 1957 and 1968. The anti-AIV N2 antibodies titers correlate with antibody titers to the 1957 N2, suggesting that exposure to the A(H2N2) virus contribute to this reactivity. These findings underscore the critical role of neuraminidase immunity in zoonotic and pandemic influenza risk assessment.

For microbiological confirmation of pediatric pulmonary tuberculosis (PTB), gastric aspirates (GA) are often operationally unfeasible without hospitalization, and the encapsulated orogastric string test is not easily swallowed in young children. The Combined-NasoGastric-Tube-and-String-Test (CNGTST) enables dual collection of GA and string specimens. In a prospective cohort study in Kenya, we examined its feasibility in children under five with presumptive PTB and compared the bacteriological yield of string to GA. Paired GA and string samples were successfully collected in 95.6 % (281/294) of children. Mycobacterium tuberculosis was isolated from 7.0 % (38/541) of GA and 4.3 % (23/541) of string samples, diagnosing 8.2 % (23/281) of children using GA and 5.3 % (15/281) using string. The CNGTST was feasible in nearly all children. Yield from string was two-thirds that of GA despite a half-hour median dwelling time. In settings where the feasibility of hospitalisation for GA is uncertain, the string component can be used to confirm PTB.

The tenth Ebola Virus Disease (EVD) outbreak (2018-2020, North Kivu, Ituri, South Kivu) in the Democratic Republic of the Congo (DRC) was the second-largest EVD outbreak in history. During this outbreak, Ebola vaccination was an integral part of the EVD response. We evaluated community perceptions toward Ebola vaccination and identified correlates of Ebola vaccine uptake among high-risk community members in North Kivu, DRC. In March 2021, a cross-sectional survey among adults was implemented in three health zones. We employed a sampling approach mimicking ring vaccination, targeting EVD survivors, their household members, and their neighbors. Outbreak experiences and perceptions toward the Ebola vaccine were assessed, and modified Poisson regression was used to identify correlates of Ebola vaccine uptake among those offered vaccination. Among the 631 individuals surveyed, most (90.2%) reported a high perceived risk of EVD and 71.6% believed that the vaccine could reduce EVD severity; however, 63.7% believed the vaccine had serious side effects. Among the 474 individuals who had been offered vaccination, 397 (83.8%) received the vaccine, 180 (45.3%) of those vaccinated received the vaccine after two or more offers. Correlates positively associated with vaccine uptake included having heard positive information about the vaccine (RR 1.30, 95% CI 1.06-1.60), the belief that the vaccine could prevent EVD (RR 1.23, 95% CI 1.09-1.39), and reporting that religion influenced all decisions (RR 1.13, 95% CI 1.02-1.25). Ebola vaccine uptake was high in this population, although mixed attitudes and vaccine delays were common. Communicating positive vaccine information, emphasizing the efficacy of the Ebola vaccine, and engaging religious leaders to promote vaccination may aid in increasing Ebola vaccine uptake during future outbreaks.

BACKGROUND: Influenza vaccination coverage is low among persons with non-communicable diseases (NCDs) in China. Chinese health workers (HWs) do not routinely recommend influenza vaccination despite evidence that recommendations increase vaccine uptake. This study aims to assess whether interventions increased primary care HWs' recommendation for influenza vaccination and measure their impact on influenza vaccine uptake in persons with NCDs. METHODS: We conducted a cluster randomized controlled study in public primary healthcare clinics in Hubei from November 2018 through April 2019. In the intervention clinics, primary care HWs received training on the benefits of influenza vaccination and were asked to recommend influenza vaccine in routine primary healthcare for persons with NCDs. In the control clinics, primary care HWs did not receive training and provided standard services. We conducted questionnaire surveys before and after the intervention to collect information about recommendations made and receipt of influenza vaccines. RESULTS: A total of 896 primary care HWs and 4552 persons with NCDs were included. After intervention, a higher percentage of HWs recommended influenza vaccines in intervention clinics compared to control clinics. Vaccinated primary care HWs were more likely to recommend vaccination. Persons with NCDs reported higher influenza vaccination coverage in intervention than control clinics, and primary care HWs' recommendation increased vaccination uptake among persons with NCDs. CONCLUSIONS: Vaccinated primary care HWs were more likely to recommend influenza vaccination than unvaccinated HWs. Promoting primary care HWs' vaccination and encouraging them to recommend influenza vaccination during routine primary healthcare could increase influenza vaccine receipt among persons with NCDs. Registration number ChiCTR2200067140.

OBJECTIVE: :COVID-19 and related disruptions led to a significant decline in HIV diagnoses in the US in 2020. A previous analysis estimated 18% fewer diagnoses than expected among persons with HIV (PWH) acquiring infection in 2019 or earlier, suggesting that the decline in overall diagnoses cannot be attributed solely to decreased transmission. This analysis evaluates the progress made towards closing the 2020 diagnosis deficit in 2021. METHODS: :We apply previously developed methods analyzing 2021 diagnosis data from the National HIV Surveillance System to determine whether 2021 diagnosis levels of PWH infected pre2020 are above or below the expected pre-COVID trends. Results are stratified by assigned sex at birth, transmission group, geographic region, and race/ethnicity. RESULTS: :In 2021, HIV diagnoses returned to pre-COVID levels among all PWH acquiring infection 2011-19. Among Hispanic/Latino PWH and males, diagnoses returned to pre-COVID levels. White PWH, men who have sex with men, and PWH living in the south and northeast showed higher-than-expected levels of diagnosis in 2021. For the remaining populations, there were fewer HIV diagnoses in 2021 than expected. CONCLUSIONS: :While overall diagnoses among persons acquiring HIV pre2020 returned to pre-COVID levels, the diagnosis gap observed in 2020 remained unclosed at the end of 2021. Fewer than expected diagnoses among certain populations indicate that COVID-19 related disruptions to HIV diagnosis trends remained in 2021. Although some groups showed higher-than-expected levels of diagnoses, such increases were smaller than corresponding 2020 decreases. Expanded testing programs designed to close these gaps are essential.

OBJECTIVE: Assessing mobility among people with HIV is an important consideration when measuring HIV incidence, prevalence, and the care continuum in the United States. Our aims were to measure mobility among people with HIV compared with the general population and to examine factors associated with migration among people with HIV. METHODS: We calculated state-to-state move-in and move-out migration rates for 2011 through 2019 using National HIV Surveillance System data for people with HIV and using US Census data for the general population. For people with HIV, we also assessed the association between migration and HIV care outcomes. RESULTS: From 2011 through 2019, the US general population had stable migration, whereas migration rates among people with HIV fluctuated and were higher than among the general population. Among people with HIV, migration rates in 2019 were higher among people assigned male sex at birth versus female sex at birth, among people aged ≤24 years versus ≥25 years, among people with HIV infection attributed to male-to-male sexual contact versus other transmission categories, and among non-Hispanic Other people (ie, American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or multiple races) versus Hispanic, non-Hispanic Black, and non-Hispanic White people. Receipt of HIV medical care (90.3% vs 75.5%) and achieving viral suppression (72.1% vs 65.3%) were higher among people with HIV who migrated versus those who did not. CONCLUSIONS: People with HIV in the United States are more mobile than the general population. Determining the mobility of people with HIV can help with strategic allocation of HIV prevention and care resources.

BACKGROUND: Whether the COVID-19 pandemic has had a disproportionate impact on mortality among persons with diagnosed HIV (PWDH) in United States is unclear. Through our macro-scale analysis, we seek to better understand how the COVID-19 pandemic affected mortality among PWDH. METHODS: We obtained mortality and population data for the years 2018-2020 from the National HIV Surveillance System (NHSS) for the U.S. PWDH population, and from publicly available data for the general population. We computed mortality rates and excess mortality for both the general and PWDH populations. Stratifications by age, race/ethnicity, and sex were considered. For each group, we determined whether the 2020 mortality rates and mortality risk ratio showed a statistically significant change from 2018-2019. RESULTS: Approximately 1550 excess deaths occurred among PWDH in 2020, with Black, Hispanic/Latino and PWDH 55 and older comprising the majority of excess deaths. Mortality rates increased in 2020 from 2018-2019 across the general population in all groups. Among PWDH, mortality rates either increased, or showed no statistically significant change. These increases were similar to, or smaller than, those observed in the general population, resulting in a 7.7% decrease in the mortality risk ratio between PWDH and the general population. CONCLUSIONS: While mortality rates among PWDH increased in 2020 relative to 2018-2019, the increases were smaller, or of similar magnitude, to those observed in the general population. We thus do not find evidence of elevated mortality risk from the COVID-19 pandemic among PWDH. These findings held across subpopulations stratified by age, sex, and racial/ethnic group.

CONTEXT: Public health policy can play an important role in improving public health outcomes. Accordingly, there has been an increasing emphasis by policy makers on identifying and implementing evidence-informed public health policy interventions. PROGRAM OR POLICY: Growth and refinement of the field of research assessing the impact of legal interventions on health outcomes, known as legal epidemiology, prompted this review of studies on the relationship between laws and health or economic outcomes. IMPLEMENTATION: Authors systematically searched 8 major literature databases for all English language journal articles that assessed the effect of a law on health and economic outcomes published between January 1, 2009, and September 18, 2019. This search generated 12 570 unique articles 177 of which met inclusion criteria. The team conducting the systematic review was a multidisciplinary team that included health economists and public health policy researchers, as well as public health lawyers with expertise in legal epidemiological research methods. The authors identified and assessed the types of methods used to measure the laws' health impact. EVALUATION: In this review, the authors examine how legal epidemiological research methods have been described in the literature as well as trends among the studies. Overall, 3 major themes emerged from this study: (1) limited variability in the sources of the health data across the studies, (2) limited differences in the methodological approaches used to connect law to health outcomes, and (3) lack of transparency surrounding the source and quality of the legal data relied upon. DISCUSSION: Through highlighting public health law research methodologies, this systematic review may inform researchers, practitioners, and lawmakers on how to better examine and understand the impacts of legal interventions on health and economic outcomes. Findings may serve as a source of suggested practices in conducting legal epidemiological outcomes research and identifying conceptual and method-related gaps in the literature.

OBJECTIVE(S): To examine associations between Index of Concentration at the Extremes (ICE) measures for economic and racial segregation and HIV outcomes in the United States (U.S.) and Puerto Rico. METHODS: County-level HIV testing data from CDC's National HIV Prevention Program Monitoring and Evaluation and census tract-level HIV diagnoses, linkage to HIV medical care, and viral suppression data from the National HIV Surveillance System were used. Three ICE measures of spatial polarization were obtained from the U.S. Census Bureau's American Community Survey: ICEincome (income segregation), ICErace (Black-White racial segregation), and ICEincome+race (Black-White racialized economic segregation). Rate ratios (RRs) for HIV diagnoses and prevalence ratios (PRs) for HIV testing, linkage to care within 1 month of diagnosis, and viral suppression within 6 months of diagnosis were estimated with 95% confidence intervals (CIs) to examine changes across ICE quintiles using the most privileged communities (Quintile 5, Q5) as the reference group. RESULTS: PRs and RRs showed a higher likelihood of testing and adverse HIV outcomes among persons residing in Q1 (least privileged) communities compared with Q5 (most privileged) across ICE measures. For HIV testing percentages and diagnosis rates, across quintiles, PRs and RRs were consistently greatest for ICErace. For linkage to care and viral suppression, PRs were consistently lower for ICEincome+race. CONCLUSIONS: We found that poor HIV outcomes and disparities were associated with income, racial, and economic segregation as measured by ICE. These ICE measures contribute to poor HIV outcomes and disparities by unfairly concentrating certain groups (i.e., Black persons) in highly segregated and deprived communities that experience a lack of access to quality, affordable health care. Expanded efforts are needed to address the social/economic barriers that impede access to HIV care among Black persons. Increased partnerships between government agencies and the private sector are needed to change policies that promote and sustain racial and income segregation.

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

INTRODUCTION: During the 2018-2020 Ebola virus disease (EVD) outbreak in the eastern part of the Democratic Republic of the Congo (DRC), prevention and control measures, such as Ebola vaccination were challenging by community mistrust. We aimed to understand perceptions regarding Ebola vaccination and identify determinants of Ebola vaccine uptake among HCWs. METHODS: In March 2021, we conducted a cross-sectional survey among 438 HCWs from 100 randomly selected health facilities in three health zones (Butembo, Beni, Mabalako) affected by the 10th EVD outbreak in North Kivu, DRC. HCWs were eligible if they were ≥ 18 years and were working in a health facility during the outbreak. We used survey logistic regression to assess correlates of first-offer uptake (i.e., having received the vaccine the first time it was offered vs. after subsequent offers). RESULTS: Of the 438 HCWs enrolled in the study, 420 (95.8%) reported that they were eligible and offered an Ebola vaccine. Among those offered vaccination, self-reported uptake of the Ebola vaccine was 99.0% (95% confidence interval (CI) [98.5-99.4]), but first-offer uptake was 70.2% (95% CI [67.1, 73.5]). Nearly all HCWs (94.3%; 95% CI [92.7-95.5]) perceived themselves to be at risk of contracting EVD. The most common concern was that the vaccine would cause side effects (65.7%; 95% CI [61.4-69.7]). In the multivariable analysis, mistrust of the vaccine source or how the vaccine was produced decreased the odds of first-time uptake. DISCUSSION: Overall uptake of the Ebola vaccine was high among HCWs, but uptake at the first offer was substantially lower, which was associated with mistrust of the vaccine source. Future Ebola vaccination efforts should plan to make repeated vaccination offers to HCWs and address their underlying mistrust in the vaccines, which can, in turn, improve community uptake.

The evolutionary histories of the antibiotic-resistant Streptococcus pneumoniae lineages PMEN3 and PMEN9 were reconstructed using global collections of genomes. In PMEN3, one resistant clade spread worldwide, and underwent 25 serotype switches, enabling evasion of vaccine-induced immunity. In PMEN9, only 9 switches were detected, and multiple resistant lineages emerged independently and circulated locally. In Germany, PMEN9’s expansion correlated significantly with the macrolide:penicillin consumption ratio. These isolates were penicillin sensitive but macrolide resistant, through a homologous recombination that integrated Tn1207.1 into a competence gene, preventing further diversification via transformation. Analysis of a species-wide dataset found 183 acquisitions of macrolide resistance, and multiple gains of the tetracycline-resistant transposon Tn916, through homologous recombination, often originating in other streptococcal species. Consequently, antibiotic selection preserves atypical recom- bination events that cause sequence divergence and structural variation throughout the S. pneumoniae chromosome. These events reveal the genetic exchanges between species normally counter-selected until perturbed by clinical interventions.Competing Interest StatementNJC has consulted for Antigen Discovery Inc. NJC has received an investigator-initiated award from GlaxoSmithKline.

Objective(s): To examine associations between Index of Concentration at the Extremes (ICE) measures for economic and racial segregation and HIV outcomes in the United States (U.S.) and Puerto Rico. Method(s): County-level HIV testing data from CDC's National HIV Prevention Program Monitoring and Evaluation and census tract-level HIV diagnoses, linkage to HIV medical care, and viral suppression data from the National HIV Surveillance System were used. Three ICE measures of spatial polarization were obtained from the U.S. Census Bureau's American Community Survey: ICEincome (income segregation), ICErace (Black-White racial segregation), and ICEincome+race (Black-White racialized economic segregation). Rate ratios (RRs) for HIV diagnoses and prevalence ratios (PRs) for HIV testing, linkage to care within 1 month of diagnosis, and viral suppression within 6 months of diagnosis were estimated with 95% confidence intervals (CIs) to examine changes across ICE quintiles using the most privileged communities (Quintile 5, Q5) as the reference group. Result(s): PRs and RRs showed a higher likelihood of testing and adverse HIV outcomes among persons residing in Q1 (least privileged) communities compared with Q5 (most privileged) across ICE measures. For HIV testing percentages and diagnosis rates, PRs and RRs were consistently greatest for ICErace. For linkage to care and viral suppression, PRs were consistently lower for ICEincome+race. Conclusion(s): Income, racial, and economic segregation-as measured by ICE-might contribute to poor HIV outcomes and disparities by unfairly concentrating certain groups (i.e., Black persons) in highly segregated and deprived communities that experience a lack of access to quality, affordable health care. Expanded efforts are needed to address the social/economic barriers that might impede access to HIV care among Black persons. Increased partnerships between government agencies and the private sector are needed to change policies that promote and sustain racial and income segregation. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Background: Whether COVID-19 has had a disproportionate impact on mortality among persons with diagnosed HIV (PWDH) in United States is unclear. Through our macro-scale analysis, we seek to better understand how COVID-19 and subsequent behavioral changes affected mortality among PWDH. Method(s): We obtained mortality and population size data for the years 2018-2020 from the National HIV Surveillance System (NHSS) for the PWDH population aged >=13 years in the United States, and from publicly available data for the general population. We computed mortality rates and excess mortality for both the general and PWDH populations. Stratifications by age, race/ethnicity, and sex-at birth were considered. For each group, we determined whether the 2020 mortality rates and mortality risk ratio showed a statistically significant change from 2018-2019. Result(s): Mortality rates increased in 2020 from 2018-2019 across the general population in all groups. Among PWDH, mortality rates either increased, or showed no statistically significant change. The mortality risk ratio between PWDH and the general population decreased 7.7% in 2020. Approximately 1550 excess deaths occurred among PWDH in 2020, with Black, Hispanic/Latino and PWDH above 55 and older representing the majority of excess deaths. Conclusion(s): While mortality rates among PWDH increased in 2020 relative to 2018-2019, the increases were smaller than those observed in the general population. This suggests that COVID-19 and resulting behavioral changes among PWDH did not result in disproportionate mortality among PWDH. These findings suggest that COVID-19, and any associated indirect effects, do not represent a proportionally greater risk for PWDH compared to the general population. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Background: Diagnoses of HIV in the US decreased by 17% in 2020 due to COVID-related disruptions. The extent to which this decrease is attributable to changes in HIV testing versus HIV transmission is unclear. We seek to better understand this issue by analyzing the discrepancy in expected versus observed HIV diagnoses in 2020 among persons who acquired HIV between 2010-2019, as changes in diagnosis patterns in this cohort cannot be attributed to changes in transmission. Method(s): We developed three methods based on the CD4-depletion model to estimate excess missed diagnoses in 2020 among persons with HIV (PWH) infected from 2010-2019. We stratified the results by transmission group, sex assigned at birth, race/ethnicity, and region to examine differences by group and confirm the reliability of our estimates. We performed similar analyses projecting diagnoses in 2019 among PWH infected from 2010-2018 to evaluate the accuracy of our methods against surveillance data. Result(s): There were approximately 3100-3300 (approximately 18%) fewer diagnoses than expected in 2020 among PWH infected from 2010-2019. Females (at birth), heterosexuals, persons who inject drugs, and Hispanic/Latino PWH missed diagnoses at higher levels than the overall population. Validation and stratification analyses confirmed the accuracy and reliability of our estimates. Conclusion(s): The substantial drop in number of previously infected PWH diagnosed in 2020, suggests that changes in testing played a substantial role in the observed decrease. Levels of missed diagnoses differed substantially across population subgroups. Increasing testing efforts and innovative strategies to reach undiagnosed PWH are needed to offset this diagnosis gap. These analyses may be used to inform future estimates of HIV transmission during the COVID-19 pandemic. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Characterizing airborne pollen concentrations is crucial for supporting allergy and asthma management; however, pollen monitoring is labor intensive and, in the USA, geographically limited. The USA National Phenology Network (USA-NPN) engages thousands of volunteer observers in regularly documenting the developmental and reproductive status of plants. The reports of flower and pollen cone status contributed to the USA-NPN's platform, Nature's Notebook, have the potential to help address gaps in pollen monitoring by providing real-time, spatially explicit information from across the country. In this study, we assessed whether observations of flower and pollen cone status contributed to Nature's Notebook can serve as effective proxies for airborne pollen concentrations. We compared daily pollen concentrations from 36 National Allergy Bureau (NAB) stations in the USA with flowering and pollen cone status observations collected within 200 km of each NAB station in each year, 2009-2021, for 15 common tree taxa using Spearman's correlations. Of 350 comparisons, 58% of correlations were significant (p < 0.05). Comparisons could be made at the largest numbers of sites for Acer and Quercus. Quercus demonstrated a comparatively high proportion of tests with significant agreement (median ρ = 0.49). Juglans demonstrated the strongest overall coherence between the two datasets (median ρ = 0.79), though comparisons were made at only a small number of sites. For particular taxa, volunteer-contributed flowering status observations demonstrate promise to indicate seasonal patterns in airborne pollen concentrations. The quantity of observations, and therefore, their utility for supporting pollen alerts, could be substantially increased through a formal observation campaign.

Populations affected by humanitarian crises and emerging infectious disease outbreaks may have unique concerns and experiences that influence their perceptions toward vaccines. In March 2021, we conducted a survey to examine the perceptions toward COVID-19 vaccines and identify the factors associated with vaccine intention among 631 community members (CMs) and 438 healthcare workers (HCWs) affected by the 2018-2020 Ebola Virus Disease outbreak in North Kivu, Democratic Republic of the Congo. A multivariable logistic regression was used to identify correlates of vaccine intention. Most HCWs (81.7%) and 53.6% of CMs felt at risk of contracting COVID-19; however, vaccine intention was low (27.6% CMs; 39.7% HCWs). In both groups, the perceived risk of contracting COVID-19, general vaccine confidence, and male sex were associated with the intention to get vaccinated, with security concerns preventing vaccine access being negatively associated. Among CMs, getting the Ebola vaccine was associated with the intention to get vaccinated (RR 1.43, 95% CI 1.05-1.94). Among HCWs, concerns about new vaccines' safety and side effects (OR 0.72, 95% CI 0.57-0.91), religion's influence on health decisions (OR 0.45, 95% CI 0.34-0.61), security concerns (OR 0.52, 95% CI 0.37-0.74), and governmental distrust (OR 0.50, 95% CI 0.35-0.70) were negatively associated with vaccine perceptions. Enhanced community engagement and communication that address this population's concerns could help improve vaccine perceptions and vaccination decisions. These findings could facilitate the success of vaccine campaigns in North Kivu and similar settings.

Diagnosis of tuberculosis (TB) among young children (<5 years) is challenging due to the paucibacillary nature of clinical disease and clinical similarities to other childhood diseases. We used machine learning to develop accurate prediction models of microbial confirmation with simply defined and easily obtainable clinical, demographic, and radiologic factors. We evaluated eleven supervised machine learning models (using stepwise regression, regularized regression, decision tree, and support vector machine approaches) to predict microbial confirmation in young children (<5 years) using samples from invasive (reference-standard) or noninvasive procedure. Models were trained and tested using data from a large prospective cohort of young children with symptoms suggestive of TB in Kenya. Model performance was evaluated using areas under the receiver operating curve (AUROC) and precision-recall curve (AUPRC), accuracy metrics. (i.e., sensitivity, specificity), F-beta scores, Cohen's Kappa, and Matthew's Correlation Coefficient. Among 262 included children, 29 (11%) were microbially confirmed using any sampling technique. Models were accurate at predicting microbial confirmation in samples obtained from invasive procedures (AUROC range: 0.84-0.90) and from noninvasive procedures (AUROC range: 0.83-0.89). History of household contact with a confirmed case of TB, immunological evidence of TB infection, and a chest x-ray consistent with TB disease were consistently influential across models. Our results suggest machine learning can accurately predict microbial confirmation of M. tuberculosis in young children using simply defined features and increase the bacteriologic yield in diagnostic cohorts. These findings may facilitate clinical decision making and guide clinical research into novel biomarkers of TB disease in young children.

We recently read the article of Song et al. on human biomonitoring of urinary metabolites of neonicotinoids with high interest.1 Our own experiments2 on the metabolism of imidacloprid after a single oral dose of 5 mg in a male volunteer do confirm the findings of Song and co-workers that 5-hydroxyimidacloprid (5-OH-IMI) and imidacloprid olefin are relevant metabolites of imidacloprid in humans. Unfortunately, the article, like several others, has a serious shortcoming from an analytical point of view. | | The metabolism of imidacloprid has previously been described in sufficient detail in mammals;3,4 whereas data in humans are scarce and mostly qualitative.5 Available studies indicate that 5-OH-IMI is a major specific metabolite of imidacloprid; however, not just any 5-OH-IMI but one that is hydroxylated at the 1H-imidazol moiety (1, CAS no. 155802–61–2). Therefore, using the correct 5-OH-IMI standard material for chemical analyses for human biomonitoring of imidacloprid is a critical first step. For example, in preparation for our controlled studies in humans, we had to synthesize 1 and a 13C2, 15N isotope labeled analogue because the substances were not commercially available at that time.

In their Correspondence, Xue and Bloom1 identify an important discrepancy in the sequence data that we provided in our 2016 paper2 on the transmission of influenza virus in Hong Kong during the first wave of the H1N1 pandemic in 2009. The goal of the study was to provide a quantitative approach to characterizing the within-host genetic diversity of influenza virus and how this genomic information might be used in tracking transmission. We have determined that the potential source of this discrepancy was due to the technical limitations of the methods used at the time, which inadvertently led to the reporting of substantially higher levels of within-host diversity than were likely to be present.

Considering the hazardous effects of particulate matter (PM) exposure on students and teachers and the high PM concentration issue in South Korea, air purifiers have recently been installed in most classrooms to improve air quality. However, some on-site challenges, such as operational costs and noise, have been issues with the continuous operation of air purifiers. Therefore, a guideline is needed to dynamically predict the indoor PM concentration based on the changes in outdoor PM concentration and activate the air purifiers only when necessary. This study develops a grey-box model that uses measured data and physical differential equations to perform the given objective and verifies its accuracy using ASTM D5157. Modeling and analysis results have obtained information that can form the basis for developing guidelines to address PM issues in schools: The air purifier should be operated during periods where the predicted values exceed the limit in closed windows and the air purifier is not operating. It was also confirmed that the need for the operation of the air purifier varies between schools and classrooms under the same outdoor PM concentration. Indoor PM concentration increased significantly after students' simultaneous mass movement, necessitating air purifiers' operation before and after the events. The pre-filter of the heater also aided in the removal of coarse PM. Additionally, the limitations and future development directions of the model were discussed.

Navi Mumbai Municipal Corporation (NMMC), a local government in Mumbai, India, implemented the first public sector TCV campaign in 2018. This study estimated the delivery costs of this TCV campaign using a Microsoft Excel-based tool based on a micro-costing approach from the government (NMMC) perspective. The campaign's financial (direct expenditures) and economic costs (financial costs plus the monetized value of additional donated or existing items) incremental to the existing immunization program were collected. The data collection methods involved consultations with NMMC staff, reviews of financial and programmatic records of NMMC and the World Health Organization (WHO), and interviews with the health staff of sampled urban health posts (UHPs). Three UHPs were purposively sampled, representing the three dominant residence types in the catchment area: high-rise, slum, and mixed (high-rise and slum) areas. The high-rise area UHP had lower vaccination coverage (47%) compared with the mixed area (71%) and slum area UHPs (76%). The financial cost of vaccine and vaccination supplies (syringes, safety boxes) was $1.87 per dose, and the economic cost was $2.96 per dose in 2018 US dollars. Excluding the vaccine and vaccination supplies cost, the financial delivery cost across the 3 UHPs ranged from $0.37 to $0.53 per dose, and the economic delivery cost ranged from $1.37 to $3.98 per dose, with the highest delivery costs per dose in the high-rise areas. Across all 11 UHPs included in the campaign, the weighted average financial delivery cost was $0.38 per dose, and the economic delivery cost was $1.49 per dose. WHO has recommended the programmatic use of TCV in typhoid-endemic countries, and Gavi has included TCV in its vaccine portfolio. This first costing study of large-scale TCV introduction within a public sector immunization program provides empirical evidence for policymakers, stakeholders, and future vaccine campaign planning.

BACKGROUND: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. METHODS: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. FINDINGS: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. INTERPRETATION: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. FUNDING: WHO, US National Institutes of Health.

Objective: Paid sick leave (PSL) laws mandate employers give workers paid time off when they are sick or injured. This current study aims to examine whether access to PSL is associated with healthcare utilization and health outcomes and to summarize the types of utilization and outcomes which have been reported to be associated with PSL. Methods: We conducted a rapid evidence review. Our search of seven databases, including Medline, Embase, PsycINFO, Cochrane Library, CINAHL, Scopus, and JSTOR, on September 21, 2020, identified 757 studies, 30 of which were retained. Results: Previous evidence is mostly provided by cross-sectional studies with survey data. In this study, evidence suggests that PSL is significantly associated with some types of healthcare utilization and health outcomes. In terms of healthcare utilization, findings indicate PSL is associated with an increase in the use of some preventive services and a decrease in the use of emergency care; while findings are mixed regarding associations of PSL with health provider visits and the use of mammograms and pap smears. As for health outcomes, findings suggest PSL is associated with improved mental and self-rated health, decreased incidence of influenza-like illness, and lower occupational injuries and mortality rates. Conclusion: PSL may be an effective tool in improving some healthcare utilization and health outcomes. Future research could help identify mechanisms through which PSL access works and identify what policy components lead to better outcomes. © 2023