Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2(nd) most accurate model measured by WIS in 2021-22 and the 5(th) most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

BACKGROUND: Understanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population. METHODS: An observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay. RESULTS: The median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt. CONCLUSIONS: These findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

National Public Health Institutes (NPHIs) can strengthen countries' public health capacities to prevent, detect, and respond to public health emergencies. This qualitative evaluation assessed the role of the US Centers for Disease Control and Prevention (CDC) in NPHI development and strengthening of public health functions. We interviewed NPHI staff (N = 43), non-NPHI government staff (N = 29), and non-governmental organization staff (N = 24) in seven countries where CDC has supported NPHI development: Cambodia, Colombia, Liberia, Mozambique, Nigeria, Rwanda, and Zambia. Participants identified four areas of support that were the most important: workforce capacity building, technical assistance for key public health functions, identifying institutional gaps and priorities, and funding to support countries' priorities. Participants underscored the need for capacity building directed toward country-driven priorities during planning and implementation. Continued support for NPHI development from CDC and other partners is vital to building stronger public health systems, improving population health, and strengthening global health security.

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

The immunopathogenesis of inflammatory bowel disease (IBD) has been attributed to a combination of host genetics and intestinal dysbiosis. Previous work in a small cohort of IBD patients suggested that pro-inflammatory bacterial taxa are highly coated with secretory immunoglobulin IgA. Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), we profiled IgA coating of intestinal microbiota in a large cohort of IBD patients and identified bacteria associated with disease and treatment. Forty-three bacterial taxa displayed significantly higher IgA coating in IBD compared with controls, including 8 taxa exhibiting differential IgA coating but similar relative abundance. Patients treated with anti-TNF-α therapies exhibited dramatically altered microbiota-specific IgA responses compared with controls. Furthermore, increased IgA coating of Oscillospira was associated with a delay in time to surgery. These results demonstrate that investigating IgA responses to microbiota can uncover potential disease-modifying taxa and reveal improved biomarkers of clinical course in IBD.

National Public Health Institutes (NPHIs) are national-level institutions that can lead and coordinate a country's public health system. The Africa Centres for Disease Control and Prevention (Africa CDC) considers NPHI development critical to strengthening public health systems in Africa. This paper describes how Joint External Evaluation (JEE) reports demonstrate the role NPHIs can play in supporting the goals of IHR compliance and global health security. This study is a secondary document-based qualitative analysis of JEE reports from 11 countries in the WHO AFRO region (Botswana, Ethiopia, Liberia, Mozambique, Namibia, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, and Zambia). Researchers found three distinct thematic areas: i) core public health functions, ii) governance, and iii) coordination, collaboration, and communication. These themes and their interlinkages, both in pairs and all three, were of importance in displaying the roles that NPHIs could play in the strengthening of health systems. The data suggests that NPHIs, though not always explicitly mentioned in the data, may have a vital role in strengthening health systems across Africa and their governments' goals of achieving IHR compliance.

INTRODUCTION: Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease. As part of a public health investigation of a manufacturing facility, we performed paired environmental and human sampling to evaluate cross-pollination of microbes between environment and host and possible effects on lung pathology present among workers. METHODS: Workplace environmental microbiota was evaluated in air and MWF samples. Human microbiota was evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, lung tissue controls, and in skin, nasal and oral samples from 302 workers from different areas of the facility. In vitro effects of MWF exposure on murine B-cells were assessed. RESULTS: Increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared to controls. Among workers in different locations within the facility, those that worked in machine shop area had skin, nasal and oral microbiota more closely related to the microbiota present in MWF samples. Lung samples from four index cases, and skin and nasal samples from workers in machine shop area were enriched with Pseudomonas, the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation in vitro, a hallmark cell subtype found in pathology of index cases. CONCLUSIONS: Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard.

In the presence of health threats, precision public health approaches aim to provide targeted, timely, and population-specific interventions. Accurate surveillance methodologies that can estimate infectious disease activity ahead of official healthcare-based reports, at relevant spatial resolutions, are important for achieving this goal. Here we introduce a methodological framework which dynamically combines two distinct influenza tracking techniques, using an ensemble machine learning approach, to achieve improved state-level influenza activity estimates in the United States. The two predictive techniques behind the ensemble utilize (1) a self-correcting statistical method combining influenza-related Google search frequencies, information from electronic health records, and historical flu trends within each state, and (2) a network-based approach leveraging spatio-temporal synchronicities observed in historical influenza activity across states. The ensemble considerably outperforms each component method in addition to previously proposed state-specific methods for influenza tracking, with higher correlations and lower prediction errors.

On July 28, 2014, the Cincinnati Health Department was notified of suspected cases of foodborne botulism in two women admitted to the same hospital 12 days apart. Patient A had been treated for 12 days for suspected autoimmune disease. When patient B, the roommate of patient A, was evaluated at the same medical center for similar symptoms, it was learned that on July 13, patient A and patient B had shared a meal that included prepackaged pesto from a jar; clinicians suspected botulism and notified the local health department. The pesto had been purchased from company A's farm stand in San Clemente, California. Laboratory testing detected botulinum toxin type B by enzyme-linked immunosorbent assay (ELISA) in leftovers of pasta with pesto. A culture of these food samples yielded Clostridium spp. that produced botulinum toxin type B; polymerase chain reaction (PCR) testing also was positive for type B toxin gene. Environmental assessment of company A identified improper acidification and pressurization practices and lack of licensure to sell canned products commercially, including products in hermetically-sealed jars. On July 30, the vendor voluntarily recalled all jarred products, and the California Department of Public Health (CDPH) warned the public not to consume company A's jarred foods. This report describes the two cases and the public health investigation that traced the source of the outbreak.

OBJECTIVE: To analyze the prevalence of acute asymptomatic group A and C rotavirus (RV-A and RV-C) infection in neonates with cholestasis. STUDY DESIGN: Participants were infants <180 days of age with cholestasis (serum direct or conjugated bilirubin >20% of total and ≥2 mg/dL) enrolled in the Childhood Liver Disease Research and Education Network during RV season (December-May). Forty infants with biliary atresia (BA), age 62 +/- 29 days (range, 4.7-13 weeks) and 38 infants with cholestasis, age 67 +/- 44 days (range, 3-15.8 weeks) were enrolled. RESULTS: At enrollment, RV-A IgM positivity rates did not differ between infants with BA (10%) vs those without (18%) (P = .349). RV-C IgM was positive in 0% of infants with BA vs 3% in those without BA (P = .49). RV-A IgG was lower in infants with BA: 51 +/- 39 vs 56 +/- 44 enzyme-linked immunoassay unit, P = .045 but this difference may lack biological relevance as maternal RV-A IgG titers were similar between groups. Infant RV-A IgM titers at 2-6 months follow-up increased markedly vs at presentation in both infants with BA (50 +/- 30 vs 9 +/- 9) and those without (43 +/- 18 vs 16 +/- 20 enzyme-linked immunoassay unit) (P < .0001), without differences between groups. CONCLUSIONS: RV-A infection in the first 6 months of life is common in infants with cholestasis of any cause. RV-A could have different pathogenetic effects by initiating different hepatic immune responses in infants with vs without BA or could lack pathogenetic significance.

OBJECTIVES: To examine associations of homophobia, racism, and resiliency with differences in prevalent HIV infection in black and white MSM. METHODS: The Involve[ment]t study is a cohort of black and white MSM aged 18-39 years in Atlanta, GA designed to evaluate individual, dyadic, and community level factors that might explain racial disparities in HIV prevalence. Participants were recruited irrespective of HIV serostatus from community-based venues and from Internet ads and were tested for HIV. We assessed respondents' demographics, whether they had engage in unprotected anal intercourse (UAI) within the past 6 months, and attitudes about perceived homophobia, perceived racism, and personal resiliency. RESULTS: Compared to white MSM, black MSM were less likely to report UAI in the past 6 months (OR = 0.59, CI = 0.44-0.80), more likely to be HIV-positive (OR = 5.05, CI = 3.52-7.25) and, among-those HIV-positive-more likely to report not being aware of their HIV infection (OR = 2.58, CI = 1.18-5.65). Greater perceived racism was associated with UAI in the black sample (partial odds ratio [pOR] = 1.48, CI = 1.10-1.99). Overall, perceived homophobia, perceived racism, and resilience were not associated with prevalent HIV infection in sample. Greater resilience was associated with less perceived homophobia in both black and white samples (Spearman r = -.27, p < .001, for both). CONCLUSION: Future studies of social discrimination at the institutional and network level, than at the individual level, may explain differences in HIV infection in black and white MSM.