OBJECTIVES: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high-burden settings, which have limited data, by comparing with RSV-positive and other cases. METHODS: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (adjusted OR [aOR]) were calculated using logistic regression. Aetiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics. RESULTS: hMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p ≤ 0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR, 0.18), especially RSV (aOR, 0.11; all p < 0.0001), and positively associated with the detection of bacteria (aORs, 1.77; p 0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value for hMPV aetiology was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than that among other cases (9.6%). DISCUSSION: HMPV-associated severe paediatric pneumonia in high-burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.

The increasing threat from infection with drug-resistant pathogens is among the most serious public health challenges of our time. Formed by Wellcome in 2018, the Surveillance and Epidemiology of Drug-Resistant Infections Consortium (SEDRIC) is an international think tank whose aim is to inform policy and change the way countries track, share, and analyse data relating to drug-resistant infections, by defining knowledge gaps and identifying barriers to the delivery of global surveillance. SEDRIC delivers its aims through discussions and analyses by world-leading scientists that result in recommendations and advocacy to Wellcome and others. As a result, SEDRIC has made key contributions in furthering global and national actions. Here, we look back at the work of the consortium between 2018-2024, highlighting notable successes. We provide specific examples where technical analyses and recommendations have helped to inform policy and funding priorities that will have real-world impact on the surveillance and epidemiology of infections with drug-resistant pathogens. | The increasing threat from infections that cannot be treated with medicines, so called drug resistant infections, is among the most serious public health challenges of our time. Formed by Wellcome in 2018, the Surveillance and Epidemiology of Drug-Resistant Infections Consortium (SEDRIC) is an international think tank whose aim is to inform policy and change the way countries track, share, and analyse data relating to drug-resistant infections, by defining knowledge gaps and identifying barriers to the delivery of global surveillance. SEDRIC delivers its aims through discussions and analyses by world-leading scientists that result in recommendations and advocacy to Wellcome and others. As a result, SEDRIC has made key contributions in furthering global and national actions. Here, we look back at the work of the consortium between 2018-2024, highlighting notable successes. We provide specific examples where technical analyses and recommendations have helped to inform policy and funding priorities that will have real-world impact on the surveillance and of infections with pathogens that are becoming difficult or impossible to treat. | eng

During 2023-2024, highly pathogenic avian influenza A(H5N1) viruses from clade 2.3.2.1c caused human infections in Cambodia and from clade 2.3.4.4b caused human infections in the Americas. We assessed the susceptibility of those viruses to approved and investigational antiviral drugs. Except for 2 viruses isolated from Cambodia, all viruses were susceptible to M2 ion channel-blockers in cell culture-based assays. In the neuraminidase inhibition assay, all viruses displayed susceptibility to neuraminidase inhibitor antiviral drugs oseltamivir, zanamivir, peramivir, laninamivir, and AV5080. Oseltamivir was ≈4-fold less potent at inhibiting the neuraminidase activity of clade 2.3.4.4b than clade 2.3.2.1c viruses. All viruses were susceptible to polymerase inhibitors baloxavir and tivoxavir and to polymerase basic 2 inhibitor pimodivir with 50% effective concentrations in low nanomolar ranges. Because drug-resistant viruses can emerge spontaneously or by reassortment, close monitoring of antiviral susceptibility of H5N1 viruses collected from animals and humans by using sequence-based analysis supplemented with phenotypic testing is essential.

We used statewide surveillance data to describe the epidemiology of invasive Haemophilus influenzae type a (Hia) disease in Alaska during 2018-2022. Of 52 cases identified, 39 (75%) occurred among Alaska Native children aged <5 years who lived in rural areas of southwest or northern Alaska. Average annual incidence was 17.8 per 100,000 among children aged <5 years compared to 0.3 per 100,000 among persons aged ≥5 years. Among 43 cases in children aged <5 years, 16 (37%) presented with meningitis and 6 (14%) died. Characterizing Hia disease epidemiology can help direct prevention strategies, including vaccine development and use.

BACKGROUND: We estimate annual viral influenza-associated mild-to-moderate illness, hospitalizations, and deaths in 6 South American countries (Argentina, Brazil, Chile, Ecuador, Paraguay, and Uruguay) during the 2015-2019 influenza seasons as a first step in evaluating the full value of influenza vaccination in the subregion. METHODS: We applied a multiplier method using monthly hospital discharge and vital statistics death records, influenza surveillance data, and population projections to estimate mild-to-moderate influenza-associated illness, hospitalizations, and deaths. We estimated the uncertainty bounds based on the 2.5th and 97.5th percentiles of the Monte Carlo simulated distributions for the number of cases and obtained the ranges from the minimum value of the 2.5th and the maximum value of the 97.5th percentile. RESULTS: In selected countries with a total population of 307 million people, the yearly influenza-associated burden of disease ranged between 51 and 78 million mild-to-moderate influenza illnesses, between 323 379 and 490 049 hospitalizations, and between 22 662 and 46 971 deaths during the 2015-2019 influenza seasons. CONCLUSIONS: Each year, influenza is associated with millions of illnesses, hundreds of thousands of hospitalizations, and tens of thousands of deaths in 6 South American countries, affecting a significant portion of the population. Such findings can be used to estimate the number of illnesses averted through vaccination programs and the cost-benefit of influenza vaccines.

During 2018-2022, a resurgence of hepatitis A occurred in Florida, with 5,491 cases reported. Genotyping was performed on a convenience sample of cases through amplification and sequencing of the HAV VP1-P2B junction region. Virus isolates from 1,190 (22%) cases were genotyped; 69% were subgenotype IB, 30% were subgenotype IA, and 1% were subgenotype IIIA. Subgenotype IB was more common among cases reporting recent drug use or homelessness, whereas IA was more common among those reporting recent international travel and among men who have sex with men. Genotype IB infection was associated with a more than 4-fold greater odds of death compared to IA infection. A network analysis revealed 11 genomic clusters of 10 or more cases, with distinct temporal and spatial distributions. Case reports in 2023 decreased to below pre-2018 numbers, likely due to high population immunity following natural infection and extensive vaccination activities in the highest risk groups.

The effect of preexisting neutralizing antibodies (NAb) on SARS-CoV-2 shedding in postvaccination infection (PVI) is not well understood. We characterized viral shedding longitudinally in nasal specimens in relation to baseline (pre/periinfection) serum NAb titers in 125 participants infected with SARS-CoV-2 variants. Among 68 vaccinated participants, we quantified the effect of baseline NAb titers on maximum viral RNA titers and infectivity duration. Baseline NAbs were higher and targeted a broader range of variants in participants with monovalent ancestral booster vaccinations compared with those with a primary vaccine series. In Delta infections, baseline NAb titers targeting Delta or Wuhan-Hu-1 correlated negatively with maximum viral RNA. Per log10 increase in Delta-targeting baseline NAb IC50, maximum viral load was reduced -2.43 (95% CI: -3.76, -1.11) log10 nucleocapsid copies, and infectious viral shedding was reduced -2.79 (95% CI: -4.99, -0.60) days. Conversely, in Omicron infections (BA.1, BA.2, BA.4, or BA.5), baseline NAb titers against Omicron lineages or Wuhan-Hu-1 did not predict viral outcomes. Our results provide robust estimates of the effect of baseline NAbs on the magnitude and duration of nasal viral replication after PVI (albeit with an unclear effect on transmission) and show how immune escape variants efficiently evade these modulating effects.

This case series investigates trends in time from onset of alpha-gal syndrome to diagnosis among patients with disease onset from 1977 to 2019. | eng

Conducting persistence studies of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on environmental surfaces may require a biosafety level 3 (BSL-3) laboratory. We aimed to compare the environmental persistence of BSL-2 level human coronaviruses (229E, NL63, and OC43) and bovine coronavirus (BoCoV) with three SARS-CoV-2 variants (WA-1, Delta, and Omicron). OC43 (1.8 TCID(50)/mL) and BoCoV (1.0 TCID(50)/mL) had lower detection thresholds in cell culture assays compared to 229E (150 TCID(50)/mL) and NL63 (2,670 TCID(50)/mL) and were used for persistence tests at room temperature. Viable OC43 became undetectable (>5.2log(10)) after 48 hours on stainless steel and plastic coupons but exhibited extended persistence up to 72 hours on touchscreen glass coupons. In contrast, BoCoV remained viable for up to 120 hours with <1.8 log(10) infectivity loss. Both OC43 and BoCoV showed a reduction of >5 log(10) on vinyl coupons after 48 hours. On stainless steel coupons, the viability of all three SARS-CoV-2 variants became undetectable (>2.3 log(10) reduction) after 48 hours, with minor differences in reduction levels at 24 hours, whereas on touchscreen glass coupons, the viable virus could be detected for up to 48 hours for WA-1 and Omicron and 72 hours for the Delta variant. Regardless of coupon or virus type, viral RNA titers increased <4.5 Ct values after 120 hours. Our data demonstrate distinct persistence characteristics between BoCoV and OC43, with neither fully mimicking SARS-CoV-2 variants. This variability along with the impact of surface types on viral persistence underscores the need for caution when using these viruses as surrogates for SARS-CoV-2.IMPORTANCEIn this study, we evaluated three human seasonal coronaviruses (OC43, NL63, and 229E) and one bovine coronavirus (BoCoV) as potential surrogate viruses for SARS-CoV-2. Our data suggest that among the four surrogate viruses tested, OC43 and BoCoV were the most promising candidates due to their assay sensitivity, ease of handling, and high genetic similarity to SARS-CoV-2. However, neither BoCoV nor OC43 fully mimicked the environmental persistence characteristics of SARS-CoV-2 variants highlighting the potential limitations of using surrogate viruses.

Emergency department (ED) visits during influenza seasons represent a critical yet less examined indicator of the acute burden of influenza. This study investigates the burden of influenza-associated ED visits in six U.S. cities during influenza seasons from 2005-06 to 2016-17. Using a time-series design, we estimated associations between daily ED visits and weekly influenza activity data from the Influenza Hospitalization Surveillance Network (FluSurv-NET). A counterfactual approach was then used to calculate attributable expected ED. Highest influenza-associated rates were observed among the youngest (0-4 years) and oldest (65+ years) age groups. Combining estimates across seasons, the influenza-associated ED visit rate for respiratory diseases was almost six times larger compared to the subset of ED visits that resulted in hospitalization: 364 per 100,000 population (95% CI: 294-435) for total ED visits versus 58 per 100,000 population (95% CI: 45-71) for hospitalization. This difference was particularly large for the 0-4 year age group: 911 per 100,000 population (95% CI: 558-1,263) for total ED visits versus 43 per 100,000 population (95% CI: 15-71) for hospitalization. This study highlights the substantial burden of influenza on emergency healthcare services and the importance of integrating such data into public health planning and influenza management strategies.

This study examines respiratory syncytial virus (RSV) genomic surveillance results from 2 large US networks after the introduction of RSV vaccines. | eng

Relapsing fever Borrelia (RFB) employs antigenic variation to alter its surface protein structure in response to host immune pressure. This process occurs by the single translocation of archived variable major protein (Vmp) pseudogenes into a vmp expression locus. Borrelia miyamotoi, phylogenetically grouped with RFB, has the genetic makeup for antigenic variation, but it has not been determined whether B. miyamotoi can create new variant serotypes in vivo. We inoculated mice with a non-clonal parental B. miyamotoi CT13-2396 strain with a known Vmp majority serotype with spirochete isolation at various days post-infection. The vmp that determined the reisolated variant serotype was identified by PCR of the expression locus followed by DNA sequencing of the amplified product. For each mouse reisolate, new variants replaced the parent majority serotype. Moreover, some mice produced additional variant reisolates days apart, indicative of the presentation seen in relapsing fever infections. Infection of mice with a clonal population resulted in the elimination of the inoculated serotype and isolation of new variants. Mouse serum obtained following infection revealed IgM antibodies reactive to the parent Vmp serotype, suggesting that the immune response eliminated or greatly reduced the majority population. These results demonstrated that B. miyamotoi reisolated from infected mice exhibited serotype populations differing from the inoculated strain, indicating the spirochetes underwent antigenic variation to evade the host's immune response. However, whether the observed variation occurred by way of outgrowth of minority populations or by translocation of archived pseudogenes to the expression locus creating new variants awaits further study.

Krabbe disease (KD), which affects 0.3-2.6 per 100 000 live births, is an autosomal recessive lysosomal disorder caused by variants in the GALC gene that reduce galactosylceramidase (GALC) activity, leading to psychosine accumulation, cerebral white matter degeneration, and peripheral neuropathy. The most common form, infantile KD (IKD), has onset by 12 months with irritability, feeding difficulty, neurologic regression, and, when untreated, death in early childhood. Hematopoietic stem cell transplantation (HSCT) for IKD approximately 1 month after birth can improve long-term survival but has about a 10% risk of mortality within 100 days, and affected individuals can still have significant functional impairment. Newborn screening for KD is based on low GALC levels in dried-blood spots. Second-tier testing to assess whether an elevated psychosine concentration is present in the same dried-blood spot improves the specificity of screening for IKD. Without newborn screening, diagnosis of IKD is generally made after significant clinical symptoms develop, past when HSCT can be effective. The benefit of newborn detection of later-onset phenotypes of KD is uncertain. In 2024, the US Secretary of Health and Human Services added IKD to the Recommended Uniform Screening Panel after a recommendation by the Advisory Committee on Heritable Disorders in Newborns and Children. For IKD newborn screening to be as effective as possible, it is important to have systems in place to support families in making challenging decisions soon after diagnosis about whether to pursue HSCT and to ensure rapid access to HSCT if chosen.

We used clinical metagenomic next-generation sequencing of cerebrospinal fluid to investigate bunyavirus infections in 2 immunocompromised patients in the United States who had fatal meningoencephalitis. Potosi virus has been isolated from mosquito vectors and Lone Star virus from tick vectors. These findings highlight the power of metagenomic next-generation sequencing in broad-based, agnostic detection of emerging viral infections that test negative using conventional targeted diagnostic methods.

Spotted fever group rickettsioses (SFGR) pose a global threat as emerging zoonotic infectious diseases; however, timely and cost-effective diagnostic tools are currently limited. We used data from 449 patients presenting to 2 hospitals in northern Tanzania between 2007 and 2008, of which 71 (15.8%) met criteria for acute SFGR based on ≥4-fold rise in antibody titers between acute and convalescent serum samples. We fit random forest classifiers incorporating clinical and demographic data from hospitalized febrile participants as well as Earth observation hydrometeorological predictors from the Kilimanjaro Region. In cross-validation, a prediction model with 10 clinical predictors achieved an area under the receiver operating characteristic curve of 0.65 (95% confidence interval, .48-.82). A combined prediction model with clinical, hydrometeorological, and environmental predictors (20 predictors total) did not significantly improve model performance. Novel strategies are needed to improve the diagnosis of acute SFGR, including the identification of diagnostic biomarkers that could enhance clinical prediction models.

PURPOSE: Type 1 hereditary hemochromatosis (HH) can result in iron overload and liver disease if not detected and treated early. Most cases are found among people homozygous for HFE p.Cys282Tyr variants. Compound heterozygosity with the HFE p.His63Asp variant is associated with disease to a lesser degree. We sought to examine the association of HFE variation with HH-related phenotypes and assess the prevalence of testing and diagnosis of HH using All of Us data. METHODS: We used data from 133,978 participants with genetic information linked to medical records. For different HFE genotypes, we examined the prevalence of HH diagnosis codes and related biochemical and clinical phenotypes. RESULTS: Among participants who were p.Cys282Tyr homozygotes, the prevalence of HH diagnosis codes was 22.6% among males and 15.6% among females. Serum transferrin-iron saturation measures were available only for 31.4% of males and 21.1% of females who were p.Cys282Tyr homozygotes. Liver disease, including cirrhosis or hepatocellular carcinoma, was present more among males who were p.Cys282Tyr homozygotes compared with males with no p.Cys282Tyr or p.His63Asp variants (15.5% vs 8.5%, P = .0001). Of the 71 participants who were p.Cys282Tyr homozygotes with indication of liver disease, 32 (45.1%) did not have a serum transferrin-iron saturation measure, and 37 (52.1%) did not have diagnosis codes for HH. CONCLUSION: Limited serum transferrin-iron saturation measures or HH diagnosis codes among p.Cys282Tyr homozygotes, even those with liver disease, suggests potential undertesting and underdiagnosis of type 1 HH in clinical practice and a need for improved awareness, education, and testing around HH.

We describe the epidemiology of invasive group B streptococcal (GBS) disease among non-pregnant Alaska adults using statewide surveillance data. During 2004-2023, 880 cases of invasive GBS disease were reported for an age-adjusted annual incidence of 9.1 (95% CI, 8.5-9.7) cases per 100,000 adults. Incidence increased 1.9-fold (95% CI, 1.6-2.2) between 2004-2013 and 2014-2023. Adults aged ≥65 years had a 4.4-fold higher risk of invasive disease compared to younger adults, and 47% of adults with invasive GBS had diabetes. Healthcare providers should be aware of populations at increased risk, potentially allowing for more prompt treatment.

BACKGROUND: Noroviruses are the leading cause of acute gastroenteritis worldwide with GII.4 Sydney viruses responsible for the majority of infections until 2023. METHODS: To study the evolutionary dynamics of GII.4 noroviruses in the US (2011-2023), we sequenced and analyzed 406 VP1 and 335 RdRp sequences submitted to CaliciNet. RESULTS: Time-scale analysis showed the average evolutionary rate of GII.4 strains was 5.56 x 10-3 substitutions/site/year and the emergence of a new cluster within GII.4 Sydney every 4 years starting with GII.4 Sydney[P31] from 2011-2015 followed by GII.4 Sydney[P16] from 2016-2020, and the most recent GII.4 Sydney[P16]-2020 from 2021-to date. Since 2017, based on amino acids in VP1, we observed the emergence of three novel GII.4 clusters (GII.4 San Francisco, GII.4 Allegany and GII.4 Wichita). GII.4 Sydney was identified with 4 P-types (P4, P12, P16, and P31). GII.4 San Francisco and GII.4 Allegany had a P31 RdRp, whereas GII.4 Wichita strains had P4. GII.4 Allegany and GII.4 Wichita exhibited major amino acid substitutions in epitopes A-E, G, and H, while GII.4 San Francisco viruses have an alanine insertion in epitope A. Both GII.4 Allegany and GII.4 Wichita VLPs bound porcine gastric mucin at a similar level as GII.4 New Orleans and GII.4 Sydney. However, blocking of binding to VLPs by human serum pools demonstrated their antigenicity was significantly different. CONCLUSION: We identified three new emerging GII.4 noroviruses co-circulating with GII.4 Sydney. Early detection of new strains will aid in tracking their spread and assessing their pandemic potential.

BACKGROUND: The prevalence and risk factors for ongoing symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [SCV2]) or influenza infection are not well characterized. We conducted a prospective cohort study of households wherein ≥1 individual was infected with SCV2 or influenza to evaluate prevalence of and factors associated with ongoing symptoms at 90 days. METHODS: Index cases and their household contacts provided baseline health and sociodemographic information and collected daily respiratory specimens for 10 days following enrollment. Participants completed a follow-up survey 90 days after enrollment to characterize ongoing symptoms. RESULTS: We analyzed 1967 participants enrolled between December 2021 and May 2023. The risk of ongoing symptoms did not differ by infection status in SCV2 (SCV2-positive: 15.6%; SCV2-negative: 13.9%; odds ratio [OR]: 1.14; 95% CI: .7-1.69) or influenza (influenza-positive: 8.8%; influenza-negative: 10.0%; OR: .87; 95% CI: .45-1.72) households. However, among study participants with a documented infection, SCV2-positive participants had nearly twice the odds of ongoing symptoms as influenza-positive participants (OR: 1.92; 95% CI: 1.27-2.97). CONCLUSIONS: These results suggest that SCV2 households have a significantly higher prevalence of ongoing symptoms compared with influenza households (OR: 1.78; 95% CI: 1.28-2.47). Among participants with SCV2 infection, underlying conditions (adjusted OR [aOR]: 2.65; 95% CI: 1.80-3.90) and coronavirus disease 2019 (COVID-19)-like symptoms (aOR: 2.92; 95% CI: 1.15-7.43) during acute infection increased odds of ongoing symptoms at 90 days, whereas hybrid immunity reduced the odds of ongoing symptoms (aOR: 0.44; 95% CI: .22-.90).

We report a case of mpox in a patient with a signal transducer and activator of transcription 1 gain-of-function mutation. Despite initial improvement with intravenous immune globulin and tecovirimat, severe symptoms developed and the patient died. This underscores the need for immune system optimization and effective virucidal treatments for mpox.

Human norovirus causes more than 700 million illnesses annually. Extensive genetic diversity and a paucity of information on conserved neutralizing epitopes pose major obstacles to the design of broadly protective norovirus immunogens. Here, we used high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS)-driven proteomics to quantitatively characterize the circulating serum IgG repertoire before and after immunization with an experimental monovalent norovirus GII.4 VP1 capsid-encoding adenoviral vaccine. Two participants were specifically selected on the basis of the breadth of serum neutralization responses either across GII.4 variants (participant A) or across GII genotypes (participant B). In participant A, vaccination back-boosted highly abundant serum antibody clonotypes targeting epitopes conserved among rapidly evolving GII.4 variants spanning from a strain identified in 1987 to a strain identified in 2019. In participant B, we identified a recall response consisting of broadly neutralizing monoclonal antibodies with remarkable cross-GII ligand-binding blockade (blocking ≥ seven GII genotypes) and virus neutralization breadth. The cocrystal structure of one of these antibodies, VX22, in complex with the VP1 capsid protruding (P) domain revealed a highly conserved epitope (residues 479 to 484 and 509 to 513) within two lateral loops of the P1 subdomain. Antibody evolutionary trajectory analysis further revealed that VX22 had originally evolved from an early heterologous infection, likely by a GII.12 strain. Together, our study demonstrates that norovirus human monoclonal antibodies with broad GII.4 potency and cross-GII breadth can be boosted in serum after immunization with an adenoviral vector-based vaccine, findings that may guide the design of immunogens for broadly protective norovirus vaccines.

BACKGROUND: Clusters of rapid HIV transmission indicate larger underlying networks that are not effectively reached by HIV prevention, testing, and care services. Starting in 2018, the Centers for Disease Control and Prevention (CDC) funded 59 U.S. health departments (HDs) to detect and respond to HIV clusters; HDs began reporting clusters to CDC in January 2020. METHODS: For clusters reported to CDC, we described cluster characteristics at detection, including detection method; size; HIV transmission category, defined as that of >50% of cluster members; and HD investigation and response activities. RESULTS: During 2020-2022, 45 HDs reported 322 HIV clusters, with most detected by molecular analysis of HIV sequences (75%). Most were detected in the South (46%) and three-quarters were predominant sexual transmission. Median cluster size at detection for molecular clusters was 10 persons (interquartile range 7-18). Among 205 clusters with follow-up data, investigation and response activities were conducted for 95%, including direct outreach to persons in clusters for partner services (64%), medical chart reviews (42%), and focused testing events (13%). Limited data on named partners tested showed that 11% received new HIV diagnoses. CONCLUSIONS: HD HIV cluster detection activities detected many clusters. Response activities were tailored for different clusters and intervened in networks with rapid transmission and high undiagnosed infection, as indicated by high positivity among partners. Cluster detection and response is an important tool to identify and address gaps in HIV prevention, testing, and care that facilitate rapid transmission.

BACKGROUND: Chronic respiratory diseases (CRDs) are the third leading cause of death worldwide. Data of the associations between specific volatile organic compounds (VOCs), a major component of air pollution and tobacco smoke, and subsequent CRD mortality in the general population are scarce. METHODS: In a case-cohort analysis within the population-based Golestan cohort study (n = 50045, aged 40-75 years, 58% women, enrollment: 2004-2008, northeastern Iran), we included all participants who died from CRD during follow-up through 2018 (n = 242) as cases and stratified them into 16 strata defined by age, sex, residence, and tobacco smoking. Subcohort participants (n = 610) were randomly selected from all eligible cohort participants in each stratum, and sampling fractions were calculated. Baseline urine samples were used to measure 20 VOCs using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. After excluding participants with previous history of CRDs, we used stratified Cox regression models weighted by the inverse sampling fractions (i.e. inverse probability weighting) adjusted for potential confounders, including urinary cotinine and pack-years of smoking, to calculate hazard ratios (HR) for the associations between biomarker tertiles and CRD mortality. RESULTS: Data from 545 non-case, sub-cohort participants and 149 cases (69.1% chronic obstructive pulmonary disease, 13.4% asthma, 17.5% other CRDs) were assessed in this study. During a follow-up of 10.5 years, associations [2nd and 3rd vs. 1st tertiles, HR (95% confidence interval), p for trend] were observed between metabolites of acrolein [1.56 (0.64,3.79), 3.53 (1.53,8.16), 0.002] and styrene/ethylbenzene [1.17 (0.53,2.60), 3.24 (1.37,7.66), 0.005] and CRD mortality, which persisted after excluding the first four years of follow-up. CONCLUSION: Our findings support prior research suggesting respiratory toxicity of VOCs. Further investigation and monitoring of these compounds, especially acrolein and styrene/ethylbenzene, as CRD risk factors, are recommended.

Foodborne illness is a continuous public health risk. The recognition of signals indicating a cluster of foodborne illness is key to the detection, mitigation, and prevention of foodborne adverse event incidents and outbreaks. With increased internet availability and access, novel data streams (NDSs) for foodborne illness reports initiated by users outside of the traditional public health framework have emerged. These include, but are not limited to, social media websites, web-based product reviews posted to retailer websites, and private companies that host public-generated notices of foodborne illnesses. Information gathered by these platforms can help identify early signals of foodborne illness clusters or help inform ongoing public health investigations. Here we present an overview of NDSs and 3 investigations of foodborne illness incidents by the US Food and Drug Administration that included the use of NDSs at various stages. Each example demonstrates how these data were collected, integrated into traditional data sources, and used to inform the investigation. NDSs present a unique opportunity for public health agencies to identify clusters that may not have been identified otherwise, due to new or unique etiologies, as shown in the 3 examples. Clusters may also be identified earlier than they would have been through traditional sources. NDSs can further provide investigators supplemental information that may help confirm or rule out a source of illness. However, data collected from NDSs are often incomplete and lack critical details for investigators, such as product information (eg, lot numbers), clinical or medical details (eg, laboratory results of affected individuals), and contact information for report follow-up. In the future, public health agencies may wish to standardize an approach to maximize the potential of NDSs to catalyze and supplement adverse event investigations. Additionally, the collection of essential data elements by NDS platforms and data-sharing processes with public health agencies may aid in the investigation of foodborne illness clusters and inform subsequent public health and regulatory actions.

BACKGROUND: In Zambia, the true extent of SARS-CoV-2 infections is unknown because initial surveillance focused on patients with symptoms or severe disease. Antenatal sentinel surveillance had not been used to assess infection trends. The ANC COVID-19 surveillance study sought to determine SARS-CoV-2 seroprevalence and COVID-19 vaccine uptake among pregnant women. We provide insight into the study implementation, challenges encountered, best practices, and lessons learned. METHODS: A repeated cross-sectional seroprevalence survey was implemented at 39 health facilities in four districts from September 2021 to September 2022. Pregnant women aged 15-49 years were enrolled at their first antenatal care visits. An electronic questionnaire gathered demographics and other COVID-19 related information from consenting participants. A dried blood sample was collected to detect IgG antibodies using a multiplex bead assay. Seropositive results were categorized as infection, infection and vaccination or infection based on anti-RBD and anti-nucleocapsid test results. Problems and their root causes were identified as they occurred. Practical problem-solving strategies were devised, implemented, and monitored to ensure that goals were accomplished. RESULTS: In the primary analysis, 7% of the 9,221 samples collected from participants were not tested because they were missing. COVID-19 vaccine uptake of 9,111 pregnant women was assessed. Approximately 64% of participants were cumulatively seropositive for SARS-CoV-2 antibodies. Seroprevalence increased from 27.8% in September 2021 to 56.6% in July 2022. We observed an increase in vaccine coverage (0.5-27%) over time. Women aged 40-49 years old, without education and with prior COVID-19 infection were associated with higher vaccine uptake. The Delta variant of COVID-19 and the reallocation of health facilities between two partners delayed surveillance activities and increased the cost of implementation (e.g., the purchase of additional calibration and validation kits and DBS cards). Protocol deviations were attributed to the lack of experience in conducting research but, the district RAs repeatedly trained health facility staff to enhance their research knowledge. CONCLUSIONS: Incorporating SARS-CoV-2 surveillance into routine antenatal care is feasible and potentially sustainable when existing health system infrastructure, human resources, and surveillance systems are leveraged. Yet, careful planning is needed to anticipate implementation challenges and ensure high-quality data collection.

BACKGROUND: International Classification of Disease (ICD) codes can accurately identify patients with certain congenital heart defects (CHDs). In ICD-defined CHD data sets, the code for secundum atrial septal defect (ASD) is the most common, but it has a low positive predictive value for CHD, potentially resulting in the drawing of erroneous conclusions from such data sets. Methods with reduced false positive rates for CHD among individuals captured with the ASD ICD code are needed for public health surveillance. METHODS: We propose a two-level classification system, which includes a CHD and an ASD classification model, to categorize cases with an ASD ICD code into three groups: ASD, other CHD, or no CHD (including patent foramen ovale). In the proposed approach, a machine learning model that leverages structured data is combined with a text classification system. We compare performances for three text classification strategies: support vector machines (SVMs) using text-based features, a robustly optimized Transformer-based model (RoBERTa), and a scalable tree boosting system using non-text-based features (XGBoost). RESULTS: Using SVM for both CHD and ASD resulted in the best performance for the ASD and no CHD group, achieving F(1) scores of 0.53 (±0.05) and 0.78 (±0.02), respectively. XGBoost for CHD and SVM for ASD classification performed best for the other CHD group (F(1) score: 0.39 [±0.03]). CONCLUSIONS: This study demonstrates that it is feasible to use patients' clinical notes and machine learning to perform more fine-grained classification compared to ICD codes, particularly with higher PPV for CHD. The proposed approach can improve CHD surveillance.

BACKGROUND: There have been several recent reports of Clostridioides difficile infection (CDI) due to isolates with reduced fidaxomicin susceptibility (minimum inhibitory concentration [MIC] ≥ 2 µg/mL). However, the clinical implications are uncertain because fidaxomicin achieves high concentrations in the intestinal tract. METHODS: In an acute care hospital, we conducted a 3-year cohort study of patients with CDI to determine the frequency of infection with isolates with reduced fidaxomicin susceptibility and the impact on response to fidaxomicin treatment. Stool specimens were cultured for C. difficile, and susceptibility testing was performed using agar dilution. Whole-genome sequencing was used to identify mutations associated with reduced fidaxomicin susceptibility and to determine relatedness of isolates. For genomically related susceptible and reduced susceptibility isolates from the same patient, we compared rates of growth, sporulation, and toxin production. RESULTS: Of 108 fidaxomicin-treated patients, 6 (5.6%) were infected with isolates that possessed reduced fidaxomicin susceptibility (MICs 8-32 µg/mL), including 3 with initially susceptible isolates followed by clinical failure with subsequent recovery of genomically related isolates with reduced susceptibility. Isolates with reduced fidaxomicin susceptibility harbored mutations in RNA polymerase associated with reduced susceptibility and exhibited reduced toxin production, and 20% to 40% of isolates tested had reduced growth and/or sporulation in comparison with susceptible isolates. Three patients were infected with genomically indistinguishable ribotype 097 isolates with reduced fidaxomicin susceptibility. CONCLUSIONS: Our findings highlight the potential for the emergence on therapy of clinically relevant reduced fidaxomicin susceptibility in C. difficile and its spread via transmission to other patients.

BACKGROUND: Mobile health (mHealth) apps provide easy and quick access for end users to monitor their health-related activities. Features such as medication reminders help end users adhere to their medication schedules and automatically record these actions, thereby helping manage their overall health. Due to insufficient mHealth tools tailored for HIV preventive care in young men who have sex with men (MSM), our study evaluated the usability of the mChoice app, a tool designed to enhance preexposure prophylaxis (PrEP) adherence and promote sexual health (eg, encouraging the use of condoms and being aware of the partner's HIV status and PrEP use). OBJECTIVE: This study aimed to apply systematic usability evaluations to test the mChoice app and to refine the visualizations to better capture and display patient-reported health information. METHODS: Usability testing involved heuristic evaluations conducted with 5 experts in informatics and user testing with 20 young MSM who were taking or were eligible to take PrEP. RESULTS: End users demonstrated satisfaction with the appearance of the mChoice app, reporting that the app has an intuitive interface to track PrEP adherence. However, participants highlighted areas needing improvement, including chart titles and the inclusion of "undo" and "edit" buttons to improve user control when recording PrEP use. CONCLUSIONS: Usability evaluations involving heuristic experts and end users provided valuable insights into the mChoice app's design. Areas for improvement were identified, such as enhancing chart readability and providing additional user controls. These findings will guide iterative refinements, ensuring that future versions of the app better address the needs of its target audience and effectively support HIV prevention.