BACKGROUND: Experimental studies have shown associations between gestational phthalate exposure and behavioral problems among offspring; however, epidemiological evidence is still mixed. This study aims to investigate whether gestational phthalate exposure is associated with behavioral problems in preschool-aged children. METHODS: Participants include 178 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a cohort with high familial likelihood of autism spectrum disorder (ASD). We quantified 14 phthalate metabolites in multiple maternal urine samples collected during the 2nd and 3rd trimesters. Preschool behavior problems were assessed using the Child Behavioral Checklist (CBCL), a standardized instrument for evaluating behavior problems of children aged 1.5-5 years. To examine associations of CBCL scores with both individual phthalate biomarker concentrations and their mixture, we used negative binomial regression and weighted quantile sum regression. RESULTS: Overall, maternal phthalate biomarker concentrations were not associated with child behavior problems. Monoisobutyl phthalate (MiBP) concentrations were inversely associated with child anxious/depressed symptoms and somatic complaints. Mono-hydroxy-isobutyl phthalate (MHiBP) and monobenzyl phthalate (MBzP) were also inversely associated with somatic complaints. When assessing trimester-specific associations, more behavior problems were associated with the 2nd trimester biomarker concentrations: mono(3-carboxypropyl) phthalate (MCPP) and monocarboxyisononyl phthalate (MCNP) were positively associated with somatic complaints. All associations became non-significant after false discovery rate correction. No association between a mixture of phthalates and CBCL scores was found. CONCLUSIONS: Our study observed no clear evidence of gestational phthalate exposure on child behavior problems. However, our findings based on the biomonitoring assessment of multiple samples per participant could improve our understanding of gestational phthalate exposure in association with behavior problems in preschool-aged children.

Ebola disease (EBOD) in humans is a severe disease caused by at least four related viruses in the genus Orthoebolavirus, most often by the eponymous Ebola virus. Due to human-to-human transmission and incomplete success in treating cases despite promising therapeutic development, EBOD is a high priority in public health research. Yet despite almost 50 years since EBOD was first described, the sources of these viruses remain undefined and much remains to be understood about the disease epidemiology and virus emergence and spread. One important approach to improve our understanding is detection of antibodies that can reveal past human infections. However, serosurveys routinely describe seroprevalences that imply infection rates much higher than those clinically observed. Proposed hypotheses to explain this difference include existence of common but less pathogenic strains or relatives of these viruses, misidentification of EBOD as something else, and a higher proportion of subclinical infections than currently appreciated. The work presented here maps B-cell epitopes in the spike protein of Ebola virus and describes a single epitope that is cross-reactive with an antigen seemingly unrelated to orthoebolaviruses. Antibodies against this epitope appear to explain most of the unexpected reactivity towards the spike, arguing against common but unidentified infections in the population. Importantly, antibodies of cross-reactive donors from within and outside the known EBOD geographic range bound the same epitope. In light of this finding, it is plausible that epitope mapping enables broadly applicable specificity improvements in the field of serology.

Background: In the United States (U.S.), hantavirus pulmonary syndrome (HPS) and non-HPS hantavirus infection are nationally notifiable diseases. Criteria for identifying human cases are based on clinical symptoms (HPS or non-HPS) and acute diagnostic results (IgM+, rising IgG+ titers, RT-PCR+, or immunohistochemistry (IHC)+). Here we provide an overview of diagnostic testing and summarize human Hantavirus disease occurrence and genotype distribution in the U.S. from 2008 to 2020. Methods: Epidemiological data from the national hantavirus registry was merged with laboratory diagnostic testing results performed at the CDC. Residual hantavirus-positive specimens were sequenced, and the available epidemiological and genetic data sets were linked to conduct a genomic epidemiological study of hantavirus disease in the U.S. Findings: From 1993 to 2020, 833 human hantavirus cases have been identified, and from 2008 to 2020, 335 human cases have occurred. Among New World (NW) hantavirus cases detected at the CDC diagnostic laboratory (representing 29.2% of total cases), most (85.0%) were detected during acute disease, however, some convalescent cases were detected in states not traditionally associated with hantavirus infections (Connecticut, Missouri, New Jersey, Pennsylvania, Tennessee, and Vermont). From 1993 to 2020, 94.9% (745/785) of U.S. hantaviruses cases were detected west of the Mississippi with 45.7% (359/785) in the Four Corners region of the U.S. From 2008 to 2020, 67.7% of NW hantavirus cases were detected between the months of March and August. Sequencing of RT-PCR-positive cases demonstrates a geographic separation of Orthohantavirus sinnombreense species [Sin Nombre virus (SNV), New York virus, and Monongahela virus]; however, there is a large gap in viral sequence data from the Northwestern and Central U.S. Finally, these data indicate that commercial IgM assays are not concordant with CDC-developed assays, and that “concordant positive” (i.e., commercial IgM+ and CDC IgM+ results) specimens exhibit clinical characteristics of hantavirus disease. Interpretation: Hantaviral disease is broadly distributed in the contiguous U.S, viral variants are localised to specific geographic regions, and hantaviral disease infrequently detected in most Southeastern states. Discordant results between two diagnostic detection methods highlight the need for an improved standardised testing plan in the U.S. Hantavirus surveillance and detection will continue to improve with clearly defined, systematic reporting methods, as well as explicit guidelines for clinical characterization and diagnostic criteria. Funding: This work was funded by core funds provided to the Viral Special Pathogens Branch at CDC. © 2024

BACKGROUND: U.S. construction workers experience high rates of injury that can lead to chronic pain. This pilot study examined nonpharmacological (without medication prescribed by healthcare provider) and pharmacological (e.g., prescription opioids) pain management approaches used by construction workers. METHODS: A convenience sample of U.S. construction workers was surveyed, in partnership with the U.S. National Institute for Occupational Safety and Health (NIOSH) Construction Sector Program. Differences in familiarity and use of nonpharmacological and pharmacological pain management approaches, by demographics, were assessed using logistic regression models. A boosted regression tree model examined the most influential factors related to pharmacological pain management use, and potential reductions in use were counterfactually modeled. RESULTS: Of 166 (85%) of 195 participants reporting pain/discomfort in the last year, 72% reported using pharmacological pain management approaches, including 19% using opioids. There were significant differences in familiarity with nonpharmacological approaches by gender, education, work experience, and job title. Among 37 factors that predicted using pharmacological and non-pharmacological pain management approaches, training on the risks of opioids, job benefits for unpaid leave and paid disability, and familiarity with music therapy, meditation or mindful breathing, and body scans were among the most important predictors of potentially reducing use of pharmacological approaches. Providing these nonpharmacological approaches to workers could result in an estimated 23% (95% CI: 16%-30%) reduction in pharmacological pain management approaches. CONCLUSION: This pilot study suggests specific factors related to training, job benefits, and worker familiarity with nonpharmacological pain management approaches influence use of these approaches.

BACKGROUND: On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this outbreak was 1.25. We described persons who were exposed to the virus, became infected, and they led to the infection of an unusually high number of cases during the outbreak. METHODS: In this descriptive cross-sectional study, we defined a super-spreader person (SSP) as any person with real-time polymerase chain reaction (RT-PCR) confirmed SVD linked to the infection of ≥ 13 other persons (10-fold the outbreak R). We reviewed illness narratives for SSPs collected through interviews. Whole-genome sequencing was used to support epidemiologic linkages between cases. RESULTS: Two SSPs (Patient A, a 33-year-old male, and Patient B, a 26-year-old male) were identified, and linked to the infection of one probable and 50 confirmed secondary cases. Both SSPs lived in the same parish and were likely infected by a single ill healthcare worker in early October while receiving healthcare. Both sought treatment at multiple health facilities, but neither was ever isolated at an Ebola Treatment Unit (ETU). In total, 18 secondary cases (17 confirmed, one probable), including three deaths (17%), were linked to Patient A; 33 secondary cases (all confirmed), including 14 (42%) deaths, were linked to Patient B. Secondary cases linked to Patient A included family members, neighbours, and contacts at health facilities, including healthcare workers. Those linked to Patient B included healthcare workers, friends, and family members who interacted with him throughout his illness, prayed over him while he was nearing death, or exhumed his body. Intensive community engagement and awareness-building were initiated based on narratives collected about patients A and B; 49 (96%) of the secondary cases were isolated in an ETU, a median of three days after onset. Only nine tertiary cases were linked to the 51 secondary cases. Sequencing suggested plausible direct transmission from the SSPs to 37 of 39 secondary cases with sequence data. CONCLUSION: Extended time in the community while ill, social interactions, cross-district travel for treatment, and religious practices contributed to SVD super-spreading. Intensive community engagement and awareness may have reduced the number of tertiary infections. Intensive follow-up of contacts of case-patients may help reduce the impact of super-spreading events.

The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 10(10) to 10(12) virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).

BACKGROUND: Early isolation and care for Ebola Disease patients at Ebola Treatment Units (ETU) curb outbreak spread. We evaluated time to ETU entry and associated factors during the 2022 Sudan virus disease (SVD) outbreak in Uganda. METHODS: We included persons with RT-PCR-confirmed SVD with onset September 20-November 30, 2022. We categorized days from symptom onset to ETU entry ('delays') as short (≤2), moderate (3-5), and long (≥6); the latter two were 'delayed isolation'. We categorized symptom onset timing as 'earlier' or 'later,' using October 15 as a cut-off. We assessed demographics, symptom onset timing, and awareness of contact status as predictors for delayed isolation. We explored reasons for early vs late isolation using key informant interviews. RESULTS: Among 118 case-patients, 25 (21%) had short, 43 (36%) moderate, and 50 (43%) long delays. Seventy-five (64%) had symptom onset later in the outbreak. Earlier symptom onset increased risk of delayed isolation [cRR=1∙8, 95%CI (1∙2-2∙8)]. Awareness of contact status and SVD symptoms, and belief that early treatment-seeking was lifesaving facilitated early care-seeking. Patients with long delays reported fear of ETUs and lack of transport as contributors. CONCLUSION: Delayed isolation was common early in the outbreak. Strong contact tracing and community engagement could expedite presentation to ETUs.

Ebola virus disease (Ebola) is a rare but severe illness in humans, with an average case fatality rate of approximately 50%. Two licensed vaccines are currently available against Orthoebolavirus zairense, the virus that causes Ebola: the 1-dose rVSVΔG-ZEBOV-GP (ERVEBO [Merck]) and the 2-dose regimen of Ad26.ZEBOV and MVA-BN-Filo (Zabdeno/Mvabea [Johnson & Johnson]). The Strategic Advisory Group of Experts on Immunization recommends the use of 1-dose ERVEBO during Ebola outbreaks, and in 2021, a global stockpile of ERVEBO was established to ensure equitable, timely, and targeted access to vaccine doses for future Ebola outbreaks. This report describes the use of Ebola vaccines and the role of the stockpile developed and managed by the International Coordinating Group (ICG) on Vaccine Provision during 2021-2023. A total of 145,690 doses have been shipped from the ICG stockpile since 2021. However, because outbreaks since 2021 have been limited and rapidly contained, most doses (139,120; 95%) shipped from the ICG stockpile have been repurposed for preventive vaccination of high-risk groups, compared with 6,570 (5%) used for outbreak response. Repurposing doses for preventive vaccination could be prioritized in the absence of Ebola outbreaks to prevent transmission and maximize the cost-efficiency and benefits of the stockpile.

Over the past 70 years, significant advances have been made in determining the causes of death in populations not served by official medical certification of cause at the time of death using a technique known as Verbal Autopsy (VA). VA involves an interview of the family or caregivers of the deceased after a suitable bereavement interval about the circumstances, signs and symptoms of the deceased in the period leading to death. The VA interview data are then interpreted by physicians or, more recently, computer algorithms, to assign a probable cause of death. VA was originally developed and applied in field research settings. This paper traces the evolution of VA methods with special emphasis on the World Health Organization's (WHO)'s efforts to standardize VA instruments and methods for expanded use in routine health information and vital statistics systems in low- and middle-income countries (LMICs). These advances in VA methods are culminating this year with the release of the 2022 WHO Standard Verbal Autopsy (VA) Toolkit. This paper highlights the many contributions the late Professor Peter Byass made to the current VA standards and methods, most notably, the development of InterVA, the most commonly used automated computer algorithm for interpreting data collected in the WHO standard instruments, and the capacity building in low- and middle-income countries (LMICs) that he promoted. This paper also provides an overview of the methods used to improve the current WHO VA standards, a catalogue of the changes and improvements in the instruments, and a mapping of current applications of the WHO VA standard approach in LMICs. It also provides access to tools and guidance needed for VA implementation in Civil Registration and Vital Statistics Systems at scale.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may adversely affect child behaviors; however, findings of epidemiologic studies are inconsistent. We examined prenatal PFAS exposure in association with child behavioral problems. METHODS: Participants were 177 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a cohort with elevated familial likelihood of autism spectrum disorder (ASD). We quantified nine PFAS in maternal serum (1-3 samples per mother) collected from the 1st to 3rd trimesters of pregnancy. Child behavioral problems were assessed at 3 years of age using the Child Behavior Checklist (CBCL), developed to test for various behavioral problems of children. We examined associations of the CBCL scores with individual PFAS concentrations and with their mixture using negative binomial regression and weighted quantile sum regression models. RESULTS: Higher prenatal perfluorononanoate (PFNA) concentrations were associated with higher scores of externalizing problems [β = 0.16, 95% CI (0.01, 0.32)] and aggressive behavior [β = 0.17 (0.01, 0.32)]. Higher PFNA, perfluorooctane sulfonate (PFOS), and perfluorodecanoate (PFDA) were associated with higher scores of sleep problems [β = 0.34 (0.15, 0.54) for PFNA, β = 0.20 (0.02, 0.37) for PFOS, and β = 0.19 (0.00, 0.37) for PFDA]. No significant associations observed for typically developing children, whereas PFOS, PFNA, and PFDA were associated with several behavioral problems among children diagnosed with ASD or other neurodevelopmental concerns. Exposure to a mixture of PFAS was associated with higher scores of sleep problems and aggressive behavior, mostly contributed by PFNA and PFDA. CONCLUSIONS: Our study showed that prenatal exposure to some PFAS could increase child behavioral problems at 3 years of age. However, our results should be interpreted with caution because we relied on data from a cohort with increased familial likelihood of ASD and thereby had more behavioral problems.

AIMS: Glycoprotein acetyls (GlycA) is a biomarker of systemic inflammation and cardiovascular disease, yet little is known about its role in type 1 diabetes (T1D). We examined the associations among GlycA, central adiposity, insulin resistance, and early kidney injury in youth with T1D. METHODS: Glomerular filtration rate (GFR) and renal plasma flow (RPF) by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by DXA, and estimated insulin sensitivity were assessed in fifty youth with T1D (16±3.0 years, 50% female, HbA(1c) 8.7±1.3%, T1D duration 5.7±2.6 years). Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. RESULTS: GlycA was higher in girls vs. boys (1.05±0.26 vs. 0.84±0.15 mmol/L, p=0.001) and in participants who were overweight/obese vs. normal weight (1.12±0.23 vs. 0.87±0.20 mmol/L, p=0.0004). GlycA correlated positively with estimated intraglomerular pressure (r=0.52, p=0.001), UACR (r=0.53, p<0.0001) and trunk mass (r=0.45, p=0.001), and inversely with estimated insulin sensitivity (r:-0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and HbA(1c). CONCLUSION: GlycA, a biomarker of inflammation, was higher in girls and those of overweight or obese body habitus in T1D. Additionally, GlycA associated with parameters of early kidney dysfunction, central adiposity, and insulin resistance.

We obtained samples from the Department of Defense Serum Repository from soldiers who were stationed at Fort Liberty, North Carolina, between 1991 and 2019 to assess temporal trends in tick-borne rickettsiosis and ehrlichiosis. Serological evidence of infection was common, with nearly 1 in 5 (18.9%) demonstrating antibodies. We observed significant decreases in Rickettsia seroprevalence (adjusted odds ratio [aOR], 0.42 [95% CI, .27-.65], P = .0001) while over the same period Ehrlichia seroprevalence, albeit less common, nearly doubled (aOR, 3.61 [95% CI, 1.10-13.99], P = .048). The increase in Ehrlichia seroprevalence likely reflects increased transmission resulting from the expanding geographic range of the lone star tick.

BACKGROUND: The Democratic Republic of the Congo has had 15 Ebola virus disease (EVD) outbreaks, from 1976 to 2023. On June 1, 2020, the Democratic Republic of the Congo declared an outbreak of EVD in the western Équateur Province (11th outbreak), proximal to the 2018 Tumba and Bikoro outbreak and concurrent with an outbreak in the eastern Nord Kivu Province. In this Article, we assessed whether the 11th outbreak was genetically related to previous or concurrent EVD outbreaks and connected available epidemiological and genetic data to identify sources of possible zoonotic spillover, uncover additional unreported cases of nosocomial transmission, and provide a deeper investigation into the 11th outbreak. METHODS: We analysed epidemiological factors from the 11th EVD outbreak to identify patient characteristics, epidemiological links, and transmission modes to explore virus spread through space, time, and age groups in the Équateur Province, Democratic Republic of the Congo. Trained field investigators and health professionals recorded data on suspected, probable, and confirmed cases, including demographic characteristics, possible exposures, symptom onset and signs and symptoms, and potentially exposed contacts. We used blood samples from individuals who were live suspected cases and oral swabs from individuals who were deceased to diagnose EVD. We applied whole-genome sequencing of 87 available Ebola virus genomes (from 130 individuals with EVD between May 19 and Sept 16, 2020), phylogenetic divergence versus time, and Bayesian reconstruction of phylogenetic trees to calculate viral substitution rates and study viral evolution. We linked the available epidemiological and genetic datasets to conduct a genomic and epidemiological study of the 11th EVD outbreak. FINDINGS: Between May 19 and Sept 16, 2020, 130 EVD (119 confirmed and 11 probable) cases were reported across 13 Équateur Province health zones. The individual identified as the index case reported frequent consumption of bat meat, suggesting the outbreak started due to zoonotic spillover. Sequencing revealed two circulating Ebola virus variants associated with this outbreak-a Mbandaka variant associated with the majority (97%) of cases and a Tumba-like variant with similarity to the ninth EVD outbreak in 2018. The Tumba-like variant exhibited a reduced substitution rate, suggesting transmission from a previous survivor of EVD. INTERPRETATION: Integrating genetic and epidemiological data allowed for investigative fact-checking and verified patient-reported sources of possible zoonotic spillover. These results demonstrate that rapid genetic sequencing combined with epidemiological data can inform responders of the mechanisms of viral spread, uncover novel transmission modes, and provide a deeper understanding of the outbreak, which is ultimately needed for infection prevention and control during outbreaks. FUNDING: WHO and US Centers for Disease Control and Prevention.

Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS).Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model.Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (∼6 hrs) of MUCA.Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants.

Ebola disease outbreaks are major public health events because of human-to-human transmission and high mortality. These outbreaks are most often caused by Ebola virus, but at least three related viruses can also cause the disease. In 2022, Sudan virus re-emerged causing more than 160 confirmed and probable cases. This report describes generation of a recombinant Sudan virus and demonstrates its utility by quantifying antibody cross-reactivity between Ebola and Sudan virus glycoproteins after human infection or vaccination with a licensed Ebola virus vaccine.

Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific symptomatology, inconsistent case reporting, and difficulties with diagnostic testing. We describe a case of acute lymphocytic choriomeningitis virus disease in a person living with HIV in Connecticut, USA, identified by using quantitative reverse transcription PCR.

We identified 2 fatal cases of persons infected with hantavirus in Arizona, USA, 2020; 1 person was co-infected with SARS-CoV-2. Delayed identification of the cause of death led to a public health investigation that lasted ≈9 months after their deaths, which complicated the identification of a vector or exposure.

Ebola virus disease (EVD) caused by Ebola virus species Zaire ebolavirus (EBOV) is a major global health challenge causing sporadic outbreaks with high mortality. The minimum incubation period of EBOV, or the time from infection with the virus to the development of first symptoms, is thought to be 2 days and was initially established during the first EVD investigation in 1976.1 A published observation from the investigation noted that, “in one case of the disease, the only possible source of infection was contact with a probable case 48 hours before the latter developed symptoms”, and this observation was restated in another publication.2, 3 However, concluding that the minimum incubation period for EBOV is 2 days based on these reports is flawed for several reasons. First, the presumed source of the infection was a probable case of EVD and was not laboratory-confirmed; it is therefore uncertain whether the source truly had EVD. Second, since the report describes the contact between the source and the case occurring before the source developed symptoms, this implies asymptomatic transmission, which has been established to not occur with EBOV.4, 5, 6 Finally, the report's description of 48 h refers to the time between the case's contact with the alleged source and the source's onset of symptoms, which is itself not an incubation period.

BACKGROUND: The long-term effects of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) or acute COVID-19 are not well known. Our objective was to determine long-term outcomes. METHODS: Children hospitalized with MIS-C or COVID-19 at 3 US hospitals from March 2020, through February 2021 were followed to assess health through 2 years post-hospitalization using medical records and patient surveys. RESULTS: Medical record abstraction was performed for 183 patients hospitalized with MIS-C, 53 of whom participated in surveys, and 97 patients hospitalized with COVID-19, 35 of whom participated in surveys. Patients with MIS-C were younger (median, 9 vs. 14 years of age for COVID-19 patients; P = 0.004), more frequently male (62% vs. 39%; P < 0.001) and had more cardiac (14% vs. 2%; P = 0.001) and neurologic sequelae (8% vs. 1%; P = 0.023). Children with COVID-19 more often had other comorbidities (59% vs. 19%; P < 0.001). Full mental recovery at the time of survey 2 (median, 16 months post-hospitalization for patients with MIS-C and 20 months for patients with COVID-19) was 85% and 88%, respectively; full physical recovery was 87% and 81%, respectively; and nearly all had resumption of normal activities. Patients with MIS-C reported more frequent headache at 1 month (45% vs. 20%; P = 0.037). Patients with COVID-19 were more likely to report cough at 1 month (37% vs. 17%; P = 0.045). Fatigue persisted >1 year in 15%-20% of patients in both groups. CONCLUSIONS: Approximately 20% of children with MIS-C and COVID-19 continued to have symptoms including fatigue and headache >1 year after hospital discharge. The duration of these findings emphasizes the importance of providers following patients until sequelae have resolved.

The hepatitis B virus (HBV) and hepatitis D virus (HDV) infections cause liver disease, including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HBV infection remains a major global health problem. In 2019, 296 million people were living with chronic hepatitis B and about 5% of them were co-infected with HDV. In vitro cell culture systems are instrumental in the development of therapeutic targets. Cell culture systems contribute to identifying molecular mechanisms for HBV and HDV propagation, finding drug targets for antiviral therapies, and testing antiviral agents. Current HBV therapeutics, such as nucleoside analogs, effectively suppress viral replication but are not curative. Additionally, no effective treatment for HDV infection is currently available. Therefore, there is an urgent need to develop therapies to treat both viral infections. A robust in vitro cell culture system supporting HBV and HDV infections (HBV/HDV) is a critical prerequisite to studying HBV/HDV pathogenesis, the complete life cycle of HBV/HDV infections, and consequently identifying new therapeutics. However, the lack of an efficient cell culture system hampers the development of novel antiviral strategies for HBV/HDV infections. In vitro cell culture models have evolved with significant improvements over several decades. Recently, the development of the HepG2-NTCP sec+ cell line, expressing the sodium taurocholate co-transporting polypeptide receptor (NTCP) and self-assembling co-cultured primary human hepatocytes (SACC-PHHs) has opened new perspectives for a better understanding of HBV and HDV lifecycles and the development of specific antiviral drug targets against HBV/HDV infections. We address various cell culture systems along with different cell lines and how these cell culture systems can be used to provide better tools for HBV and HDV studies.

Background The recent detection of the South Asian malaria vector An. stephensi in Ethiopia and other regions in the Horn of Africa has raised concerns about its potential impact on malaria transmission. We report here findings of survey for this species in eastern Ethiopia using both morphological and molecular methods for species identification.Methods Adult and larval/pupal collections were conducted at ten sites in eastern Ethiopia and Anopheles specimens’ species were determined using standard morphological keys and genetic analysis.Results In total, 2,231 morphologically identified An. stephensi were collected. A molecular approach incorporating both PCR endpoint assay and sequencing of portions of the internal transcribed spacer 2 (ITS2) and cytochrome oxidase I (COI) loci confirmed the identity of the An. stephensi in most cases (119/124 of the morphologically identified An. stephensi confirmed molecularly). Additionally, we observed Aedes aegypti larvae and pupae at many of the An. stephensi larval habitats.Conclusions Our findings show that An. stephensi is widely distributed in eastern Ethiopia and highlight the need for further surveillance in the southern, western and northern parts of the country and throughout the Horn of Africa.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a coronavirus that infects both humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. While some mutations found in camel-derived MERS-CoV strains have been characterized, the majority of natural variation found across MERS-CoV isolates remains unstudied. Here we report on the environmental stability, replication kinetics and pathogenicity of several diverse isolates of MERS-CoV as well as SARS-CoV-2 to serve as a basis of comparison with other stability studies. While most of the MERS-CoV isolates exhibited similar stability and pathogenicity in our experiments, the camel derived isolate, C/KSA/13, exhibited reduced surface stability while another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that while betacoronaviruses may have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the importance of continual, global viral surveillance.

Vaccination against hepatitis B using a dissolving microneedle patch (dMNP) could increase access to the birth dose by reducing expertise needed for vaccine administration, refrigerated storage, and safe disposal of biohazardous sharps waste. In this study, we developed a dMNP to administer hepatitis B surface antigen (HBsAg) adjuvant-free monovalent vaccine (AFV) at doses of 5 µg, 10 µg, and 20 µg, and compared its immunogenicity to vaccination with 10 µg of standard monovalent HBsAg delivered by intramuscular (IM) injection either in an AFV format or as aluminum-adjuvanted vaccine (AAV). Vaccination was performed on a three dose schedule of 0, 3, and 9 weeks in mice and 0, 4, and 24 weeks in rhesus macaques. Vaccination by dMNP induced protective levels of anti-HBs antibody responses (≥10 mIU/ml) in mice and rhesus macaques at all three HBsAg doses studied. HBsAg delivered by dMNP induced higher anti-HBsAg antibody (anti-HBs) responses than the 10 µg IM AFV, but lower responses than 10 µg IM AAV, in mice and rhesus macaques. HBsAg-specific CD4+ and CD8+ T cell responses were detected in all vaccine groups. Furthermore, we analyzed differential gene expression profiles related to each vaccine delivery group and found that tissue stress, T cell receptor signaling, and NFκB signaling pathways were activated in all groups. These results suggest that HBsAg delivered by dMNP, IM AFV, and IM AAV have similar signaling pathways to induce innate and adaptive immune responses. We further demonstrated that dMNP was stable at room temperature (20 °C-25 °C) for 6 months, maintaining 67 ± 6 % HBsAg potency. This study provides evidence that delivery of 10 µg (birth dose) AFV by dMNP induced protective levels of antibody responses in mice and rhesus macaques. The dMNPs developed in this study could be used to improve hepatitis B birth dose vaccination coverage levels in resource limited regions to achieve and maintain hepatitis B elimination.

We appreciate the comments made by Sayed [1] regarding our article [2]. We found that rhesus macaques with experimental hepatitis E virus (HEV) infection demonstrated clinical signs consistent with acute viral hepatitis, viral shedding in feces and serum, and development of antiviral antibody responses that are similar to the natural history of HEV infection in humans [3, 4]. Rhesus macaques are susceptible to infection by HEV genotypes 1–4 and have proved to be a reliable experimental model for studying HEV genotype 1 primary infection and reinfection [2, 5, 6]. As with 2 human volunteer inoculation studies [7, 8], HEV RNA was found in the serum and feces of infected rhesus macaques before the elevation of serum alanine transaminase (ALT) activity [3]. The onset of ALT elevation in the serum and histopathological changes in the liver correlated with immune responses marked by anti-HEV antibody responses and viral clearance from the stool of infected rhesus macaques [3, 5]. Other than nonhuman primates, the experimental studies of HEV infection in pigs, rabbits, and human liver chimeric mice showed no elevation in serum ALT activity [9–11].

On August 1, 2018, the Democratic Republic of the Congo Ministry of Health (DRC MoH) declared the tenth outbreak of Ebola virus disease (Ebola) in DRC, in the North Kivu province in eastern DRC on the border with Uganda, 8 days after another Ebola outbreak was declared over in northwest Équateur province. During mid- to late-July 2018, a cluster of 26 cases of acute hemorrhagic fever, including 20 deaths, was reported in North Kivu province.* Blood specimens from six patients hospitalized in the Mabalako health zone and sent to the Institut National de Recherche Biomédicale (National Biomedical Research Institute) in Kinshasa tested positive for Ebola virus. Genetic sequencing confirmed that the outbreaks in North Kivu and Équateur provinces were unrelated. From North Kivu province, the outbreak spread north to Ituri province, and south to South Kivu province (1). On July 17, 2019, the World Health Organization designated the North Kivu and Ituri outbreak a public health emergency of international concern, based on the geographic spread of the disease to Goma, the capital of North Kivu province, and to Uganda and the challenges to implementing prevention and control measures specific to this region (2). This report describes the outbreak in the North Kivu and Ituri provinces. As of November 17, 2019, a total of 3,296 Ebola cases and 2,196 (67%) deaths were reported, making this the second largest documented outbreak after the 2014-2016 epidemic in West Africa, which resulted in 28,600 cases and 11,325 deaths.(†) Since August 2018, DRC MoH has been collaborating with partners, including the World Health Organization, the United Nations Children's Fund, the United Nations Office for the Coordination of Humanitarian Affairs, the International Organization of Migration, The Alliance for International Medical Action (ALIMA), Médecins Sans Frontières, DRC Red Cross National Society, and CDC, to control the outbreak. Enhanced communication and effective community engagement, timing of interventions during periods of relative stability, and intensive training of local residents to manage response activities with periodic supervision by national and international personnel are needed to end the outbreak.

This article describes 22 cases of breakthrough SARS-CoV-2 infection among over 14,000 fully vaccinated skilled nursing facility residents and staff. The majority of such infections were asymptomatic or were associated with mild symptoms, and there was no intra- facility spread related to these cases. This report suggests that postvaccination breakthrough infections are rare, but also confirms that vaccines do not offer 100% protection even in nonimmunosuppressed hosts, thus underscoring the need for studies of vaccine efficacy in immunosuppressed transplant recipients.

INTRODUCTION: Among individuals with chronic respiratory conditions, transitions between patterns of tobacco product use are not well understood. This study examines how transitions, including quitting altogether, differ over time between those who do and do not have chronic respiratory conditions. METHODS: Data from youth and adult participants of the longitudinal Population Assessment of Tobacco and Health Study (2013-2018) were analyzed. Youth aged 12-17 years were included if they had aged into the adult sample by Wave 4. Stratified polytomous regression models built under a first-order Markov assumption modeled the probability of transitioning between different states/patterns of tobacco product use (exclusive current E-cigarette use, exclusive current combustible tobacco product use, current dual use of combustible products and E-cigarettes, and no current tobacco product use) at each wave. Marginal transition probabilities were computed as a function of ever or past-year diagnosis of a respiratory condition (separately for asthma and a composite variable representing chronic bronchitis, emphysema, and/or chronic obstructive pulmonary disease). Analyses were conducted in 2020-2021. RESULTS: Most individuals, regardless of respiratory condition, maintained the same pattern of tobacco use between waves. Exclusive combustible tobacco product users, including those with or without a respiratory condition, were not likely to become exclusive E-cigarette users or to quit using tobacco entirely. CONCLUSIONS: Although combustible tobacco use negatively impacts the management and prognosis of respiratory illnesses, combustible tobacco users who were recently diagnosed with a chronic respiratory condition were not likely to quit using tobacco. Efforts to encourage and support cessation in this medically vulnerable population should be increased.

Monkeypox (mpox) cases in the 2022 outbreak have primarily occurred among adult gay, bisexual, and other men who have sex with men (MSM); however, other populations have also been affected (1). To date, data on mpox in cisgender women and pregnant persons have been limited. Understanding transmission in these populations is critical for mpox prevention. In addition, among pregnant persons, Monkeypox virus can be transmitted to the fetus during pregnancy or to the neonate through close contact during or after birth (2-5). Adverse pregnancy outcomes, including spontaneous abortion and stillbirth, have been reported in previous mpox outbreaks (3). During May 11-November 7, 2022, CDC and U.S. jurisdictional health departments identified mpox in 769 cisgender women aged ≥15 years, representing 2.7% of all reported mpox cases.(†) Among cases with available data, 44% occurred in cisgender women who were non-Hispanic Black or African American (Black), 25% who were non-Hispanic White (White), and 23% who were Hispanic or Latino (Hispanic). Among cisgender women with available data, 73% reported sexual activity or close intimate contact as the likely route of exposure, with mpox lesions most frequently reported on the legs, arms, and genitals. Twenty-three mpox cases were reported in persons who were pregnant or recently pregnant(§); all identified as cisgender women based on the mpox case report form.(¶) Four pregnant persons required hospitalization for mpox. Eleven pregnant persons received tecovirimat, and no adverse reactions were reported. Continued studies on mpox transmission risks in populations less commonly affected during the outbreak, including cisgender women and pregnant persons, are important to assess and understand the impact of mpox on sexual, reproductive, and overall health.