BACKGROUND: Borealpox virus (BRPV, formerly known as Alaskapox virus) is a zoonotic member of the Orthopoxvirus genus first identified in a person in 2015. In the six patients with infection previously observed BRPV involved mild, self-limiting illness. We report the first fatal BRPV infection in an immunosuppressed patient. METHODS: A man aged 69 years from Alaska's Kenai Peninsula was receiving anti-CD20 therapy for chronic lymphocytic leukemia. He presented to care for a tender, red papule in his right axilla with increasing induration and pain. The patient failed to respond to multiple prescribed antibiotic regimens and was hospitalized 65 days postsymptom onset for progression of presumed infectious cellulitis. BRPV was eventually detected through orthopoxvirus real-time polymerase chain reaction testing of mucosal swabs. He received combination antiviral therapy, including 21 days of intravenous tecovirimat, intravenous vaccinia immunoglobulin, and oral brincidofovir. Serial serology was conducted on specimens obtained posttreatment initiation. FINDINGS: The patient's condition initially improved with plaque recession, reduced erythema, and epithelization around the axillary lesion beginning one-week post-therapy. He later exhibited delayed wound healing, malnutrition, acute renal failure, and respiratory failure. He died 138 days postsymptom onset. Serologic testing revealed no evidence the patient generated a humoral immune response. No secondary cases were detected. CONCLUSION: This report demonstrates that BRPV can cause overwhelming disseminated infection in certain immunocompromised patients. Based on the patient's initial response, early BRPV identification and antiviral therapies might have been beneficial. These therapies, in combination with optimized immune function, should be considered for patients at risk for manifestations of BRPV.

BACKGROUND: Despite widespread HIV testing in sub-Saharan Africa, regular testing among at-risk populations is crucial for effective prevention. However, reports increasingly indicate retesting among people living with HIV (PLHIV), a group that would not require additional testing since they would already have received a confirmed diagnosis. We describe the demographic characteristics of PLHIV retesters in Lesotho, report the average number of HIV tests post-diagnosis among PLHIV, and share motivations for retesting. METHODS: In August 2022, a nationally representative cohort in Lesotho participated in a cell phone survey about their HIV status and testing history. Study participants were recruited from a face-to-face survey conducted in 2020, Lesotho Population Based HIV Impact Assessment survey. RESULTS: Of the 1523 participants called, 1111 participants responded (72.9%) and 266 reported living with HIV. We found 18.8% of people living with HIV (PLHIV) reported retesting at least once for HIV, and 58% of PLHIV who reported retesting were likely or very likely to retest for HIV in the coming year. The main reason PLHIV reported retesting was because a health care worker offered the test (61.7%) followed by self-initiated testing to confirm their status (29.1%). Among male PLHIV who had a history of retesting, 92.0% were very likely or likely to retest, compared to only 30.6% of female PLHIV. CONCLUSION: We found almost a fifth of PLHIV in Lesotho reported a history of retesting for HIV, and 58% of PLHIV were likely or very likely to retest for HIV in the coming year. Educating providers and men living with HIV could reduce retesting among PLHIV.

Background: Free-living amoebas (FLAs) can cause severe and fatal central nervous system infections that are difficult to diagnose. Methods: We present the case of a 74-year-old immunocompetent woman admitted for focal neurological symptoms with enhancing lesions in the right cerebellar hemisphere. A first cerebral biopsy showed granulomatous inflammation, but no microorganisms were identified. After transient clinical improvement, she eventually deteriorated 4 months after initial presentation, with an MRI confirming multiple new masses affecting all cerebral lobes. Results: A second brain biopsy revealed granulomatous and acute inflammation with organisms containing a large central nucleus with prominent karyosome, consistent with FLAs. Immunohistochemical and polymerase chain reaction assays performed at CDC were positive for Acanthamoeba spp, confirming the diagnosis of granulomatous amoebic encephalitis (GAE) caused by Acanthamoeba spp. The patient was treated with combination therapy recommended by CDC, but died a few days later. Upon histopathological rereview, amoebic cysts and trophozoites were identified by histochemical and immunohistochemical methods in the first cerebral biopsy. Conclusion: FLA infections can be challenging to diagnose because of the low incidence, non-specific clinical and radiological presentation, lack of accessible diagnostic tools, and clinicians' unfamiliarity. This case highlights the importance of recognizing FLA as a potential cause of granulomatous encephalitis, even in the absence of risk factors, as early treatment might be associated with favourable outcomes in case reports. When suspected, CDC laboratories offer tests to confirm the diagnosis promptly. | Historique : Les amibes libres peuvent causer des infections du système nerveux central graves et fatales qui sont difficiles à diagnostiquer. Méthodologie : Les auteurs présentent le cas d'une femme immunocompétente de 74 ans hospitalisée à cause de symptômes neurologiques focaux avec lésions rehaussantes dans l'hémisphère cérébelleux droit. Une première biopsie cérébrale a révélé une inflammation granulomateuse, mais aucun microorganisme n'a été décelé. Après une amélioration clinique transitoire, son état s'est détérioré quatre mois après la première consultation, et l'IRM a confirmé de multiples nouvelles masses touchant tous les lobes cérébraux. Résultats : Une deuxième biopsie cérébrale a révélé une inflammation granulomateuse aiguë par des organismes dont les gros noyaux centraux et les caryosomes volumineux étaient évocateurs d'amibes libres. L'immunohistochimie et l'amplification en chaîne par polymérase effectuées aux CDC se sont avérés positives pour Acanthamoeba spp, ce qui a confirmé un diagnostic d'encéphalite amibienne granulomateuse causée par Acanthamoeba spp. La patiente a reçu une polythérapie recommandée par les CDC, mais est malheureusement décédée quelques jours plus tard. À la reprise de l'analyse histopathologique, des kystes amibiens et des trophozoïtes ont été décelés dans la première biopsie cérébrale par des méthodes histochimiques et immunohistochimiques. Conclusion : Les infections par des amibes libres peuvent être difficiles à diagnostiquer en raison de leur faible incidence, de leur présentation clinique et radiologique non spécifique, de l'absence d'outils diagnostiques accessibles et de la méconnaissance des cliniciens. Ce cas renforce l'importance d'inclure les amibes libres dans les causes potentielles d'encéphalite granulomateuse, même en l'absence de facteurs de risque, car un traitement rapide a été associé à des résultats favorables dans certains rapports de cas. Lorsqu'on en soupçonne la présence, les laboratoires des CDC offrent des tests pour confirmer rapidement le diagnostic.

Farmworkers, a group of essential workers, experience a disproportionately high burden of COVID-19 due to their living and working conditions. This project characterized farmworker mobility in and around Yuma County, Arizona, to identify opportunities to improve farmworker access to COVID-19 vaccination. We collected qualitative and geospatial data through a series of in-person and virtual focus group discussions, key informant interviews, and intercept interviews with participatory mapping. Participants included farmworkers, employers, and representatives of local institutions who serve or interact with farmworkers. We identified participants through purposive and referential sampling and grouped people by sociodemographic characteristics for interviews. We used qualitative and geospatial analyses to identify common themes and mobility patterns. The team interviewed 136 people from February 26 to April 2, 2021. Common themes emerged about how farmworkers have little or no access to COVID-19 vaccination unless offered at their workplaces or at locations where they congregate at convenient times. Further, farmworkers described how their demanding work schedules, long commute times, and caretaker commitments make it challenging to access vaccination services. Geospatial analyses identified three geographic areas in Yuma County where farmworkers reported living and working that did not have a COVID-19 vaccine clinic within walking distance. Coordination between local public health authorities and key partners, including employers and trusted representatives from local community-based organizations or the Mexican consulate, to offer vaccination at worksites or other locations where farmworkers congregate can help improve access to COVID-19 vaccines and booster doses for this population.

During October 2021-June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness. Two children were immunocompromised when initially brought for care. Four children tested positive for adenovirus in multiple specimen types, including 2 for whom typing was completed. One adenovirus-positive child had no known underlying conditions, supporting a potential relationship between adenovirus and acute hepatitis in previously healthy children. Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment. Testing for adenovirus in similar cases could elucidate the role of the virus.

Preventing unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, among adolescents is a public health priority. This report presents prevalence estimates for condom and contraceptive use among sexually active U.S. high school students from the 2019 Youth Risk Behavior Survey. Behaviors examined included any condom use, primary contraceptive method use, and condom use with a more effective contraceptive method, all reported at last sexual intercourse. Analyses were limited to sexually active students (i.e., those who had sexual intercourse with one or more persons during the 3 months before the survey). Except for any condom use, students reporting only same-sex sexual contact were excluded from analyses. Weighted prevalence estimates were calculated, and bivariate differences in prevalence were examined by demographic characteristics (sex, race/ethnicity, and grade) and other sexual risk behaviors (age of sexual initiation, previous 3-month and lifetime number of sex partners, and substance use before last sexual intercourse). Nationwide, 27.4% of high school students reported being sexually active (n = 3,226). Among sexually active students who reported having had sexual contact with someone of the opposite sex (n = 2,698), most students (89.7%) had used a condom or a primary contraceptive method at last sexual intercourse. Prevalence of any condom use at last sexual intercourse was 54.3%, and condoms were the most prevalent primary contraceptive method (43.9% versus 23.3% for birth control pills; 4.8% for intrauterine device [IUD] or implant; and 3.3% for shot, patch, or ring). Approximately 9% had used condoms with an IUD, implant, shot, patch, ring, or birth control pills. Using no pregnancy prevention method was more common among non-Hispanic black (23.2%) and Hispanic (12.8%) students compared with non-Hispanic white students (6.8%); compared with Hispanic students, using no pregnancy prevention method was more common among non-Hispanic black students. Prevalence of condom use was consistently lower among students with other sexual risk behaviors. Results underscore the need for public health professionals to provide quality sexual and reproductive health education and clinical services for preventing unintended pregnancy and STDs/HIV and decreasing disparities among sexually active youths.

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.

BACKGROUND: Pathology and monkeypox virus (MPXV) tissue tropism in severe and fatal human mpox is not thoroughly described but can help elucidate the disease pathogenesis and the role of coinfections in immunocompromised patients. METHODS: We analyzed biopsy and autopsy tissues from 22 patients with severe or fatal outcomes to characterize pathology and viral antigen and DNA distribution in tissues by immunohistochemistry and in situ hybridization. Tissue-based testing for coinfections was also performed. RESULTS: Mucocutaneous lesions showed necrotizing and proliferative epithelial changes. Deceased patients with autopsy tissues evaluated had digestive tract lesions, and half had systemic tissue necrosis with thrombotic vasculopathy in lymphoid tissues, lung, or other solid organs. Half also had bronchopneumonia, and one-third had acute lung injury. All cases had MPXV antigen and DNA detected in tissues. Coinfections were identified in 5/16 (31%) biopsy and 4/6 (67%) autopsy cases. DISCUSSION: Severe mpox in immunocompromised patients is characterized by extensive viral infection of tissues and viremic dissemination that can progress despite available therapeutics. Digestive tract and lung involvement are common and associated with prominent histopathological and clinical manifestations. Coinfections may complicate mpox diagnosis and treatment. Significant viral DNA (likely correlating to infectious virus) in tissues necessitates enhanced biosafety measures in healthcare and autopsy settings.

Bartonella quintana infection is a vectorborne disease transmitted by the human body louse (1). In the United States, homelessness is the principal risk factor for B. quintana infection (2), likely attributable to limited access to hygiene facilities (1). This infection is not nationally notifiable in the United States, and its incidence is unknown. Acute B. quintana infection can cause fever, headache, and bone pain; severe manifestations include chronic bacteremia, bacillary angiomatosis, and infective endocarditis (3). Because the bacterium requires special conditions to grow in culture, standard blood cultures are usually negative (4). Diagnosis by serology is most common; however, cross-reactivity with other Bartonella species (e.g., B. henselae) can hamper interpretation. Molecular assays specific for B. quintana have been developed (5), but availability is limited to a few laboratories. Once diagnosed, infection can be cured by several weeks to months of antibiotic therapy.

BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None.

Effective services along the HIV continuum of care from HIV testing and counseling to linkage, and from linkage to antiretroviral therapy (ART) initiation and retention, are key to improved health outcomes of persons living with HIV. A comprehensive analysis of the costs and outcomes of cascade services is needed to help allocate and prioritize resources to achieve UNAIDS targets. We evaluated the costs and population-level impact of a community-wide, integrated scale-up of testing, linkage, and defaulter-tracing programs implemented in Bukoba Municipal Council, Tanzania. Costs per identified HIV-positive client for provider-initiated, and home- and venue-based testing and counseling were $92.64 United States dollars (USD), $256.33 USD, and $281.57 USD, respectively. Costs per patient linked to HIV care and ART were $47.69 USD and $74.12 USD, respectively, during all ART-eligibility periods combined. Costs per defaulter traced and returned to HIV care were $47.56 USD and $206.77 USD, respectively. The provider-initiated testing and counseling was the most cost-effective modality. Testing approaches targeted to populations groups and geographic location with high testing positivity rates may improve the overall efficiency of testing services. The expansion of ART eligibility criteria and high linkage rate also result in efficiency gains and economies of scale of linkage services.

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.

Background There is uncertainty about the burden of hospitalization associated with RSV and influenza in children, including those with underlying medical conditions.Methods We applied previously developed methodology (Goldstein et al., Epidemiology 2012) to HealthCare Cost and Utilization Project (HCUP) hospitalization data and additional data related to asthma diagnosis/previous history in hospitalized children to estimate RSV and influenza-associated hospitalization rates in different subpopulations of US children between 2003-2010.Results The estimated average annual rates (per 100,000 children) of RSV-associated hospitalization with a respiratory cause (ICD-9 codes 460-519) present anywhere in the discharge diagnosis were 2381 (95% CI(2252,2515)) in age <1y; 710.6(609.1,809.2) (age 1y); 395(327.7,462.4) (age 2y); 211.3(154.6,266.8) (age 3y); 111.1(62.4,160.1) (age 4y); 72.3(29.3,116.4) (ages 5-6y); 35.6(9.9,62.2) (ages 7-11y); and 39(17.5,60.6) (ages 12-17y).The corresponding rates of influenza-associated hospitalization were lower, ranging from 181(142.5,220.3) in age <1y to 17.9(11.7,24.2) in ages 12-17y. The relative risks for RSV-related hospitalization associated with a prior diagnosis of asthma in age groups under 5y ranged between 3.1(2.1,4.7) (age <1y) to 6.7(4.2,11.8) (age 2y); the corresponding risks for influenza-related hospitalization ranged from 2.8(2.1,4) (age <1y) to 4.9(3.8,6.4) (age 3y).Conclusions RSV-associated hospitalization rates in young children are high and decline rapidly with age. Young children with an asthma diagnosis should be target groups for RSV and influenza-related mitigation efforts, possibly including RSV prophylaxis for the youngest children.

During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic (1) . However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro , it provides a real competitive advantage in vivo , particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.

PURPOSE: We examined the impact of the COVID-19 pandemic in Fall 2021 on sexual and reproductive health (SRH) services among physicians whose practice provided these services to adolescents just before the pandemic. METHODS: Data were from the DocStyles online panel survey administered September-November 2021 to US physicians who reported their practice provided SRH services to adolescent patients before the pandemic (n = 948). We calculated prevalence of service delivery challenges (e.g., limited long-acting reversible contraception services) and use of strategies to support access (e.g., telehealth) in the month prior to survey completion, compared these estimates with prevalence "at any point during the COVID-19 pandemic", and examined differences by physician specialty and adolescent patient volume. RESULTS: Fewer physicians reported their practice experienced service delivery challenges in the month prior to survey completion than at any point during the pandemic. About 10% indicated limited long-acting reversible contraception and sexually transmitted infection testing services in the prior month overall; prevalence varied by physician specialty (e.g., 26% and 17%, respectively by service, among internists). Overall, about 25% of physicians reported reductions in walk-in hours, weekend/evening hours, and adolescents seeking care in the prior month. While most practices that initiated strategies supporting access to services during the pandemic used such strategies in the prior month, some practices (22%-37% depending on the strategy) did not. DISCUSSION: Findings suggest some physicians who serve adolescents continued to experience challenges providing SRH services in the Fall 2021, and some discontinued strategies to support access that had been initiated during the pandemic.

INTRODUCTION: Definitive vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been rarely reported. We present a case of a third trimester pregnancy with fetal distress necessitating cesarean section that demonstrated maternal, placental, and infant infection with the SARS-CoV-2 Alpha variant/B.1.1.7. METHODS: CDC's Influenza SARS-CoV-2 Multiplex RT-PCR Assay was used to test for SARS-CoV-2 in a maternal NP swab, maternal plasma, infant NP swab, and formalin-fixed paraffin-embedded (FFPE) placental tissue specimens. Whole genome sequencing (WGS) was performed on maternal plasma, infant, and placental specimens to determine the SARS-CoV-2 genotype. Histopathological evaluation, SARS-CoV-2 immunohistochemistry testing (IHC), and electron microscopy (EM) analysis were performed on placenta, umbilical cord, and membrane FFPE blocks. RESULTS: All specimens tested positive for SARS-CoV-2 by RT-PCR. WGS further revealed identical SARS-CoV-2 sequences from clade 20I/501Y.V1 (lineage Alpha/B.1.1.7) in maternal plasma, infant, and placental specimens. Histopathologic evaluation of the placenta showed histiocytic and neutrophilic intervillositis with fibrin deposition and trophoblast necrosis with positive SARS-CoV-2 immunostaining in the syncytiotrophoblast and electron microscopy evidence of coronavirus. DISCUSSION: These findings suggest vertical transmission of SARS-CoV-2, supported by clinical course timing, identical SARS-CoV-2 genotypes from maternal, placental, and infant samples, and IHC and EM evidence of placental infection. However, determination of the timing or distinction between prepartum and peripartum SARS-CoV-2 transmission remains unclear.

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority.

Information about state and local education policies regarding sexually transmitted infections, including human immunodeficiency virus, and unintended pregnancy prevention is available, yet less is known about school-level implementation of such policies. We examine trends in the percentage of US secondary schools teaching sexual and reproductive health (SRH) topics in a required course in Grades 6-8 and 9-12, including healthy relationships, sexual abstinence, condoms and condoms with other contraceptive methods. We analyze representative data from 38 states across six cycles of School Health Profiles (2008-18) assessed through self-administered questionnaires completed by lead health teachers. Logistic regression models examined linear trends in the percentages of schools teaching topics for Grades 6-8 and 9-12, separately. Trends were calculated for states having representative data for at least three cycles, including 2018. During 2008-18, it was more common to have increases in teaching how to obtain condoms, correct condom use and use condoms with other contraceptive methods in Grades 6-12 than decreases. More states showed decreases in teaching abstinence in Grades 6-12 than increases. Most states had no change in teaching SRH topics across grades. Findings suggest some improvement in school-based SRH education, yet efforts are needed to improve comprehensive, developmentally appropriate content.

OBJECTIVES: Determine whether Pre-Game Safety Huddles, a novel and low-resource approach to concussion education, increase the expected likelihood of concussion reporting for youth athletes. METHODS: A cluster-randomised trial compared Safety Huddles to usual care. Safety Huddles bring together athletes and coaches from both teams before the start of each game for coaches to briefly affirm the importance of speaking up if a concussion is suspected. Participants were athletes from 22 competitive community-based American football and girls and boys soccer teams (ages 9-14), and randomisation into intervention or control occurred at the level of the bracket (group of teams that compete against each other during the regular season). The primary outcome was expected likelihood of reporting concussion symptoms to the coach, measured via validated athlete survey at the beginning and end of the season. RESULTS: Of 343 eligible participants, 339 (99%) completed baseline surveys and 303 (88%) completed surveys at season end. The mean (SD) age was 11.4 (1.1) years, 26% were female soccer athletes, 27% were male soccer athletes and 47% were football athletes. In adjusted analyses accounting for baseline values and clustering by sport and team via random effects, expected likelihood of concussion reporting at the end of the season was significantly higher in the intervention group compared to controls (mean difference=0.49, 95% CI 0.11 to 0.88; Cohen's d=0.35). CONCLUSIONS AND RELEVANCE: Pre-Game Safety Huddles increased the expected likelihood of athletes reporting concussion symptoms. While further study is warranted, sport organisations should consider this approach a promising low-resource option for improving concussion safety in their setting. TRIAL REGISTRATION NUMBER: NCT04099329.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

On April 21, 2022, CDC issued a health advisory(†) encouraging U.S. clinicians to report all patients aged <10 years with hepatitis of unknown etiology to public health authorities, after identification of similar cases in both the United States (1) and Europe.(§) A high proportion of initially reported patients had adenovirus detected in whole blood specimens, thus the health advisory encouraged clinicians to consider requesting adenovirus testing, preferentially on whole blood specimens. For patients meeting the criteria in the health advisory (patients under investigation [PUIs]), jurisdictional public health authorities abstracted medical charts and interviewed patient caregivers. As of June 15, 2022, a total of 296 PUIs with hepatitis onset on or after October 1, 2021, were reported from 42 U.S. jurisdictions. The median age of PUIs was 2 years, 2 months. Most PUIs were hospitalized (89.9%); 18 (6.1%) required a liver transplant, and 11 (3.7%) died. Adenovirus was detected in a respiratory, blood, or stool specimen of 100 (44.6%) of 224 patients.(¶) Current or past infection with SARS-CoV-2 (the virus that causes COVID-19) was reported in 10 of 98 (10.2%) and 32 of 123 (26.0%) patients, respectively. No common exposures (e.g., travel, food, or toxicants) were identified. This nationwide investigation is ongoing. Further clinical data are needed to understand the cause of hepatitis in these patients and to assess the potential association with adenovirus.

During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.

OBJECTIVES: National guidelines call for annual testing for certain sexually transmitted infections (STIs) among specific adolescent populations, yet we have limited population-based data on STI testing prevalence among adolescents. With inclusion of a new item in the 2019 national Youth Risk Behavior Survey, we provide generalizable estimates of annual STI testing among sexually active high school students. METHODS: We report weighted prevalence estimates of STI testing (other than HIV) in the past 12 months among sexually active students (n = 2501) and bivariate associations between testing and demographic characteristics (sex, age, race and ethnicity, sexual identity, and sex of sexual contact). Multivariable models stratified by sex and adjusted for demographics examine the relationships between testing and sexual behaviors (age of initiation, number of sex partners, condom nonuse at last sexual intercourse, and substance use at last sexual intercourse). RESULTS: One-fifth (20.4%) of sexually active high school students reported testing for an STI in the previous year. A significantly higher proportion of female (26.1%) than male (13.7%) students reported testing. Among female students, prevalence differed by age (15 years = 12.6%, age 16 = 22.8%, age 17 = 28.5%, or 18 years = 36.9%). For male students, there were no differences by demographic characteristics, including sexual identity, but most sexual risk behaviors were associated with increased likelihood of STI testing (adjusted prevalence ratios ranging from 1.48 to 2.47). CONCLUSIONS: Low prevalence of STI testing suggests suboptimal adherence to national guidelines, particularly for sexually active adolescent females and young men who have sex with men who should be tested for Chlamydia and gonorrhea annually.

To the Editor.We read with concern the manuscript by Gill et al1 that described autopsy findings for 2 adolescents who died after COVID-19 vaccination. The authors correctly stated that the Centers for Disease Control and Prevention (CDC) performed testing for SARS-CoV-2 and found no evidence of SARS-CoV-2 infection in autopsy tissues from the decedents. However, the authors did not include findings from far more thorough immunohistochemical and molecular testing performed by the CDC for each patient. We believe that all of the CDC's findings should be considered carefully, and that the omission of these data has important implications for the conclusions of this paper.

Severe coronavirus disease in neonates is rare. We analyzed clinical, laboratory, and autopsy findings from a neonate in the United States who was delivered at 25 weeks of gestation and died 4 days after birth; the mother had asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and preeclampsia. We observed severe diffuse alveolar damage and localized SARS-CoV-2 by immunohistochemistry, in situ hybridization, and electron microscopy of the lungs of the neonate. We localized SARS-CoV-2 RNA in neonatal heart and liver vascular endothelium by using in situ hybridization and detected SARS-CoV-2 RNA in neonatal and placental tissues by using reverse transcription PCR. Subgenomic reverse transcription PCR suggested viral replication in lung/airway, heart, and liver. These findings indicate that in utero SARS-CoV-2 transmission contributed to this neonatal death.

IMPORTANCE: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear. OBJECTIVE: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. EXPOSURES: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). MAIN OUTCOMES AND MEASURES: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. RESULTS: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). CONCLUSIONS AND RELEVANCE: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.

Equitable access to high quality adolescent sexual and reproductive health (ASRH) services can help reduce unintended pregnancies, sexually transmitted diseases, and disparities in these outcomes. The Centers for Disease Control and Prevention (CDC), Division of Reproductive Health, has a long history of working to improve access to and quality of ASRH services through applied research and public health practice. This report from CDC summarizes the evolution of these efforts from more than a decade of work-from community-based demonstration projects to an initiative to support wide-scale implementation. We describe a community-wide teen pregnancy prevention program model that includes a component addressing ASRH services (2010-2015), focused efforts related to quality improvement (QI) of and community-clinic linkages to ASRH services (2015-2020), and the development of a QI package that collates implementation strategies and tools to improve ASRH services (2020-2022). We conclude by discussing future directions. In disseminating key strategies and resources from this work, we aim to support broader public health and clinical efforts to strengthen ASRH care in the United States in ways that promote health equity.