Safety and Immunogenicity of an mRNA-1273 Booster in Children.

BACKGROUND: A 2-dose mRNA-1273 primary series in children aged 6 months-5 years (25-µg) and 6-11 years (50-µg) had an acceptable safety profile and was immunogenic in the phase 2/3 KidCOVE study. We present data from KidCOVE participants who received an mRNA-1273 booster dose. METHODS: An mRNA-1273 booster dose (10-µg for children aged 6 months-5 years; 25-µg for children aged 6-11 years; age groups based on participant age at enrollment) was administered ≥6 months after primary series completion. The primary safety objective was the safety and reactogenicity of an mRNA-1273 booster dose. The primary immunogenicity objective was to infer efficacy of an mRNA-1273 booster dose by establishing noninferiority of neutralizing antibody (nAb) responses after a booster in children compared with nAb responses observed after the mRNA-1273 primary series in young adults (18-25 years) from the pivotal efficacy study. Data were collected from March 2022 to June 2023. RESULTS: Overall, 153 (6 months-5 years) and 2519 (6-11 years) participants received an mRNA-1273 booster dose (median age at receipt of booster: 2 and 10 years, respectively). The booster dose safety profile was generally consistent with that of the primary series in children; no new safety concerns were identified. An mRNA-1273 booster dose elicited robust nAb responses against ancestral SARS-CoV-2 among children and met prespecified noninferiority success criteria when compared with responses observed after the primary series in young adults. CONCLUSIONS: Safety and immunogenicity data support administration of a mRNA-1273 booster dose in children aged 6 months to 11 years. CLINICAL TRIALS REGISTRATION: NCT04796896.

Randomized Controlled Trial of a Remote Coaching mHealth Adherence Intervention in Youth Living with HIV.

Youth living with HIV (YLWH) in the US have low rates of viral suppression (VS). In a prospective randomized clinical trial (ATN152) that enrolled 89 YLWH on antiretroviral therapy (ART) with detectable viral load, we evaluated a 12 week triggered escalating real-time adherence (TERA) intervention with remote coaching, electronic dose monitoring (EDM), and outreach for missed/delayed doses compared to standard of care (SOC). Median [Q1, Q3] percent days with EDM opening was higher in TERA (72% (47%, 89%)) versus SOC (41% (21%, 59%); p < 0.001) and incidence of numbers of 7 day gaps between openings were lower (TERA to SOC ratio: 0.40; 95% CI 0.30, 0.53; p < 0.001). There were no differences in VS at week 12 (TERA 35%; 95% CI 21%, 51% versus SOC 36%; 95% CI 22%, 51%; p > 0.99) or later time-points. The intervention improved adherence but not VS in heavily ART-experienced YLWH. Remote coaching more closely tailored to the unique dosing patterns and duration of need for youth struggling to reach VS warrants further investigation.

Safety, Tolerability, and Pharmacokinetics of a Long-Acting Broadly Neutralizing Human Immunodeficiency Virus Type 1 (HIV-1) Monoclonal Antibody VRC01LS in HIV-1-Exposed Newborn Infants.

BACKGROUND: Perinatal human immunodeficiency virus type 1 (HIV-1) continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs). METHODS: An extended half-life bNAb, VRC01LS, was administered subcutaneously at 80 mg/dose after birth to HIV-1-exposed, nonbreastfed (cohort 1, n = 10) and breastfed (cohort 2, n = 11) infants. Cohort 2 received a second dose (100 mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort. RESULTS: Local reactions (all grade ≤2) occurred in 67% and 20% after dose 1 and dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administered subcutaneously achieved a mean (standard deviation) plasma level of 222.3 (71.6) µg/mL by 24 hours and 44.0 (11.6) µg/mL at week 12, prior to dose 2. The preestablished target of ≥50 µg/mL was attained in 95% and 32% at weeks 8 and 12, respectively. The terminal half-life was 37-41 days. VRC01LS level after 1 dose was significantly greater (P <.002) than after a VRC01 dose (20 mg/kg). No infants acquired HIV-1. CONCLUSIONS: VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.

Infections after Natural Disasters.

Natural disasters, particularly flooding, are associated with many environmental changes, and the chances of infections after a disaster increase. Dead bodies are not associated with increased infections, but many other factors contribute to the increase in infections and possible outbreaks. This article discusses the factors associated with increased risk of infections and the types of infections that may occur after a natural disaster. This article also presents a brief discussion of infection prevention and mitigation after a natural disaster.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

The Impact of Housing and HIV Treatment on Health-Related Quality of Life Among People With HIV Experiencing Homelessness or Unstable Housing.

Objectives. To determine the impact of improvements in housing and HIV clinical parameters on health-related quality of life (HRQOL) in persons with HIV infection experiencing homelessness.Methods. This prospective cohort study took place in 9 US sites. Local efforts sought to improve HIV and housing status. Longitudinal data analyses determined the impact of changes in housing status, HIV suppression, and CD4 cell counts on HRQOL at 12 months, measured as mental and physical component summary scores.Results. Among 909 participants enrolled from 2013 to 2016, 75.1% were homeless, 51.6% did not have HIV suppression, and 23.6% had a CD4 count less than 200 cells per cubic millimeter. Median mental and physical component summary scores were 35.4 and 38.9, respectively. These 5 parameters all improved by 6 months. In multivariate modeling, maintaining or achieving stable housing predicted higher PCS at 12 months, but CD4 count and HIV suppression improvements did not. Improvements in housing, CD4 count, and HIV suppression did not predict mental component score at 12 months.Conclusions. Housing and HIV treatment are necessary but not sufficient to improve HRQOL in this challenging population. The high prevalence of socioeconomic and mental health needs we found support the call for patient-centered comprehensive care.

Improving Adolescent Health Risk Assessment: A Multi-method Pilot Study.

Objectives Given poor compliance by providers with adolescent health risk assessment (HRA) in primary care, we describe the development and feasibility of using a health information technology (HIT)-enhanced HRA to improve the frequency of HRAs in diverse clinical settings, asking adolescents' recall of quality of care as a primary outcome. Methods We conducted focus groups and surveys with key stakeholders (Phase I) , including adolescents, clinic staff and providers to design and implement an intervention in a practice-based research network delivering private, comprehensive HRAs via tablet (Phase II). Providers and adolescents received geo-coded community resources according to individualized risks. Following the point-of-care implementation , we collected patient-reported outcomes using post-visit quality surveys (Phase III). Patient-reported outcomes from intervention and comparison clinics were analyzed using a mixed-model, fitted separately for each survey domain. Results Stakeholders agreed upon an HIT-enhanced HRA (Phase I). Twenty-two academic and community practices in north-central Florida then recruited 609 diverse adolescents (14-18 years) during primary care visits over 6 months; (mean patients enrolled = 28; median = 20; range 1-116; Phase II). Adolescents receiving the intervention later reported higher receipt of confidential/private care and counseling related to emotions and relationships (adjusted scores 0.42 vs 0.08 out of 1.0, p < .01; 0.85 vs 0.57, p < .001, respectively, Phase III) than those receiving usual care. Both are important quality indicators for adolescent well-child visits. Conclusions Stakeholder input was critical to the acceptability of the HIT-enhanced HRA. Patient recruitment data indicate that the intervention was feasible in a variety of clinical settings and the pilot evaluation data indicate that the intervention may improve adolescents' perceptions of high quality care.

Vitamin D Deficiency in HIV-Infected Children.

OBJECTIVES: Improvement in life expectancy with the use of combination antiretroviral therapy has come with the recognition of the complications associated with chronic human immunodeficiency virus infection. Vitamin D has been of particular interest because of its effect on bone health and immune functions. The purpose of this study was to assess vitamin D status in children in relation to the duration and severity of their human immunodeficiency virus infection and nutritional status, as well as to determine whether there was any effect of seasonality. METHODS: The study design was cross-sectional and all children 0 to 21 years of age were eligible to participate. RESULTS: A total of 59 participants provided informed consent, with 54 subjects completing all study activities. Thirteen (24.1%) had sufficient vitamin D levels, 13 (24.1%) had insufficient levels, and 28 (51.9%) had deficient levels per the guidelines of the Endocrine Society. In our univariate analysis, younger age was associated with higher vitamin D levels (P = 0.030). Higher CD4 counts were associated with higher vitamin D levels (P = 0.018). A significant association between the vitamin D intake per day and vitamin D level was seen (P = 0.013). In the multivariate analysis, the best ordinal logistic regression model had the CD4 count as predictor (P < 0.005), higher CD4 counts were associated with decreased odds of vitamin D deficiency (odds ratio 0.47, 95% confidence interval 0.28-0.80). CONCLUSIONS: Vitamin D deficiency was common among the patients included in this study.

Oral acyclovir suppression and neurodevelopment after neonatal herpes.

BACKGROUND: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS: We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS: A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09). CONCLUSIONS: Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).

Evolutionarily conserved epitopes on human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus reverse transcriptases detected by HIV-1-infected subjects.

Anti-human immunodeficiency virus (HIV) cytotoxic T lymphocyte (CTL)-associated epitopes, evolutionarily conserved on both HIV type 1 (HIV-1) and feline immunodeficiency virus (FIV) reverse transcriptases (RT), were identified using gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and carboxyfluorescein diacetate succinimide ester (CFSE) proliferation assays followed by CTL-associated cytotoxin analysis. The peripheral blood mononuclear cells (PBMC) or T cells from HIV-1-seropositive (HIV(+)) subjects were stimulated with overlapping RT peptide pools. The PBMC from the HIV(+) subjects had more robust IFN-γ responses to the HIV-1 peptide pools than to the FIV peptide pools, except for peptide-pool F3. In contrast, much higher and more frequent CD8(+) T-cell proliferation responses were observed with the FIV peptide pools than with the HIV peptide pools. HIV-1-seronegative subjects had no proliferation or IFN-γ responses to the HIV and FIV peptide pools. A total of 24% (40 of 166) of the IFN-γ responses to HIV pools and 43% (23 of 53) of the CD8(+) T-cell proliferation responses also correlated to responses to their counterpart FIV pools. Thus, more evolutionarily conserved functional epitopes were identified by T-cell proliferation than by IFN-γ responses. In the HIV(+) subjects, peptide-pool F3, but not the HIV H3 counterpart, induced the most IFN-γ and proliferation responses. These reactions to peptide-pool F3 were highly reproducible and persisted over the 1 to 2 years of testing. All five individual peptides and epitopes of peptide-pool F3 induced IFN-γ and/or proliferation responses in addition to inducing CTL-associated cytotoxin responses (perforin, granzyme A, granzyme B). The epitopes inducing polyfunctional T-cell activities were highly conserved among human, simian, feline, and ungulate lentiviruses, which indicated that these epitopes are evolutionarily conserved. These results suggest that FIV peptides could be used in an HIV-1 vaccine.

A Case of Congenital Syphilis Diagnosed in an Infant Past the Newborn Period.

This case report highlights the need for syphilis re-testing during pregnancy and at labor and delivery when there are high-risk factors present. Our patient, an infant, was evaluated for non-accidental trauma because of the presence of multiple fractures, which could be one of the presentations of congenital syphilis. A high index of suspicion is required for syphilis when an infant presents with multiple fractures. Syphilis testing and re-testing guidelines should be followed strictly so that pregnant women are appropriately treated to prevent congenital syphilis.

Traveling Does More Than Widen One's Horizon: Travel History as Key to Diagnosing Blastomycosis.

This case report highlights the importance of a detailed travel history and the need to revisit the differential diagnosis when there is an unexpected clinical course. A previously healthy 15-year-old male presented to a hospital in Florida with a fever, cough, and shortness of breath. He was seen multiple times at urgent care centers and treated with steroids and antibiotics for community-acquired pneumonia (CAP). The patient's chest X-rays and CT showed necrotizing pneumonia with pleural effusion, which required a chest tube. Despite broadening coverage for possible resistant organisms, his fevers and hypoxia continued. On day 14 of hospitalization, a bronchoscopy was performed, which led to the diagnosis of blastomycosis. History was revisited, and a specific travel history was obtained. The patient had been camping with his father on the Minnesota/Canada border a few months prior to his presentation. Blastomycosis is caused by a dimorphic fungus endemic in certain parts of the United States including areas surrounding the Mississippi and Ohio River valleys, some southeastern states, and areas bordering the Great Lakes. Autochthonous blastomycosis is not seen in Florida. The infection is acquired by inhalation of the organism and is associated with outdoor occupation and recreation. As with other infections with specific endemic distribution, the diagnosis of blastomycosis can be delayed if the epidemiologic link is not established. Questions about travel history need to be very specific as this could be critical in establishing the appropriate differential diagnosis and leading the workup. The patient's lack of improvement despite appropriate antibiotic therapy for CAP led to questioning the working diagnosis, revisiting the history, and expanding the workup, which was critical in this case.

The Many Faces of Neurological Neonatal Herpes Simplex Virus Infection.

This case series explores the various manifestations of central nervous system (CNS) involvement in neonatal herpes simplex virus (HSV) infection and highlights the challenges involved in their diagnosis and treatment. Neonatal HSV infection is a rare but serious condition that can have significant neurological consequences. The article presents three cases of neonatal HSV infection, all involving the CNS, each characterized by distinct clinical features and outcomes. Case 1 describes a three-week-old male with severe HSV meningoencephalitis resulting in poor response to treatment and death. Cases 2 and 3 describe younger neonates who presented early in the disease course with disseminated infection and skin, eye, and mouth (SEM) lesions. Although both patients had CNS involvement, their outcomes were remarkably favorable. The wide range of clinical presentations of CNS manifestations in neonatal HSV infection, ranging from nonspecific to evident neurological symptoms, underscores the need for a high index of suspicion and comprehensive evaluation to ensure early diagnosis and appropriate treatment. However, it also notes that even with timely treatment, some cases may still have a poor prognosis.

Prevalence of asymptomatic cytomegalovirus (CMV) infection in newborns in northeast Florida.

Background: Congenital cytomegalovirus (CMV) infection is the leading cause of hearing loss and neurocognitive delay among children. Affected infants may be asymptomatic at birth and even pass their universal hearing screen. Early identification of CMV-infected infants will allow earlier detection, evaluation and management. The prevalence of congenital CMV infection in the developed world varies geographically from 0.6% to 0.7% of all deliveries and certain regions are at higher risk. The prevalence of congenital CMV is unknown for our region. Aim: The purpose of this study was to determine the prevalence of CMV infection among the neonatal population at an urban, tertiary hospital in northeast Florida which serves a large population of patients with low socioeconomic status to assess if universal screening program for congenital asymptomatic CMV infection can be determined. Methods: The study was submitted and approved by our Institutional Review Board. We tested the urine for CMV infection in 100 asymptomatic newborns (>32 weeks gestational age and >1,750 g weight at the time of delivery) delivered between June 2016 and July 2017. Results: Urine CMV was tested on 100 infants. One infant had a positive urine NAAT for CMV, making the prevalence of congenital CMV infection among asymptomatic newborns in our hospitals' population 1%. Conclusion: CMV prevalence in our setting of an urban, tertiary hospital is relatively consistent with the national average of all congenital CMV infections. A policy of universal screening for congenital CMV may be necessary.

Risk Factors for Perinatal Transmission of Hepatitis C Virus.

OBJECTIVE: To estimate the rate of perinatal transmission of hepatitis C virus (HCV) infection, to identify risk factors for perinatal transmission of HCV infection, and to determine the viremic threshold for perinatal transmission. METHODS: This was a prospective, multicenter, observational study of pregnant individuals at less than 24 weeks of gestation screened for HCV infection from 2012 to 2018 in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Individuals found to be HCV antibody-positive were followed throughout pregnancy. Children were followed for evidence of perinatal transmission at 2-6 months (HCV RNA testing) and at 18-24 months (HCV RNA and antibody testing) of life. The primary outcome was perinatal transmission, defined as positive test results at either follow-up time point. RESULTS: A total of 109,379 individuals were screened for HCV infection. Of the 1,224 participants who screened positive, 772 (63.1%) enrolled and 432 of those 772 (56.0%) had data available to assess primary outcome. The overall rate of perinatal transmission was 6.0% (26/432, 95% CI 4.0-8.7%). All children with HCV infection were born to individuals with demonstrable viremia. In viremic participants (n=314), the perinatal transmission rate was 8.0% (95% CI 5.2-11.5%). Risk factors for perinatal transmission included HCV RNA greater than 106 international units/mL (adjusted odds ratio [aOR] 8.22, 95% CI 3.16-21.4) and vaginal bleeding reported at any time before delivery (aOR 3.26, 95% CI 1.32-8.03). A viremic threshold for perinatal transmission could not be established. CONCLUSION: Perinatal transmission of HCV infection was limited to viremic individuals. High viral loads and antepartum bleeding were associated with perinatal transmission.