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BackgroundThe purpose of this study was to estimate prevalence of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients admitted to obstetric inpatient units throughout the United States as detected by universal screening. We sought to describe the relationship between obstetric inpatient asymptomatic infection rates and publicly available surrounding community infection rates.MethodsA cross-sectional study in which medical centers reported rates of positive SARS-CoV-2 testing in asymptomatic pregnant and immediate postpartum patients over a 1-3-month time span in 2020. Publicly reported SARS-CoV-2 case rates from the relevant county and state for each center were collected from the COVID Act Now dashboard and the COVID Tracking Project for correlation analysis.ResultsData were collected from 9 health centers, encompassing 18 hospitals. Participating health centers were located in Alabama, California, Illinois, Louisiana, New Jersey, North Carolina, Pennsylvania, Rhode Island, Utah, and Washington State. Each hospital had an active policy for universal SARS-CoV-2 testing on obstetric inpatient units. A total of 10 147 SARS-CoV-2 tests were administered, of which 124 were positive (1.2%). Positivity rates varied by site, ranging from 0-3.2%. While SARS-CoV-2 infection rates were lower in asymptomatic obstetric inpatient groups than the surrounding communities, there was a positive correlation between positivity rates in obstetric inpatient units and their surrounding county (P=.003, r=.782) and state (P=.007, r=.708).ConclusionsGiven the correlation between community and obstetric inpatient rates, the necessity of SARS-CoV-2-related healthcare resource utilization in obstetric inpatient units may be best informed by surrounding community infection rates.

BackgroundThe WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population.MethodsIn this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895.FindingsWe identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (

Clinical trials of pharmacologic treatments of coronavirus disease 2019 (COVID-19) are being rapidly designed and implemented in adults. Children are often not considered during development of novel treatments for infectious diseases until very late. Although children appear to have a lower risk compared with adults of severe COVID-19 disease, a substantial number of children globally will benefit from pharmacologic treatments. It will be reasonable to extrapolate efficacy of most treatments from adult trials to children. Pediatric trials should focus on characterizing a treatment's pharmacokinetics, optimal dose, and safety across the age spectrum. These trials should use an adaptive design to efficiently add or remove arms in what will be a rapidly evolving treatment landscape, and should involve a large number of sites across the globe in a collaborative effort to facilitate efficient implementation. All stakeholders must commit to equitable access to any effective, safe treatment for children everywhere.

Background: Isoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure. Methods: The infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6–10 weeks, birthweight ≥2.5 kg, and gestation ≥37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms. Results: Among 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0–3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ (β = 0.04 [95% CI:-0.14, 0.22]), HAZ (β = 0.14 [95% CI:-0.06, 0.34]), and WHZ [β = -0.07 [95% CI:-0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase (β to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm. Conclusion: IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life. [ABSTRACT FROM AUTHOR]

Background Hybrid immunity (infection plus vaccination) may increase maternally derived SARS-CoV-2 antibody responses and durability versus infection alone. Methods Prospective cohort of pregnant participants with prior SARS-CoV-2 infection (anti-nucleocapsid IgG, RT-PCR, or antigen positive) and their infants had blood collected in pregnancy, at delivery/birth, and postpartum tested for anti-spike (anti-S) IgG and neutralizing antibodies (neutAb). Results Among 107 participants at enrollment, 40% were unvaccinated and 60% were vaccinated (received ≥1 dose); 102 had previous SARS-CoV-2 infection in pregnancy (median, 19 weeks' gestation); 5 were diagnosed just prior to pregnancy (median, 8 weeks). At delivery, fewer unvaccinated participants (87% anti-S IgG+, 86% neutAb) and their infants (86% anti-S IgG+, 75% neutAb) had anti-S IgG+ or neutAb compared to vaccinated participants and their infants (100%, P ≤.01 for all). By 3–6 months postpartum, 50% of infants of unvaccinated participants were anti-S IgG+ and 14% had neutAb, versus 100% among infants of vaccinated participants (all P <.01), with lower median antibody responses (anti-S IgG log10 1.95 vs 3.84 AU/mL, P <.01; neutAb log10 1:1.34 vs 1:3.20, P =.11). Conclusions In pregnant people with prior SARS-CoV-2, vaccination before delivery provided more durable maternally derived antibody responses than infection alone in infants through 6 months. [ABSTRACT FROM AUTHOR]

INTRODUCTION Tuberculosis (TB) is a leading cause of death among people living with HIV [1, 2] and a significant cause of morbidity and mortality in children living with HIV (CLHIV) [...], : Introduction: Isoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited. Methods: We evaluated the IPT cascade among CLHIV aged Results: Overall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97?99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1?3) were ineligible due to active TB and 828 (98%; 95% CI 97?99) were eligible. Five hundred and fifty?nine (68%; 95% CI 64?71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5?10.2). Overall, 434 (78%; 95% CI 74?81) IPT initiators completed. Attending high?volume HIV clinics (aRR = 2.82; 95% CI 1.20?6.62) was independently associated with IPT non?initiation. IPT non?initiation had a trend of being higher among those enrolled in the period 2017?2019 versus 2015?2016 (aRR = 1.91; 0.98?3.73) and those who were HIV virally non?suppressed (aRR = 1.90; 95% CI 0.98?3.71). Being enrolled in 2017?2019 versus 2015?2016 (aRR = 1.40; 1.01?1.96) was independently associated with IPT non?completion. By 24 months after IPT screening, TB incidence was four?fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08?17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82?23.56). Conclusions: Despite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop?offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6?month course to reduce TB in CLHIV.

To end the tuberculosis (TB) epidemic, the World Health Organization (WHO) recommends improving access to testing and treatment of latent TB infection (LTBI) [1]. Despite recent epidemiologic studies demonstrating an [...], Keywords: tuberculosis; prevention; pregnant; HIV; isoniazid; postpartum

Background Pregnancy and human immunodeficiency virus (HIV) may influence tuberculosis infection detection using interferon (IFN)-γ release assay (QFT-Plus; Qiagen) and tuberculin skin test (TST). Methods Participants in Western Kenya underwent QFT-Plus and TST in pregnancy, 6 weeks postpartum (6wkPP) and 12 months postpartum (12moPP). Results 400 participants (200 with HIV [WHIV], 200 HIV-negative) enrolled during pregnancy (median 28 weeks' gestation [interquartile range, 24–30]). QFT-Plus positivity prevalence was higher than TST in pregnancy (32.5% vs 11.6%) and through 12moPP (6wkPP, 30.9% for QFT-Plus vs 18.0% for TST; 12moPP, 29.5% vs 17.1%; all P <.001), driven primarily by QFT-Plus–positive/TST-negative discordance among HIV-negative women. Tuberculosis infection test conversion incidence was 28.4/100 person-years (PY) and higher in WHIV than HIV-negative women (35.5 vs 20.9/100 PY; hazard ratio, 1.73 [95% confidence interval, 1.04–2.88]), mostly owing to early postpartum TST conversion among WHIV. Among QFT-Plus–positive participants in pregnancy, Mycobacterium tuberculosis   (Mtb) –specific IFN-γ responses were dynamic through 12moPP and lower among WHIV than HIV-negative women with tuberculosis infection at all time points. Conclusions QFT-Plus had higher diagnostic yield than TST in peripartum women. Peripartum QFT-Plus positivity was stable and less influenced by HIV than TST. Mtb –specific IFN-γ responses were dynamic and lower among WHIV. Tuberculosis infection test conversion incidence was high between pregnancy and early postpartum, potentially owing to postpartum immune recovery. [ABSTRACT FROM AUTHOR]

A study published in the Journal of Infectious Diseases found that hybrid immunity, which is a combination of natural infection and vaccination, provides more durable antibody responses in infants compared to infection or vaccination alone. The study enrolled 107 participants with prior SARS-CoV-2 infection during pregnancy, with 70 having hybrid immunity and 37 having infection alone. Blood samples collected from the participants and their infants showed that those with hybrid immunity had higher levels of antibodies compared to those with infection or vaccination alone. The study suggests that vaccination is beneficial for pregnant individuals, even if they have had a prior infection, to provide additional protection for themselves and their infants. [Extracted from the article]