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Understanding persistence of humoral immune responses elicited by vaccination against coronavirus disease 2019 (COVID-19) is critical for informing the duration of protection and appropriate booster timing. We developed a mechanistic model to characterize the time course of humoral immune responses in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-seronegative adults after primary vaccination with the Janssen COVID-19 vaccine, Ad26.COV2.S. The persistence of antibody responses was quantified through mechanistic modeling-based simulations. Two biomarkers of humoral immune responses were examined: SARS-CoV-2 neutralizing antibodies determined by wild-type virus neutralization assay (wtVNA) and spike protein-binding antibodies determined by indirect spike protein enzyme-linked immunosorbent assay (S-ELISA). The persistence of antibody responses was defined as the period of time during which wtVNA and S-ELISA titers remained above the lower limit of quantification. A total of 442 wtVNA and 1,185 S-ELISA titers from 82 and 220 participants, respectively, were analyzed following administration of a single dose of Ad26.COV2.S (5 × 10

Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose.ENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing.Enrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36·0 (15·0-62·0) days. Vaccine efficacy was 75·2% (adjusted 95% CI 54·6-87·3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55·6%] of 3015 vs 896 [57·5%] of 1559, respectively; systemic adverse events, 1764 [58·5%] of 3015 vs 821 [52·7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity.A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed.Janssen ResearchDevelopment.

The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation.In an international, randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned adult participants in a 1:1 ratio to receive a single dose of Ad26.COV2.S (5×10The per-protocol population included 19,630 SARS-CoV-2-negative participants who received Ad26.COV2.S and 19,691 who received placebo. Ad26.COV2.S protected against moderate to severe-critical Covid-19 with onset at least 14 days after administration (116 cases in the vaccine group vs. 348 in the placebo group; efficacy, 66.9%; adjusted 95% confidence interval [CI], 59.0 to 73.4) and at least 28 days after administration (66 vs. 193 cases; efficacy, 66.1%; adjusted 95% CI, 55.0 to 74.8). Vaccine efficacy was higher against severe-critical Covid-19 (76.7% [adjusted 95% CI, 54.6 to 89.1] for onset at ≥14 days and 85.4% [adjusted 95% CI, 54.2 to 96.9] for onset at ≥28 days). Despite 86 of 91 cases (94.5%) in South Africa with sequenced virus having the 20H/501Y.V2 variant, vaccine efficacy was 52.0% and 64.0% against moderate to severe-critical Covid-19 with onset at least 14 days and at least 28 days after administration, respectively, and efficacy against severe-critical Covid-19 was 73.1% and 81.7%, respectively. Reactogenicity was higher with Ad26.COV2.S than with placebo but was generally mild to moderate and transient. The incidence of serious adverse events was balanced between the two groups. Three deaths occurred in the vaccine group (none were Covid-19-related), and 16 in the placebo group (5 were Covid-19-related).A single dose of Ad26.COV2.S protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe-critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of Covid-19 vaccines. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.).

The Ad26.COV2.S vaccine was highly effective against severe-critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis.We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×10Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe-critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe-critical Covid-19 (with only 4 severe-critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19-related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified.A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe-critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.).

Ad26.COV2.S is a well-tolerated and effective vaccine against COVID-19. We evaluated durability of anti-SARS-CoV-2 antibodies elicited by single-dose Ad26.COV2.S and the impact of boosting.In randomized, double-blind, placebo-controlled, phase 1/2a and phase 2 trials, participants received single-dose Ad26.COV2.S (5 × 10Data were analyzed from phase 1/2a participants enrolled from 22 July-18 December 2020 (Cohort 1a, 18-55 years [y], N = 25; Cohort 2a, 18-55y, N = 17; Cohort 3, ≥65y, N = 22), and phase 2 participants from 14 to 22 September 2020 (18-55y and ≥ 65y, N = 73). Single-dose Ad26.COV2.S elicited stable neutralizing antibodies for at least 8-9 months and stable binding antibodies for at least 6 months, irrespective of age. A 5 × 10Single-dose Ad26.COV2.S elicited durable antibody responses for at least 8 months and elicited immune memory. Booster-elicited binding and neutralizing antibody responses were rapid and robust, even with a quarter vaccine dose, and stronger with a longer interval since primary vaccination.ClinicalTrials.gov Identifier: NCT04436276, NCT04535453.

Background Tuberculosis preventive therapy for persons with HIV infection is effective, but its durability is uncertain. Objective To compare treatment completion rates of weekly isoniazid-rifapentine for 3 months versus daily isoniazid for 6 months as well as the effectiveness of the 3-month rifapentine-isoniazid regimen given annually for 2 years versus once. Design Randomized trial. (ClinicalTrials.gov: NCT02980016). Setting South Africa, Ethiopia, and Mozambique. Participants Persons with HIV infection who were receiving antiretroviral therapy, were aged 2 years or older, and did not have active tuberculosis. Intervention Participants were randomly assigned to receive weekly rifapentine-isoniazid for 3 months, given either annually for 2 years or once, or daily isoniazid for 6 months. Participants were screened for tuberculosis symptoms at months 0 to 3 and 12 of each study year and at months 12 and 24 using chest radiography and sputum culture. Measurements Treatment completion was assessed using pill counts. Tuberculosis incidence was measured over 24 months. Results Between November 2016 and November 2017, 4027 participants were enrolled; 4014 were included in the analyses (median age, 41 years; 69.5% women; all using antiretroviral therapy). Treatment completion in the first year for the combined rifapentine-isoniazid groups (n = 3610) was 90.4% versus 50.5% for the isoniazid group (n = 404) (risk ratio, 1.78 [95% CI, 1.61 to 1.95]). Tuberculosis incidence among participants receiving the rifapentine-isoniazid regimen twice (n = 1808) or once (n = 1802) was similar (hazard ratio, 0.96 [CI, 0.61 to 1.50]). Limitation If rifapentine-isoniazid is effective in curing subclinical tuberculosis, then the intensive tuberculosis screening at month 12 may have reduced its effectiveness. Conclusion Treatment completion was higher with rifapentine-isoniazid for 3 months compared with isoniazid for 6 months. In settings with high tuberculosis transmission, a second round of preventive therapy did not provide additional benefit to persons receiving antiretroviral therapy. Primary funding source The U.S. Agency for International Development through the CHALLENGE TB grant to the KNCV Tuberculosis Foundation.

Mathematical models are increasingly being used to compare strategies for tuberculosis (TB) control and inform policy decisions. Models often do not consider financial and other constraints on implementation and may overestimate the impact that can be achieved. We developed a pragmatic approach for incorporating resource constraints into mathematical models of TB. Using a TB transmission model calibrated for South Africa, we estimated the epidemiologic impact and resource requirements (financial, human resource (HR), and diagnostic) of 9 case-finding interventions. We compared the model-estimated resources with scenarios of future resource availability and estimated the impact of interventions under these constraints. Without constraints, symptom screening in public health clinics and among persons receiving care for human immunodeficiency virus infection was predicted to lead to larger reductions in TB incidence (9.5% (2.5th–97.5th percentile range (PR), 8.6–12.2) and 14.5% (2.5th–97.5th PR, 12.2–16.3), respectively) than improved adherence to diagnostic guidelines (2.7%; 2.5th–97.5th PR, 1.6–4.1). However, symptom screening required large increases in resources, exceeding future HR capacity. Even under our most optimistic HR scenario, the reduction in TB incidence from clinic symptom screening was 0.2%–0.9%—less than that of improved adherence to diagnostic guidelines. Ignoring resource constraints may result in incorrect conclusions about an intervention’s impact and may lead to suboptimal policy decisions. Models used for decision-making should consider resource constraints.

Summary Background Tuberculosis is the leading single-pathogen cause of death worldwide, and China has the third largest number of cases worldwide. New tools, such as new vaccines, are needed to meet WHO tuberculosis goals. Tuberculosis vaccine development strategies mostly target infants or adolescents, but given China's ageing epidemic, vaccinating older people might be important. We modelled the potential impact of new tuberculosis vaccines in China targeting adolescents (15–19 years) or older adults (60–64 years) with varying vaccine characteristics to inform strategic vaccine development. Methods A Mycobacterium tuberculosis transmission model was calibrated to age-stratified demographic and epidemiological data from China. Varying scenarios of vaccine implementation (age targeting [adolescents or older adults] and coverage [30% or 70%]) and characteristics (efficacy [40%, 60%, or 80%], duration of protection [10 years or 20 years], and host infection status required for efficacy [pre-infection, post-infection in latency, post-infection in latency or recovered, or pre-infection and post-infection]) were assessed. Primary outcomes were tuberculosis incidence and mortality rate reduction in 2050 in each vaccine scenario compared with the baseline (no new vaccine) scenario and cumulative number needed to vaccinate (NNV) per case or death averted, 2025–50. Findings By 2050, results suggest that 74·5% (uncertainty interval [UI] 70·2–78·6) of incident tuberculosis cases in China would occur in people aged 65 years or older, and 75·1% (66·8–80·7) of all cases would be due to reactivation, rather than new infection. All vaccine profiles delivered to older adults had higher population-level impact (reduction of incidence and mortality rates) and lower NNV per case and per death averted than if delivered to adolescents. For an intermediate vaccine scenario of 60% efficacy, 10-year protection, and 70% coverage, the reduction of tuberculosis incidence rates with older adult vaccination was 1·9 times (UI 1·5–2·6) to 157·5 times (119·3–225·6) greater than with adolescent vaccination, and the NNV was 0·011 times (0·008–0·014) to 0·796 times (0·632–0·970) lower. Furthermore, with older adult vaccination, post-infection vaccines provided substantially greater mortality and incidence rate reductions than pre-infection vaccines. Interpretation Adolescent-targeted tuberculosis vaccines, the focus of many development plans, would have only a small impact in ageing, reactivation-driven epidemics such as those in China. Instead, an efficacious post-infection vaccine delivered to older adults will be crucial to maximise population-level impact in this setting and would provide an important contribution towards achieving WHO goals. Older adults should be included in tuberculosis vaccine clinical development and implementation planning. Funding Aeras and UK MRC.

IntroductionAccurate tuberculosis (TB) incidence and optimal surveillance strategies are pertinent to TB vaccine trial design. Infants are a targeted population for new TB vaccines, but data from India, with the highest global burden of TB cases, is limited.MethodsIn a population-based prospective trial conducted between November 2006 and July 2008, BCG-vaccinated neonates in South India were enrolled and cluster-randomised to active or passive surveillance. We assessed the influence of surveillance strategy on TB incidence, case-finding rates and all-cause mortality. Predefined criteria were used to diagnose TB. All deaths were evaluated using a verbal autopsy.Results4382 children contributed to 8164 person-years (py) of follow-up (loss to follow-up 6.9%); 749 children were admitted for TB evaluation (active surveillance: 641; passive surveillance: 108). The TB incidence was 159.2/100 000 py and the overall case-finding rate was 3.19 per 100 py (95% CI 0.82 to 18.1). Whereas, the case-finding rate for definite TB was similar using active or passive case finding, the case-finding rate for probable TB was 1.92/100 py (95% CI 0.83 to 3.78) with active surveillance, significantly higher than 0.3/100 py (95% CI 0.01 to 1.39, p=0.02) with passive surveillance. Compared to passive surveillance, children with active surveillance had decreased risk of dying (OR 0.68, 95%CI 0.47 to 0.98) which was mostly attributable to reduction of death from pneumonia/respiratory infections (OR 0.34, 95%CI 0.14 to 0.80).ConclusionWe provide reliable estimates of TB incidence in South Indian children

Summary Background Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. Methods Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON [QFT]) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. Findings 21 022 (90%) of 23 483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend Interpretation On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. Funding The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.

Tuberculosis remains a global health problem with an enormous burden of disease, estimated at 10.4 million new cases in 2015. To stop the tuberculosis epidemic, it is critical that we interrupt tuberculosis transmission. Further, the interventions required to interrupt tuberculosis transmission must be targeted to high-risk groups and settings. A simple cascade for tuberculosis transmission has been proposed in which (1) a source case of tuberculosis (2) generates infectious particles (3) that survive in the air and (4) are inhaled by a susceptible individual (5) who may become infected and (6) then has the potential to develop tuberculosis. Interventions that target these events will interrupt tuberculosis transmission and accelerate the decline in tuberculosis incidence and mortality. The purpose of this article is to provide a high-level overview of what is known about tuberculosis transmission, using the tuberculosis transmission cascade as a framework, and to set the scene for the articles in this series, which address specific aspects of tuberculosis transmission.

Background: Reliable identification of Mycobacterium tuberculosis infection or tuberculosis (TB) disease in young children is vital to assure adequate preventive and curative treatment. The tuberculin skin test (TST) and IFN[gamma]-release assays may supplement the diagnosis of pediatric TB as cases are typically bacteriologically unconfirmed. However, it is unclear to what extent the performance of TST and QuantiFERON-TB Gold In-Tube (QFT; Cellestis’ IFN[gamma]-release assay test) depends on the demographic, clinical and nutritional characteristics of children in whom they are tested. Methods: During a 2-year prospective observational study of 4382 neonates in Southern India, children with suspected TB were investigated and classified by a standard TB diagnostic algorithm. Results: Clinical TB was diagnosed in 13 of 705 children referred for case verification with suspected TB. TST and QFT had a susceptibility for clinical TB of 31% and 23%, respectively, in this group. Children

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

School-based health education is a promising approach for improving organ donation rates, but little is known about its efficacy among ethnically diverse youth. The impact of a classroom intervention was examined in a multicultural high school population where students' ethnicities were 45% African American, 30% Asian American, and 33% Caucasian (allowing for multiracial choices). A baseline survey was administered to all health classes within two wk prior to intervention. On the intervention day, classes randomly assigned to the intervention group received an educational session, followed by a second survey; in control classes, the second survey was taken before the educational session. At baseline, non-Caucasian ethnicity and male gender were each associated with lower levels of willingness to donate. Following the intervention, students in the intervention group demonstrated a significant increase in knowledge scores (p < 0.001), as well as positive movement of opinion regarding willingness to donate (p < 0.0001). Most importantly, the positive changes in opinion occurred independently of ethnicity and gender, in spite of these both being negative predictors of opinion at baseline. These results demonstrate that even a single classroom exposure can impact knowledge levels, correct misinformation, and effect opinion change on organ donation among an ethnically diverse adolescent population.

Context Support of organ donation among Asian Americans has been limited, but lack of access to information and prevalence of misinformation are 2 barriers that might be counteracted by public education. Objective To solicit advice from 4 Asian American communities on the design of a culturally appropriate educational campaign on organ donation and transplantation. Design and Setting Cross-sectional, multilingual survey administered at community festivals and supermarkets. Participants 201 Asian American respondents. Main Outcome Measures The components of an effective public education outreach campaign on organ donation were defined for 4 Asian American communities. Results Media venues ranked highest for information dissemination on organ donation/transplantation were, in descending order, mainstream television, ethnic newspapers, mainstream newspapers, and ethnic television. Most respondents preferred a spokesperson of Asian American descent, but opinions differed by ethnicity as to whether an effective spokesperson needed to be of the same Asian ethnicity as the respondents. Respondents were further divided by ethnicity on their preference for a locally or nationally well-known spokesperson. The most compelling scenario to promote organ donation was an Asian American waiting for a transplant, followed by an organ donor family or individual, and, last, a transplant recipient. Different advertisements for organ donation appealed to different Asian ethnic groups. Conclusions Community-based research gives communities the opportunity to collaborate with health professionals in designing health education programs that target their own populations. Because key aspects influencing campaign efficacy can vary by ethnicity, these important differences need to be taken into account in outreach planning.

Objectives: Birth certificate and hospital discharge data are relied upon heavily for national surveillance and research on maternal health. Despite the great importance of these data sources, the recording accuracy in these datasets, comparing birth attendant type, has not been evaluated. The study objective was to assess the variation in chart documentation accuracy between certified nurse-midwives (CNMs) and physicians (MDs) for selected maternal variables using birth certificate and hospital discharge data. Methods: Data was obtained on women delivering in 10 Washington State hospitals that had both CNM and MD-attended births in 2000 (n = 2699). Using the hospital medical record as the gold standard of accuracy, the true positive rate (TPR) for selected maternal medical conditions, pregnancy complications, and intrapartum and postpartum events was calculated for CNMs and MDs using birth certificate data, hospital discharge data, and both data sources combined. Results: The magnitude of TPRs for most recorded maternal medical conditions, pregnancy complications, and intrapatum and postpartum events was higher for CNMs than for MDs. TPRs were significantly higher in birth certificate records for pregnancy-induced hypertension, premature rupture of membranes, labor augmentation, induction of labor, and vaginal birth after cesarean (VBAC) for CNM-attended births relative to MDs. Among combined data sources, CNM TPRs were significantly higher for pregnancy-induced hypertension and premature rupture of membranes. Conclusions: CNMs had consistently higher accuracy of recorded maternal medical conditions, pregnancy complications, and intrapartum and postpartum events when compared to MDs for all data sources, with several being statistically significant. Our findings highlight discrepancies between CNM and MD hospital chart documentation, and suggest that epidemiologic researchers consider the issue of measurement error and birth attendant type.

Background: Group B streptococcal disease is the leading cause of neonatal sepsis in the United States. We assessed predictors of compliance with the consensus guidelines for perinatal group B streptococcus disease prevention at two Group Health Cooperative hospitals. Methods: A descriptive and cohort analysis was conducted of failure to comply with the screening-based approach to group B streptococcus prevention among singleton birth pregnancies in two Group Health Cooperative hospitals, September 1, 1996 to December 31, 1997. We studied determinants of failure to screen pregnant women for group B streptococcus at 35 to 37 weeks’ gestation and failure to deliver intrapartum antibiotic prophylaxis to Group B streptococcus-positive women. Results: Nearly 28 percent of 1969 women delivering at two Group Health Cooperative hospitals were not screened appropriately for group B streptococcus. Women who were not screened properly were more likely to be in their teens. A short length of hospital stay before delivery was the strongest predictor of the lack of administration of intrapartum antibiotic prophylaxis to infected multiparas at delivery. Group B streptococcus-positive women without pregnancy complications were less likely to receive intrapartum antibiotic prophylaxis than infected women with complications. Conclusions: The findings of this study suggest that to improve group B streptococcus disease prevention, screening efforts should focus on teenage women, and intrapartum antibiotic prophylaxis delivery efforts should be aimed at low-risk women with precipitous labor. (BIRTH 29:4 December 2002)

Objective: Our purpose was to assess the impact of new consensus guidelines issued by the Centers for Disease Control and Prevention, The American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics to prevent perinatal group B streptococcal disease. Study Design: We performed a descriptive analysis and a before-and-after analysis of implementation of the group B streptococcal disease prevention guidelines among singleton-birth pregnancies in 2 Group Health Cooperative hospitals from October 1, 1995, through December 31, 1997. We studied the speed and completeness of implementation and the effect on pregnancy care practices including intrapartum antibiotic use, test ordering, and maternal and neonatal health. Results: Guideline implementation occurred rapidly. The proportion of term pregnancies screened according to the guideline increased markedly, and overall intrapartum antibiotic use more than doubled. Among group B streptococci–positive women, intrapartum antibiotic prophylaxis increased from 24% before to 74% after guideline implementation. Median duration of treatment before delivery increased from 1.8 to 4.3 hours. The rate of rash did not increase, and there were no cases of anaphylaxis or pseudomembranous colitis. The proportion of infants undergoing evaluation decreased after implementation of the neonatal guidelines; among infants of group B streptococci–negative women, test ordering dropped by almost 40%. Conclusions: Implementation of the new guidelines is feasible and can be accomplished rapidly. The guidelines were associated with increased maternal intrapartum antibiotic use, particularly among women at highest risk, and with a decrease in laboratory use for infants. (Am J Obstet Gynecol 2001;184:603-10.)

The protective efficacy of an oral inactivated whole cell Vibrio cholerae plus recombinant B subunit cholera vaccine was determined against El Tor cholera among Peruvian children and adults (2-65 years old) in a randomized, double-blind manner. Study subjects received 2 doses of vaccine or placebo 2 weeks apart, followed by a booster dose 10 months later. Surveillance for cholera was performed actively, with 2 visits per week to each household, and passively, at a local hospital. Stool samples were collected during diarrhea episodes and were cultured for V. cholerae. A total of 17,799 persons received 2 doses of vaccine or placebo, and 14,997 of these persons received the booster dose. After 2 doses (first surveillance period), V. cholerae biotype O1 was isolated from 17 vaccinees and 16 placebo recipients, demonstrating vaccine efficacy (VE) of -4%. After 3 doses (second surveillance period), V. cholerae O1 was isolated from 13 vaccinees and 32 placebo recipients, demonstrating VE of 61% (95% confidence interval ?CI, 28%-79%). In the second surveillance period, the VE for illness requiring hospitalization was 82% (95% CI, 27%-96%). VE was also higher for persons >15 years old (VE, 72%; 95% CI, 28%-89%).

To assess the safety, immunogenicity, and lot stability of the whole cell/recombinant B subunit cholera vaccine, 2 lots manufactured in June 1991 and February 1992 were tested in January 1995. Two oral doses of vaccine or placebo given 2 weeks apart were given with buffer to 216 Peruvian adults and children. Symptoms were elicited for 3 days after each dose. Serum and plasma specimens obtained from each volunteer before vaccination and 10-14 days after the second dose were tested for vibriocidal and anti-cholera toxin antibodies. The vaccine was well-tolerated. Nearly half of the 100 vaccinees had pre-vaccination vibriocidal titersor = 1:40. Elevated titers were observed in 22% of 37 children 2-5 years of age compared with 66% of 63 vaccinees 6-65 years (P0.001). Aor =2-fold serum vibriocidal response was observed in 55% of 100 vaccinees and 6% of 32 placebo recipients. An elevated pre-vaccination titer (or =1:40) did not change the proportion of vaccinees who responded with aor =2-fold increase in vibriocidal titer (51% versus 59%, difference not significant), but did change the proportion responding with aor =4-fold increase (41% versus 22%; P0.05). The vibriocidal seroconversion rate was lowest in children 2-5 years old despite low pre-vaccination titers. Two-fold or greater serum antitoxic responses in IgA and IgG were observed in90% of the vaccinees;or =4-fold responses were seen in 65-70% of the vaccinees with a 6-8-fold increase over baseline. Plasma specimens were as good as sera for determining anti-toxic antibodies by ELISA, but were less satisfactory for determining vibriocidal antibody titers.

Background Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model’s functionality is demonstrated through a hypothetical vaccine. Methods The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. Results The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and $1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively. Conclusions The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions.

Background: Induction of labor is an increasingly common obstetrical procedure, with approximately 20–34% of women undergoing labor induction in the United States annually. Objective: To determine the extent of labor induction in the absence of standard medical indications and to assess possible associations with maternal and infant characteristics and hospital factors. Methods: We ascertained induction of labor and associated details as part of a medical record validation study of 4541 women with live, singleton births in 2000 in Washington State using medical record, birth certificate, and hospital discharge data. In this analysis, we report findings for the 1473 women (33% of original cohort) whose medical records indicated that their labors were induced. Results: Among women with induced labor, 7.9% had no clinical information providing an indication for the induction, and 6.4% had only “nonstandard” indications recorded. Compared with women delivering in moderate volume hospitals, women who delivered at lower volume (odds ratios [OR] 3.9; 95% confidence intervals [CI] 1.8–8.6) or higher volume hospitals (OR 4.2; 95% CI 2.4–7.2) had significantly increased risk for undocumented indication of labor. Women who had undocumented indication for induction were at significantly decreased risk of giving birth at a teaching hospital and a public nonfederally owned hospital, and were at greater risk to give birth at a private religious hospital. Factors that remained independently associated with nonstandard indication for induction of labor were primiparas (OR 2.4; 95% CI 1.3–4.2); multiparas (OR 4.3; 95% CI 2.5–7.4), pregnancy-induced hypertension (OR 0.2; 95% CI 0.1–0.4), hospital volume ≥2000 births annually (OR 19.9; 95% CI 6.7–58.6), primary (OR 11.7; 95% CI 4.1–33.6), and tertiary level hospital (OR 0.4; 95% CI 0.2–0.7). Conclusions: Our findings suggest that nearly 15% of inductions either were not clinically indicated according to standard protocols or indications were incompletely documented. At minimum, further studies are needed to explore how best to improve documentation of indications of labor because accurately describing, among other things, the process of labor induction, is a basic benchmark of care.

Background:National surveillance estimates reported a troubling 63 percent decline in the rate of vaginal birth after cesarean delivery (VBAC) from 1996 (28.3%) to 2003 (10.6%), with subsequent rising rates of repeat cesarean delivery. The study objective was to examine patterns of documented indications for repeat cesarean delivery in women with and without labor. Methods:We conducted a population-based validation study of 19 nonfederal short-stay hospitals in Washington state. Of the 4,541 women who had live births in 2000, 11 percent (n = 493) had repeat cesarean without labor and 3 percent (n = 138) had repeat cesarean with labor. Incidence of medical conditions and pregnancy complications, patterns of documented indications for repeat cesarean delivery, and perioperative complications in relation to repeat cesarean delivery with and without labor were calculated. Results:Of the 493 women who underwent a repeat cesarean delivery without labor, “elective”(36%) and “maternal request”(18%) were the most common indications. Indications for maternal medical conditions (3.0%) were uncommon. Among the 138 women with repeat cesarean delivery with labor, 60.1 percent had failure to progress, 24.6 percent a non-reassuring fetal heart rate, 8.0 percent cephalopelvic disproportion, and 7.2 percent maternal request during labor. Fetal indications were less common (5.8%). Breech, failed vacuum, abruptio placentae, maternal complications, and failed forceps were all indicated less than 5.0 percent. Women's perioperative complications did not vary significantly between women without and with labor. Regardless of a woman's labor status, nearly 10 percent of women with repeat cesarean delivery had no documented indication as to why a cesarean delivery was performed. Conclusions:“Elective” and “maternal request” were common indications among women undergoing repeat cesarean delivery without labor, and nearly 10 percent of women had undocumented indications for repeat cesarean delivery in their medical record. Improvements in standardization of indication nomenclature and documentation of indication are especially important for understanding falling VBAC rates. Future research should examine how clinicians and women anticipate, discuss, and make decisions about childbirth after a previous cesarean delivery within the context of actual antepartum care. (BIRTH 33:1 March 2006)

Summary While the impact of maternal morbidities and intrapartum procedures is a common topic in perinatal outcomes research, the accuracy of the reporting of these variables in the large administrative databases (birth certificates, hospital discharges) often utilised for such research is largely unknown. We conducted this study to compare maternal diagnoses and procedures listed on birth certificates, hospital discharge data, and birth certificate and hospital discharge data combined, with those documented in a stratified random sample of hospital medical records of 4541 women delivering liveborn infants in Washington State in 2000. We found that birth certificate and hospital discharge data combined had substantially higher true positive fractions (TPF, proportion of women with a positive medical record assessment who were positive using the administrative databases) than did birth certificate data alone for labour induction (86% vs. 52%), cephalopelvic disproportion (83% vs. 35%), abruptio placentae (85% vs. 68%), and forceps-assisted delivery (89% vs. 55%). For procedures available only in hospital discharge data, TPFs were generally high: episiotomy (85%) and third and fourth degree vaginal lacerations (91%). Except for repeat caesarean section without labour (TPF, 81%), delivery procedures available only in birth certificate data had low TPFs, including augmentation (34%), repeat caesarean section with labour (61%), and vaginal birth after caesarean section (62%). Our data suggest that researchers conducting perinatal epidemiological studies should not rely solely on birth certificate data to detect maternal diagnoses and intrapartum procedures accurately.

We sought to estimate the accuracy, relative to maternal medical records, of perinatal risk factors recorded on fetal death certificates. We conducted a validation study of fetal death certificates among women who experienced fetal deaths between 1996 and 2001. The number of previous births, established diabetes, chronic hypertension, maternal fever, performance of autopsy, anencephaly, and Down syndrome had very high accuracy, while placental cord conditions and other chromosomal abnormalities were reported inaccurately. Additional population-based studies are needed to identify strategies to improve fetal death certificate data.

Objective The purpose of this study was to determine the accuracy of live-birth certificates and hospital discharge data that reported of pre-existing maternal medical conditions and complications of pregnancy. Study design We conducted a population-based validation study in 19 non-federal short-stay hospitals in Washington state with a stratified random sample of 4541 women who had live births between January 1, 2000, and December 31, 2000. True- and false-positive fractions were calculated. Results Birth certificate and hospital discharge data combined had substantially higher true-positive fractions than did birth certificate data alone for cardiac disease (54% vs 29%), acute or chronic lung disease (24% vs 10%), gestational diabetes mellitus (93% vs 64%), established diabetes mellitus (97% vs 52%), active genital herpes (77% vs 38%), chronic hypertension (70% vs 47%), pregnancy-induced hypertension (74% vs 49%), renal disease (13% vs 2%), and placenta previa (70% vs 33%). For the 2 medical risk factors that are available only on birth certificates, true-positive fractions were 37% for established genital herpes and 68% for being seropositive for hepatitis B surface antigen. Conclusion In Washington, most medical conditions and complications of pregnancy that affect mothers are substantially underreported on birth certificates, but hospital discharge data are accurate in the reporting of gestational and established diabetes mellitus and placenta previa. Together, birth certificate and hospital discharge data are much superior to birth certificates alone in the reporting of gestational diabetes mellitus, active genital herpes, and chronic hypertension.

To assess knowledge and opinions about the process of human organ donation and transplantation among American teenagers.A culturally sensitive 35-item self-administered survey assessing knowledge, opinions, and family discussion about organ donation and transplantation was conducted with 247 students in 13 separate classrooms encompassing three urban high schools in the same city.More than 50% of the students did not know the correct answers to 13 of the 16 questions on factual knowledge. The sources of information about organ donation and transplantation among students were primarily television and school. African-Americans and Asian-Americans were significantly less likely to want to become organ donors when compared to non-African-Americans and non-Asian-Americans, respectively. Asian-Americans were significantly less likely to have discussed the matter with family members.Accurate, up-to-date, culturally sensitive youth-oriented health education that emphasizes family discussions about organ donation and transplantation is needed.

Background Recommendations from the World Health Organization (WHO) are crucial to inform developing country decisions to use, or not, a new intervention. This article analysed the WHO policy development process to predict its course for a malaria vaccine. Methods The decision-making processes for one malaria intervention and four vaccines were classified through (1) consultations with staff and expert advisors to WHO's Global Malaria Programme (GMP) and Immunization, Vaccines and Biologicals Department (IVB); (2) analysis of the procedures and recommendations of the major policy-making bodies of these groups; (3) interviews with staff of partnerships working toward new vaccine availability; and (4) review and analyses of evidence informing key policy decisions. Case description WHO policy formulation related to use of intermittent preventive treatment in infancy (IPTi) and the following vaccine interventions: Haemophilus influenzae type b conjugate vaccine (Hib), pneumococcal conjugate vaccine (PCV), rotavirus vaccine (RV), and human papillomavirus vaccine (HPV), five interventions which had relatively recently been through systematic WHO policy development processes as currently constituted, was analysed. Required information was categorized in three areas defined by a recent WHO publication on development of guidelines: safety and efficacy in relevant populations, implications for costs and population health, and localization of data to specific epidemiological situations. Discussion and evaluation Data needs for a malaria vaccine include safety; the demonstration of efficacy in a range of epidemiological settings in the context of other malaria prevention interventions; and information on potential rebound in which disease increases subsequent to the intervention. In addition, a malaria vaccine would require attention to additional factors, such as costs and cost-effectiveness, supply and demand, impact of use on other interventions, and distribution issues. Conclusions Although policy issues may be more complex for future vaccines, the lead-time between the date of product regulatory approval and a recommendation for its use in developing countries is decreasing. This study presents approaches to define in advance core data needs to support evidence-based decisions, to further decrease this lead-time, accelerating the availability of a malaria vaccine. Specific policy areas for which information should be collected are defined, including studying its use within the context of other malaria interventions.