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Background Group B Streptococcus (GBS) can cause invasive disease (iGBS) in young infants, typically presenting as sepsis or meningitis, and is also associated with stillbirth and preterm birth. GBS vaccines are under development, but their potential health impact and cost-effectiveness have not been assessed globally. Methods and findings We assessed the health impact and value (using net monetary benefit (NMB), which measures both health and economic effects of vaccination into monetary units) of GBS maternal vaccination in an annual cohort of 140 million pregnant women across 183 countries in 2020. Our analysis uses a decision tree model, incorporating risks of GBS-related health outcomes from an existing Bayesian disease burden model. We extrapolated country-specific GBS-related healthcare costs using data from a previous systematic review and calculated quality-adjusted life years (QALYs) lost due to infant mortality and long-term disability. We assumed 80% vaccine efficacy against iGBS and stillbirth, following the WHO Preferred Product Characteristics, and coverage based on the proportion of pregnant women receiving at least 4 antenatal visits. One dose was assumed to cost $50 in high-income countries, $15 in upper-middle income countries, and $3.50 in low-/lower-middle-income countries. We estimated NMB using alternative normative assumptions that may be adopted by policymakers. Vaccinating pregnant women could avert 127,000 (95% uncertainty range 63,300 to 248,000) early-onset and 87,300 (38,100 to 209,000) late-onset infant iGBS cases, 31,100 deaths (14,400 to 66,400), 17,900 (6,380 to 49,900) cases of moderate and severe neurodevelopmental impairment, and 23,000 (10,000 to 56,400) stillbirths. A vaccine effective against GBS-associated prematurity might also avert 185,000 (13,500 to 407,000) preterm births. Globally, a 1-dose vaccine programme could cost $1.7 billion but save $385 million in healthcare costs. Estimated global NMB ranged from $1.1 billion ($-0.2 to 3.8 billion) under the least favourable normative assumptions to $17 billion ($9.1 to 31 billion) under the most favourable normative assumptions. The main limitation of our analysis was the scarcity of data to inform some of the model parameters such as those governing health-related quality of life and long-term costs from disability, and how these parameters may vary across country contexts. Conclusions In this study, we found that maternal GBS vaccination could have a large impact on infant morbidity and mortality. Globally, a GBS maternal vaccine at reasonable prices is likely to be a cost-effective intervention., Author(s): Simon R. Procter 1,2,*, Bronner P. Gonçalves 1,2, Proma Paul 1,2, Jaya Chandna 1,2, Farah Seedat 1,2, Artemis Koukounari 1,2, Raymond Hutubessy 3, Caroline Trotter 4, Joy E. Lawn [...]

Background Maternal colonization by the bacterium Group B streptococcus (GBS) increases risk of preterm birth, a condition that has an important impact on the health of children. However, research studies that quantify the effect of GBS colonization on preterm birth have reported variable estimates of the effect measure. Methods We performed a simulated cohort study of pregnant women to assess how timing of exposure (GBS colonization) assessment might influence results of studies that address this question. We used published data on longitudinal maternal GBS colonization and on the distribution of preterm births by gestational age to inform parameters used in the simulations. Results Assuming that the probability of preterm birth is higher during weeks when pregnant women are colonized by GBS, our results suggest that studies that assess exposure status early during pregnancy are more likely to estimate an association between GBS colonization and preterm birth that is closer to the null, compared with studies that assess exposure either at birth or during gestational weeks matched to preterm births. In sensitivity analyses assuming different colonization acquisition rates and diagnostic sensitivities, we observed similar results. Conclusions Accurate quantification of the effect of maternal GBS colonization on the risk of preterm birth is necessary to understand the full health burden linked to this bacterium. In this study, we investigated one possible explanation, related to the timing of exposure assessment, for the variable findings of previous observational studies. Our findings will inform future research on this question. [ABSTRACT FROM AUTHOR]

Objective To assess human papillomavirus (HPV) vaccination coverage after demonstration projects conducted in India, Peru, Uganda and Viet Nam by PATH and national governments and to explore the reasons for vaccine acceptance or refusal. Methods Vaccines were delivered through schools or health centres or in combination with other health interventions, and either monthly or through campaigns at fixed time points. Using a two-stage cluster sample design, the authors selected households in demonstration project areas and interviewed over 7000 parents or guardians of adolescent girls to assess coverage and acceptability. They defined full vaccination as the receipt of all three vaccine doses and used an open-ended question to explore acceptability. Findings Vaccination coverage in school-based programmes was 82.6% (95% confidence interval, CI: 79.3-85.6) in Peru, 88.9% (95% CI: 84.7-92.4) in 2009 in Uganda and 96.1% (95% CI: 93.0-97.8) in 2009 in Viet Nam. In India, a campaign approach achieved 77.2% (95% CI: 72.4-81.6) to 87.8% (95% CI: 84.3-91.3) coverage, whereas monthly delivery achieved 68.4% (95% CI: 63.4-73.4) to 83.3% (95% CI: 79.3-87.3) coverage. More than two thirds of respondents gave as reasons for accepting the HPV vaccine that: (i) it protects against cervical cancer; (ii) it prevents disease, or (iii) vaccines are good. Refusal was more often driven by programmatic considerations (e.g. school absenteeism) than by opposition to the vaccine. Conclusion High coverage with HPV vaccine among young adolescent girls was achieved through various delivery strategies in the developing countries studied. Reinforcing positive motivators for vaccine acceptance is likely to facilitate uptake. Objectif Evaluer la couverture vaccinale anti-papillomavirus humain (VPH) suite a des projets pilotes menes en Inde, au Perou, en Ouganda et au Viet Nam par le PATH et par les gouvernements nationaux, et etudier les raisons de l'acceptation ou du refus de la vaccination. Methodes Les vaccins etaient delivres par des ecoles ou des centres de soins ou conjointement a d'autres interventions sanitaires, et de facon mensuelle ou par des campagnes ponctuelles. En utilisant un echantillonnage en grappes a deux etapes, les auteurs ont selectionne des menages dans des zones de projet pilote et ont interroge plus de 7 000 parents ou tuteurs d'adolescentes afin d'evaluer la couverture et l'acceptabilite du vaccin. Ils ont defini la vaccination complete comme etant la prise de l'ensemble des trois doses vaccinales et ont eu recours a des questions ouvertes pour etudier l'acceptabilite. Resultats La couverture vaccinale, pour les programmes en milieu scolaire, etait de 82,6% (intervalle de confiance de 95%, IC: 79,3-85,6) au Perou, de 88,9% (IC de 95%: 84,7-92,4) en 2009 en Ouganda et de 96,1% (IC de 95%: 93.0-97,8) en 2009 au Viet Nam. En Inde, une approche de type campagne a permis de realiser une couverture allant de 77,2% (IC de 95%: 72,4-81,6) a 87,8% (IC de 95%: 84,3-91,3), alors que la delivrance mensuelle a permis de realiser une couverture allant de 68,4% (IC de 95%: 63,4-73,4) a 83,3% (IC de 95%: 79,3-87,3). Plus des deux tiers des personnes interrogees ont justifie l'acceptation du vaccin VPH pour les raisons suivantes: (i) il protege contre le cancer du col de l'uterus; (ii) il empeche la maladie, ou (iii) les vaccins sont bons. Le refus etait plus souvent justifie par des considerations liees au programme (par ex. l'absenteisme scolaire) que par une opposition au vaccin. Conclusion Une couverture elevee du vaccin VPH parmi les jeunes filles a ete obtenue par differentes strategies de delivrance dans les pays en voie de developpement a l'etude. Le renforcement des elements de motivation positifs pour l'acceptation du vaccin est susceptible d'en faciliter la prise. Objetivo Evaluar la cobertura de la vacunacion del virus del papiloma humano (VPH) despues de los proyectos de demostracion Ilevados a cabo por PATH y los gobiernos nacionales en la India, Peru, Uganda y Vietnam, asi como examinar las razones de aceptacion o rechazo de la vacuna. Metodos Las vacunas se suministraron en colegios o centros de salud, o en combinacion con otras intervenciones sanitarias, mensualmente o por medio de campanas realizadas en momentos especificos. Mediante el uso de un diseno de muestreo por conglomerados de dos fases, los autores seleccionaron hogares en areas del proyecto de demostracion y entrevistaron a mas de 7000 padres o tutores de ninas adolescentes para evaluar su cobertura y aceptabilidad. Definieron la vacunacion completa como el momento en el que se habian recibido las tres dosis de vacuna y utilizaron una pregunta de interpretacion abierta para examinar la aceptabilidad. Resultados La cobertura de la vacunacion en programas realizados en colegios fue del 82,6% (Intervalo de confianza del 95%, IC: 79,3-85,6) en Peru, 88,9% (IC del 95%: 84,7-92,4) en Uganda, en el ano 2009, y del 96,1% (IC del 95%: 93,0-97,8) en Vietnam, tambien en el ano 2009. En la India, un enfoque de campana consiguio del 77,2% (IC del 95%: 72,4-81,6) al 87,8% (95% IC: 84,3-91,3) de cobertura, mientras que el suministro mensual consiguio una cobertura del 68,4% (IC del 95%: 63,4-73,4) al 83,3% (95% IC: 79,3-87,3). Mas de dos tercios de los participantes indicaron como razones para la aceptacion de la vacuna dei VPH que: (i) protege del cancer de cuello de utero; (ii) previene la enfermedad o (iii) las vacunas son buenas. El rechazo fue mas habitual en base a consideraciones programaticas (p. ej., absentismo escolar) que por el rechazo a la vacuna. Conclusion Con la vacuna del VPH se consiguio una alta cobertura entre chicas adolescentes jovenes mediante diversas estrategias de su ministro en los paises en desarrollo estudiados. Es probable que el refuerzo de las motivaciones positivas para la aceptacion de facilite su aceptacion., Introduction The global burden of cervical cancer is large and is increasing and it disproportionately affects low-resource countries. (1) In 2008 there were approximately 529 000 new cases and over [...]

Background Invasive group B Streptococcus disease (iGBS) in infancy, including meningitis or sepsis, carries a high risk of mortality and neurodevelopmental impairment (NDI). We present data on iGBS from 2 decades of surveillance in Manhiça, Mozambique, with a focus on NDI. Methods Morbidity surveillance databases in a rural Mozambican district hospital were screened for iGBS cases. From February 2020 to March 2021, surviving iGBS patients (n = 39) plus age- and sex-matched children without iGBS (n = 119) were assessed for neurocognitive development, vision, and hearing. The role of GBS in stillbirths and infant deaths was investigated using minimally invasive tissue sampling (MITS). Results Ninety iGBS cases were included, with most children being <3 months of age (85/90). The in-hospital case fatality rate was 14.4% (13/90), increasing to 17.8% (3 additional deaths) when considering mortality during the 6 months postdiagnosis. Fifty percent of the iGBS exposed infants and 10% of those unexposed showed any NDI. Surviving GBS conferred a 11-fold increased adjusted odds of moderate/severe NDI (odds ratio, 2.8 [95% confidence interval,.92–129.74]; P  = .06) in children aged 0–5 years. For older children (6–18 years), no differences in NDI were found between exposed and unexposed. Motor domain was the most affected among young GBS survivors. Three stillbirths and 4 early neonatal deaths (of the 179 MITS performed) were attributed to iGBS. Conclusions In absence of preventive strategies, such as intrapartum antibiotics, iGBS remains a significant cause of perinatal and infant disease and death. GBS also causes major longer-term neurodevelopmental sequelae, altogether justifying the need for maternal GBS vaccination strategies to increase perinatal and infant survival. [ABSTRACT FROM AUTHOR]

Background This study is part of a multicountry matched-cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI) of children exposed to invasive group B Streptococcus (iGBS). The specific objective of this paper is to compare NDI across domains of iGBS survivors with a matched non iGBS group in our population. Methods Survivors of iGBS in a South Indian hospital were identified and recruited between January 2020 and April 2021. Cases were compared with age- and gender-matched non iGBS children. Participants were assessed using Bayley Scales of Infant and Toddler Development–3rd edition (BSID-III), Wechsler Preschool and Primary Scale of Intelligence–4th edition (WPPSI-IV), Wechsler Intelligence Scale for Children–5th edition (WISC-V), Child Behavior Checklist (CBCL), and Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2), depending on age. Results Our cohort comprised 35 GBS-exposed and 65 matched non iGBS children, aged 1–14 years. The iGBS-exposed group had 17 (48.6%) children with impairment in ≥1 domain compared to 25 (38%) in the non iGBS group (unadjusted OR, 1.51; 95% CI,.65–3.46), 9 (26%) children with "multi-domain impairment" compared to 10 (15.4%) in the non iGBS group (unadjusted OR, 1.90; 95% CI,.69–5.24), and 1 (2.9%) child with moderate to severe impairment compared to 3 (4.6%) in the non iGBS group (unadjusted OR,.60; 95% CI,.06–6.07). In the iGBS group, more children had motor impairments compared with the non iGBS group (unadjusted OR, 10.7; 95% CI, 1.19–95.69; P  = .034). Conclusions Children with iGBS seem at higher risk of developing motor impairments compared with a non iGBS group. [ABSTRACT FROM AUTHOR]

The global burden of Group B Streptococcus (GBS) was estimated for 2015 prompting inclusion of GBS as a priority in the Global Meningitis Roadmap. New estimates for the year 2020 and a WHO report analysing the full value of GBS maternal vaccines has been launched to advance evidence based decision making for multiple stakeholders. In this first of a 10-article supplement, we discuss the following (1) gaps in evidence and action, (2) new evidence in this supplement, and (3) what actions can be taken now and key research gaps ahead. We call for investment in the research pipeline, notably description, development, and delivery, in order to accelerate progress and address the large burden of GBS for every family in every country. [ABSTRACT FROM AUTHOR]

Neonatal invasive disease caused by Group B Streptococcus (GBS) is responsible for much acute mortality and long-term morbidity. To guide development of better prevention strategies, including maternal vaccines that protect neonates against GBS, it is necessary to estimate the burden of this condition globally and in different regions. Here, we present a Bayesian model that estimates country-specific invasive GBS (iGBS) disease incidence in children aged 0 to 6 days. The model combines different types of epidemiological data, each of which has its own limitations: GBS colonization prevalence in pregnant women, risk of iGBS disease in children born to GBS-colonized mothers and direct estimates of iGBS disease incidence where available. In our analysis, we present country-specific maternal GBS colonization prevalence after adjustment for GBS detection assay used in epidemiological studies. We then integrate these results with other epidemiological data and estimate country-level incidence of iGBS disease including in countries with no studies that directly estimate incidence. We are able to simultaneously estimate two key epidemiological quantities: the country-specific incidence of early-onset iGBS disease, and the risk of iGBS disease in babies born to GBS-colonized women. Overall, we believe our method will contribute to a more comprehensive quantification of the global burden of this disease, inform cost-effectiveness assessments of potential maternal GBS vaccines and identify key areas where data are necessary. Author summary: Invasive disease caused by Group B Streptococcus (GBS) in young infants continues to be a major public health problem in both developed and developing countries. However, data on the incidence of this infection during the first week of life are only available for a small number of countries, which has complicated the quantification of the burden of this disease globally. In this paper, we develop a Bayesian framework to estimate the incidence of invasive GBS infection that combines data from multiple types of epidemiological studies, with adjustment for relevant factors such as diagnostic methods used in the studies. We present estimates from a series of models, and our results highlight the potential weaknesses of different types of studies and the importance to consider the entire evidence when estimating global burden of invasive neonatal infections. We believe this model is a step toward better quantification of the number of cases in different regions. [ABSTRACT FROM AUTHOR]

• Most comprehensive review of Group B Streptococcal serotypes through 2018. • First systematic review of Group B Streptococcal strain type and protein data. • Theoretically candidate vaccines may protect against 93-99% disease-causing strains. • More studies on GBS strains in low- and middle-income countries are needed. 21 million pregnant women worldwide (18%) are estimated to carry Group B Streptococcus (GBS), which is a risk for invasive disease in newborns, pregnant women, and stillbirths. Adults ≥ 60 years or with underlying health conditions are also vulnerable to invasive GBS disease. We undertook systematic reviews on GBS organism characteristics including: capsular polysaccharide (serotype), sequence type (multi-locus sequence types (MLST)), and virulence proteins. We synthesised data by at-risk populations, to inform vaccine development. We conducted systematic reviews and meta -analyses to estimate proportions of GBS serotypes for at risk populations: maternal colonisation, invasive disease in pregnant women, stillbirths, infants 0–90 days age, and older adults (≥60 years). We considered regional variation and time trends (2001–2018). For these at-risk population groups, we summarised reported MLST and surface proteins. Based on 198 studies (29247isolates), 93–99% of GBS isolates were serotypes Ia, Ib, II, III, IV and V. Regional variation is likely, but data gaps are apparent, even for maternal colonisation which has most data. Serotype III dominates for infant invasive disease (60%) and GBS-associated stillbirths (41%). ST17 accounted for a high proportion of infant invasive disease (41%; 95%CI: 35–47) and was found almost exclusively in serotype III strains, less present in maternal colonisation (9%; 95%CI:6–13),(4%; 95%CI:0–11) infant colonisation, and adult invasive disease (4%, 95%CI:2–6). Percentages of strains with at least one of alp 1, alp2/3, alpha C or Rib surface protein targets were 87% of maternal colonisation, 97% infant colonisation, 93% infant disease and 99% adult invasive disease. At least one of three pilus islands proteins were reported in all strains. A hexavalent vaccine (serotypes Ia, Ib, II, III, IV and V) might provide comprehensive cover for all at-risk populations. Surveillance of circulating, disease-causing target proteins is useful to inform vaccines not targeting capsular polysaccharide. Addressing data gaps especially by world region and some at-risk populations (notably stillbirths) is fundamental to evidence-based decision-making during vaccine design. [ABSTRACT FROM AUTHOR]

Background: In the current information age, the use of data has become essential for decision making in public health at the local, national, and global level. Despite a global commitment to the use and sharing of public health data, this can be challenging in reality. No systematic framework or global operational guidelines have been created for data sharing in public health. Barriers at different levels have limited data sharing but have only been anecdotally discussed or in the context of specific case studies. Incomplete systematic evidence on the scope and variety of these barriers has limited opportunities to maximize the value and use of public health data for science and policy. Methods: We conducted a systematic literature review of potential barriers to public health data sharing. Documents that described barriers to sharing of routinely collected public health data were eligible for inclusion and reviewed independently by a team of experts. We grouped identified barriers in a taxonomy for a focused international dialogue on solutions. Results: Twenty potential barriers were identified and classified in six categories: technical, motivational, economic, political, legal and ethical. The first three categories are deeply rooted in well-known challenges of health information systems for which structural solutions have yet to be found; the last three have solutions that lie in an international dialogue aimed at generating consensus on policies and instruments for data sharing. Conclusions: The simultaneous effect of multiple interacting barriers ranging from technical to intangible issues has greatly complicated advances in public health data sharing. A systematic framework of barriers to data sharing in public health will be essential to accelerate the use of valuable information for the global good. [ABSTRACT FROM AUTHOR]

Due to high cervical cancer rates and limited research on human papillomavirus (HPV) vaccine acceptability in India, the research team examined parental attitudes toward HPV vaccines. Thirty-six interviews with parents were conducted to assess sexually transmitted infection (STI)-related knowledge and HPV-specific vaccine awareness and acceptability. Despite limited knowledge, parents had positive views toward HPV vaccines. Common barriers included concerns about side effects, vaccine cost, and missing work to receive the vaccine. Parents were strongly influenced by health care providers’ recommendations. Our findings suggest that addressing parental concerns, health worker training and polices, and efforts to minimize cost will be central to successful HPV vaccine implementation. [ABSTRACT FROM PUBLISHER]

Background Vaginal self-sampling with HPV-DNA tests is a promising primary screening method for cervical cancer. However, women's experiences, concerns and the acceptability of such tests in low-resource settings remain unknown. Methods In India, Nicaragua, and Uganda, a mixed-method design was used to collect data from surveys (N = 3,863), qualitative interviews (N = 72; 20 providers and 52 women) and focus groups (N = 30 women) on women's and providers' experiences with self-sampling, women's opinions of sampling at home, and their future needs. Results Among surveyed women, 90% provided a self- collected sample. Of these, 75% reported it was easy, although 52% were initially concerned about hurting themselves and 24% were worried about not getting a good sample. Most surveyed women preferred self-sampling (78%). However it was not clear if they responded to the privacy of self-sampling or the convenience of avoiding a pelvic examination, or both. In follow-up interviews, most women reported that they didn't mind self-sampling, but many preferred to have a provider collect the vaginal sample. Most women also preferred clinic-based screening (as opposed to homebased self-sampling), because the sample could be collected by a provider, women could receive treatment if needed, and the clinic was sanitary and provided privacy. Self-sampling acceptability was higher when providers prepared women through education, allowed women to examine the collection brush, and were present during the self-collection process. Among survey respondents, aids that would facilitate self-sampling in the future were: staff help (53%), additional images in the illustrated instructions (31%), and a chance to practice beforehand with a doll/model (26%). Conclusion Self-and vaginal-sampling are widely acceptable among women in low-resource settings. Providers have a unique opportunity to educate and prepare women for self-sampling and be flexible in accommodating women's preference for self-sampling. [ABSTRACT FROM AUTHOR]

Cervical cancer is preventable but continues to cause the deaths of more than 270,000 women worldwide each year, most of them in developing countries where programs to detect and treat precancerous lesions are not affordable or available. Studies have demonstrated that screening by visual inspection of the cervix using acetic acid (VIA) is a simple, affordable, and sensitive test that can identify precancerous changes of the cervix so that treatment such as cryotherapy can be provided. Government partners implemented screening and treatment using VIA and cryotherapy at demonstration sites in Peru, Uganda, and Vietnam. Evaluations were conducted in the three countries to explore the barriers and facilitating factors for the use of services and for incorporation of screen-and-treat programs using VIA and cryotherapy into routine services. Results showed that use of VIA and cryotherapy in these settings is a feasible approach to providing cervical cancer prevention services. Activities that can help ensure successful programs include mobilizing and educating communities, organizing services to meet women's schedules and needs, and strengthening systems to track clients for follow-up. Sustainability also depends on having an adequate number of trained providers and reducing staff turnover. Although some challenges were found across all sites, others varied from country to country, suggesting that careful assessments before beginning new secondary prevention programs will optimize the probability of success. [ABSTRACT FROM AUTHOR]

Abstract: This study investigates the effect of communication strategies on human papillomavirus (HPV) vaccine uptake in HPV vaccine demonstration projects in Uganda and Vietnam. Secondary analysis was conducted on data from surveys of a representative sample of parents and guardians of girls eligible for HPV vaccine, measuring three-dose coverage achieved in demonstration projects in 2008–2010. Univariate and multivariate logistic regression analysis calculated the unadjusted and adjusted odds of receiving at least one dose of HPV vaccine depending on exposure to community influencers; information, education, and communication (IEC) channels; and demographic factors. This study found that exposure to community influencers was associated with HPV vaccine uptake in a multivariate model controlling for other factors. Exposure to non-interactive IEC channels was only marginally associated with HPV vaccine uptake. These results underscore the need of HPV vaccine programs in low- and middle-income countries to involve and utilize key community influencers and stakeholders to maximize HPV vaccine uptake. [Copyright &y& Elsevier]

Background: When addressing the urgent task of improving vaccine supply chains, especially to accommodate the introduction of new vaccines, there is often a heavy emphasis on stationary storage. Currently, donations to vaccine supply chains occur largely in the form of storage equipment. Methods: This study utilized a HERMES-generated detailed, dynamic, discrete event simulation model of the Niger vaccine supply chain to compare the impacts on vaccine availability of adding stationary cold storage versus transport capacity at different levels and to determine whether adding stationary storage capacity alone would be enough to relieve potential bottlenecks when pneumococcal and rotavirus vaccines are introduced by 2015. Results: Relieving regional level storage bottlenecks increased vaccine availability (by 4%) more than relieving storage bottlenecks at the district (1% increase), central (no change), and clinic (no change) levels alone. Increasing transport frequency (or capacity) yielded far greater gains (e.g., 15% increase in vaccine availability when doubling transport frequency to the district level and 18% when tripling). In fact, relieving all stationary storage constraints could only increase vaccine availability by 11%, whereas doubling the transport frequency throughout the system led to a 26% increase and tripling the frequency led to a 30% increase. Increasing transport frequency also reduced the amount of stationary storage space needed in the supply chain. The supply chain required an additional 61,269L of storage to relieve constraints with the current transport frequency, 55,255L with transport frequency doubled, and 51,791L with transport frequency tripled. Conclusions: When evaluating vaccine supply chains, it is important to understand the interplay between stationary storage and transport. The HERMES-generated dynamic simulation model showed how augmenting transport can result in greater gains than only augmenting stationary storage and can reduce stationary storage needs. [ABSTRACT FROM AUTHOR]

Background: While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness. Methods and Findings: A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity = 78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures. Conclusions: We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality. [ABSTRACT FROM AUTHOR]

Objective: The aim of this research was to determine correlates of prevalent cervicovaginal human papillomavirus (HPV) infection in perimenopausal women. Methods: A total of 178 women, ages 40–60, were recruited from four clinics in the metropolitan area of Baltimore, Maryland. A self-collected cervicovaginal specimen and questionnaire were completed following enrollment and consent. HPV was detected by L1 consensus polymerase chain reaction (PCR) and genotyped using a prototype line blot assay. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) from Poisson regression models with robust variance identified correlates of prevalent HPV infection. Results: Prevalence of any HPV genotype at baseline among 172 women with complete data was 20% (6% for high-risk HPV). HPV prevalence was higher among single compared to married women (aPR = 4.3 [95% CI: 2.0, 9.5]), and among women with ≥2 sex partners in the last six months compared to women who reported none (aPR = 4.9 [1.7, 13.9]) after adjustment for confounders. Menopausal stage was also associated with HPV detection, with increased prevalence among perimenopausal compared to premenopausal women (aPR 2.3 [1.1, 5.1]), after adjustment for confounders. Age was moderately correlated with menopausal staging ( r = 0.57). Conclusions: Our observations suggest the independent associations of sexual behavior and hormones on prevalent HPV in perimenopausal women. Age was not a good surrogate for menopausal stage, as it was only moderately correlated with menopausal stage. [ABSTRACT FROM AUTHOR]

The article offers a study which examines the comparability of Hybrid Capture 2 and a polymerase chain reaction (PCR) based method for detection of high-risk human papillomavirus (HPV). The study determines whether participation rates improved with home-based against clinic-based self collection. It depicts that the combination of improved screening coverage and a high single test sensitivity by HPV deoxyribonucleic acid (DNA) testing of home-based self-collected swabs have greater impact.

Background: Vaginal self-sampling with HPV-DNA tests is a promising primary screening method for cervical cancer. However, women's experiences, concerns and the acceptability of such tests in low-resource settings remain unknown.Methods: In India, Nicaragua, and Uganda, a mixed-method design was used to collect data from surveys (N = 3,863), qualitative interviews (N = 72; 20 providers and 52 women) and focus groups (N = 30 women) on women's and providers' experiences with self-sampling, women's opinions of sampling at home, and their future needs.Results: Among surveyed women, 90% provided a self- collected sample. Of these, 75% reported it was easy, although 52% were initially concerned about hurting themselves and 24% were worried about not getting a good sample. Most surveyed women preferred self-sampling (78%). However it was not clear if they responded to the privacy of self-sampling or the convenience of avoiding a pelvic examination, or both. In follow-up interviews, most women reported that they didn't mind self-sampling, but many preferred to have a provider collect the vaginal sample. Most women also preferred clinic-based screening (as opposed to home-based self-sampling), because the sample could be collected by a provider, women could receive treatment if needed, and the clinic was sanitary and provided privacy. Self-sampling acceptability was higher when providers prepared women through education, allowed women to examine the collection brush, and were present during the self-collection process. Among survey respondents, aids that would facilitate self-sampling in the future were: staff help (53%), additional images in the illustrated instructions (31%), and a chance to practice beforehand with a doll/model (26%).Conclusion: Self-and vaginal-sampling are widely acceptable among women in low-resource settings. Providers have a unique opportunity to educate and prepare women for self-sampling and be flexible in accommodating women's preference for self-sampling. [ABSTRACT FROM AUTHOR]

Routine maternal immunisation against influenza and pertussis are recommended by the WHO to protect mother and child, and new vaccines are under development. Introducing maternal vaccines into national programmes requires an understanding of vaccine delivery costs – particularly in low resource settings. We searched Medline, Embase, Econlit, and Global Health for studies reporting costs of delivering vaccination during pregnancy but excluded studies that did not separate the vaccine purchase price. Extracted costs were inflated and converted to 2018 US dollars. Sixteen studies were included, of which two used primary data to estimate vaccine delivery costs. Costs per dose ranged from $0.55 to $0.64 in low-income countries, from $1.25 to $6.55 for middle-income countries, and from $5.76 to $39.87 in high-income countries. More research is needed on the costs of delivering maternal immunisation during pregnancy, and of integrating vaccine delivery into existing programmes of antenatal care especially in low and middle-income countries. [ABSTRACT FROM AUTHOR]

Background care HPV is a new, lower-cost DNA test for human papillomavirus (HPV). There are limited analytic comparisons of care HPV against a referent HPV DNA test like Hybrid Capture 2 (HC2). Objective To assess the test agreement between care HPV and HC2 on self- and clinician-collected specimens. Study design In a population of 7541 women living in rural China, women provided a self-collected (sc) and two clinician-collected (cc) specimens and underwent visual inspection after acetic acid (VIA). The sc specimen and one cc specimen were tested by care HPV and HC2; a random subset of specimens was tested for HPV genotypes. Results The percent positive on cc specimens and sc specimens was 14.69% and 14.97% for care HPV, respectively, and 15.05% and 18.53% for HC2, respectively; HC2 testing of sc specimens was more likely to test positive than other combinations of tests and specimens ( p < 0.0001 for all comparisons). The agreement between different tests on the same specimens (kappa = 0.787 and 0.691 for cc and sc specimens, respectively) was better than the same test on different specimens (kappa = 0.653 and 0.649 for HC2 and care HPV, respectively). Disagreement between the same test on different specimens increased with increasing participant age ( p trend = 0.0001 for HC2 and 0.002 for care HPV). HC2-positive/ care HPV-negative specimens were more likely to test positive for non-carcinogenic HPV genotype than test HPV negative whereas the converse was true for HC2-negative/ care HPV-positive specimens. Discussion The agreement for HPV DNA detection between care HPV and HC2 was good to very good. [ABSTRACT FROM AUTHOR]

The ATM protein kinase regulates the response of the cell to DNA damage by associating with and then phosphorylating proteins involved in cell cycle checkpoints and DNA repair. Here, we report on deletion studies designed to identify protein domains required for ATM to phosphorylate target proteins and to control cell survival following exposure to ionizing radiation. Deletion studies demonstrated that amino acids 1–150 of ATM were required for the ATM protein to regulate cellular radiosensitivity. Additional deletions and point mutations indicated that this domain extended from Amino acids 81–106 of ATM, with amino acid substitutions located between amino acids 91 and 97 inactivating the functional activity of ATM. When ATM with mutations in this region (termed ATM90) was expressed in AT cells, it was unable to restore normal radiosensitivity to the cells. However, ATM90 retained normal kinase activity and was autophosphorylated on serine 1981 following exposure to DNA damage. Furthermore, wild-type ATM displayed DNA-damage induced association with p53, brca1, and LKB1 in vivo, whereas ATM90 failed to form productive complexes with these target proteins either in vivo or in vitro. Furthermore, ATM90 did not phosphorylate p53 in vivo and did not form nuclear foci in response to ionizing radiation. We propose that amino acids 91–97 of ATM contain a protein interaction domain required for the DNA damage-induced association between ATM and its target proteins, including the brca1, pK3, and LKB1 proteins. Furthermore, this domain of ATM is required for ATM to form nuclear foci following exposure to ionizing radiation. [ABSTRACT FROM AUTHOR]

Introduction: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa., Methods: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data., Results: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10)., Conclusion: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Group B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets., Methods: We collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates., Findings: Data from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9-21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100-455 000) early-onset and 162 200 (70 200-394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800-187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500-125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600-96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500-66 200) maternal iGBS cases and 46 200 (20 300-111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births., Interpretation: Our analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests The Department of Clinical Epidemiology of Aarhus University receives funding from private and public institutions in the form of institutional research grants to (and administered by) Aarhus University; none of these grants has any relation to the present study. SAM declares funding from Astrazeneca, the Bill & Melinda Gates Foundation, GlaxoSmithKline, Minervax, Novavax, Pfizer, and the South Africa Medical Research Council; in particular, SAM delares funding to his institution from Pfizer for epidemiology studies on group B streptococcus (GBS) and a clinical trial on the GBS vaccine, and from the Bill & Melinda Gates Foundation on GBS epidemiology. FS declares employment by the UK National Screening Committee, which developed the policy recommendation for maternal GBS screening. CT declares a consulting fee from WHO for drafting a report on the Full Value of Vaccine Assessment for GBS vaccines, which is related to the current manuscript. RL declares participation on an advisory board for Janssen and Pfizer; payment for lectures from Reckitt; and grants to Fundación INFANT from the Bill & Melinda Gates Foundation and PATH. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Data are limited regarding long-term consequences of invasive GBS (iGBS) disease in early infancy, especially from low- and middle-income countries (LMIC) where most cases occur. We aimed to estimate risk of neurodevelopmental impairment (NDI) in children with a history of iGBS disease., Methods: A multi-country matched cohort study was undertaken in South Africa, India, Mozambique, Kenya, and Argentina from October 2019 to April 2021. The exposure of interest was defined as a history of iGBS disease (sepsis or meningitis) before 90 days of age, amongst children now aged 1·5-18 years. Age and sex-matched, children without history of GBS were also recruited. Age-appropriate, culturally-adapted assessments were used to define NDI across multiple domains (cognitive, motor, hearing, vision, emotional-behaviour, growth). Pooled NDI risk was meta-analysed across sites. Association of iGBS exposure and NDI outcome was estimated using modified Poisson regression with robust variance estimator., Findings: Amongst 138 iGBS survivors and 390 non-iGBS children, 38·1% (95% confidence interval [CI]: 30·0% - 46·6%) of iGBS children had any NDI, compared to 21·7% (95% CI: 17·7% - 26·0%) of non- iGBS children, with notable between-site heterogeneity. Risk of moderate/severe NDI was 15·0% (95% CI: 3·4% - 30·8%) among GBS-meningitis, 5·6% (95% CI: 1·5% - 13·7%) for GBS-sepsis survivors. The adjusted risk ratio (aRR) for moderate/severe NDI among iGBS survivors was 1.27 (95% CI: 0.65, 2.45), when compared to non-GBS children. Mild impairment was more frequent in iGBS (27.6% (95% CI: 20.3 - 35.5%)) compared to non-GBS children (12.9% (95% CI: 9.7% - 16.4%)). The risk of emotional-behavioural problems was similar irrespective of iGBS exposure (aRR=0.98 (95% CI: 0.55, 1.77))., Interpretation: Our findings suggest that iGBS disease is on average associated with a higher risk of moderate/severe NDI, however substantial variation in risk was observed between sites and data are consistent with a wide range of values. Our study underlines the importance of long-term follow-up for at-risk neonates and more feasible, standardised assessments to facilitate diagnosis in research and clinical practice., Funding: This work was supported by a grant (INV-009018) from the Bill & Melinda Gates Foundation to the London School of Hygiene &Tropical Medicine., Competing Interests: SRP reports additional finding from Bill & Melinda Gates Foundation on Covid-19 related projects.  ZD and SL report subawards from the London School of Hygiene & Tropical Medicine (LSHTM) to the Wits Health Consortium. SS and HBJ report subawards from LSHTM to Christian Medical College. QB and AB reports subawards from LSHTM to ISGlobal and Centro de Investigação em Saúde de Manhiça. AA and CN reports subawards from the LSHTM to the University of Oxford. CRN. reports subawards from LSHTM to Kenya Medical Research Institute, Kilifi, Kenya. CSY reports subawards from LSHTM to Fundación INFANT. RL reports subawards from LSHTM to Fundación INFANT. a grant from Program for Appropriate Technology in Health for a respiratory syncytial virus (RSV) costing study, grants to Fernando Polack from the Bill & Melinda Gates Foundation for estimating the RSV burden of disease, consulting fees and participating for serving on Pfizer’s GBS advisory board and Janssen’s RSV advisory board, payment or honoraria for Janssen’s RSV lecture and Merck’s human papillomavirus lecture, and stock or stock options from iTRIALS. FS reports non-financial support from The Federal University of São Paulo for submitted work and employment by the UK NSC hosted by the Department of Health, who developed the maternal GBS screening policy recommendation in the UK.  All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© 2022 The Author(s).)