Early antenatal care: does it make a difference to outcomes of pregnancy associated with syphilis? A systematic review and meta-analysis.

Despite an increase in the proportion of women who access antenatal care, mother-to-child transmission of syphilis continues to be a consequence of undiagnosed, untreated, or inadequately treated maternal syphilis. We reviewed evidence on the optimal timing of antenatal interventions to prevent mother-to-child transmission of syphilis and its associated adverse outcomes

Global burden of maternal and congenital syphilis in 2008 and 2012: a health systems modelling study

Background: In 2007, WHO launched a global initiative for the elimination of mother-to-child transmission of syphilis (congenital syphilis). An important aspect of the initiative is strengthening surveillance to monitor progress towards elimination. In 2008, using a health systems model with country data inputs, WHO estimated that 1·4 million maternal syphilis infections caused 520 000 adverse pregnancy outcomes. To assess progress, we updated the 2008 estimates and estimated the 2012 global prevalence and cases of maternal and congenital syphilis. Methods: We used a health systems model approved by the Child Health Epidemiology Reference Group. WHO and UN databases provided inputs on livebirths, antenatal care coverage, and syphilis testing, seropositivity, and treatment in antenatal care. For 2012 estimates, we used data collected between 2009 and 2012. We updated the 2008 estimates using data collected between 2000 and 2008, compared these with 2012 estimates using data collected between 2009 and 2012, and performed subanalyses to validate results. Findings: In 2012, an estimated 930 000 maternal syphilis infections caused 350 000 adverse pregnancy outcomes including 143 000 early fetal deaths and stillbirths, 62 000 neonatal deaths, 44 000 preterm or low weight births, and 102 000 infected infants worldwide. Nearly 80% of adverse outcomes (274 000) occurred in women who received antenatal care at least once. Comparing the updated 2008 estimates with the 2012 estimates, maternal syphilis decreased by 38% (from 1 488 394 cases in 2008 to 927 936 cases in 2012) and congenital syphilis decreased by 39% (from 576 784 to 350 915). India represented 65% of the decrease. Analysis excluding India still showed an 18% decrease in maternal and congenital cases of syphilis worldwide. Interpretation: Maternal and congenital syphilis decreased worldwide from 2008 to 2012, which suggests progress towards the elimination of mother-to-child transmission of syphilis. Nonetheless, maternal syphilis caused substantial adverse pregnancy outcomes, even in women receiving antenatal care. Improved access to quality antenatal care, including syphilis testing and treatment, and robust data are all important for achieving the elimination of mother-to child transmission of syphilis. Funding: The UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction in WHO, and the US Centers for Disease Control and Prevention

Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data

Background The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥90% of pregnant women to be tested for syphilis and ≥90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Methods and Findings Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was “probable active,” and for testing and treatment coverage. Conclusions Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed

Estimating the effect of HIV on cervical cancer elimination in South Africa: comparative modelling of the impact of vaccination and screening

Background In 2020, the World Health Organization (WHO) launched its initiative to eliminate cervical cancer as a public health problem. To inform global efforts for countries with high HIV and cervical cancer burden, we assessed the impact of human papillomavirus (HPV) vaccination and cervical cancer screening and treatment in South Africa, on cervical cancer and the potential for achieving elimination before 2120, considering faster HPV disease progression and higher cervical cancer risk among women living with HIV(WLHIV) and HIV interventions. Methods Three independent transmission-dynamic models simulating HIV and HPV infections and disease progression were used to predict the impact on cervical cancer incidence of three scenarios for all women: 1) girls' vaccination (9–14 years old), 2) girls' vaccination plus 1 lifetime cervical screen (at 35 years), and 3) girls’ vaccination plus 2 lifetime cervical screens (at 35 and 45 years) and three enhanced scenarios for WLHIV: 4) vaccination of young WLHIV aged 15–24 years, 5) three-yearly cervical screening of WLHIV aged 15–49 years, or 6) both. Vaccination assumed 90% coverage and 100% lifetime protection with the nonavalent vaccine (against HPV-16/18/31/33/45/52/58). Cervical cancer screening assumed HPV testing with uptake increasing from 45% (2023), 70% (2030) to 90% (2045+). We also assumed that UNAIDS 90-90-90 HIV treatment and 70% male circumcision targets are reached by 2030. We examined three elimination thresholds: age-standardised cervical cancer incidence rates below 4 or 10 per 100,000 women-years, and >85% reduction in cervical cancer incidence rate. We conducted sensitivity analyses and presented the median age-standardised predictions of outcomes of the three models (minimum–maximum across models). Findings Girls' vaccination could reduce age-standardised cervical cancer incidence from a median of 47.6 (40.9–79.2) in 2020 to 4.5 (3.2–6.3) per 100,000 women-years by 2120, averting on average ∼4% and ∼46% of age-standardised cumulative cervical cancer cases over 25 and 100 years, respectively, compared to the basecase. Adding 2 lifetime screens helped achieve elimination over the century among all women (2120 cervical cancer incidence: 3.6 (1.9–3.6) per 100,000 women-years), but not among WLHIV (10.8 (5.3–11.6)), and averted more cumulative cancer cases overall (∼45% over 25 years and ∼61% over 100 years compared to basecase) than girls' vaccination alone. Adding three-yearly cervical screening among WLHIV (to girls' vaccination and 2 lifetime cervical screens) further reduced age-standardised cervical cancer incidence to 3.3 (1.8–3.6) per 100,000 women-years overall and to 5.2 (3.9–8.5) among WLHIV by 2120 and averted on average 12–13% additional cumulative cancer cases among all women and 21–24% among WLHIV than girls’ vaccination and 2 lifetime cervical screens over 25 years or longer. Long-term vaccine protection and using the nonavalent vaccine was required for elimination. Interpretation High HPV vaccination coverage of girls and 2 lifetime cervical screens could eliminate cervical cancer among women overall in South Africa by the end of the century and substantially decrease cases among all women and WLHIV over the short and medium term. Cervical cancer elimination in WLHIV would likely require enhanced prevention strategies for WLHIV. Screening of WLHIV remains an important strategy to reduce incidence and alleviate disparities in cervical cancer burden between women with and without HIV, despite HIV interventions scale-up. Funding World Health Organization. National Cancer Institute, National Institutes of Health. MRC Centre for Global Infectious Disease Analysis, UK Medical Research Council. National Institute of Child Health and Human Development research. Cancer Association of South Africa. Canadian Institutes of Health Research and the Fonds de recherche du Québec – Santé research

Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics

Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 μg l−1; PGC, 13.2 μg l−1; PGA/PGC, 6.7; and gastrin, 62.4 ng l−1. For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test

SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis

OBJECTIVES: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Major databases between 1 December 2019 and 3 August 2021. STUDY SELECTION: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal). RESULTS: 472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean. CONCLUSION: SARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication

Lipopolysaccharide Diversity Evolving in Helicobacter pylori Communities through Genetic Modifications in Fucosyltransferases

Helicobacter pylori persistently colonizes the gastric mucosa of half the human population. It is one of the most genetically diverse bacterial organisms and subvariants are continuously emerging within an H. pylori population. In this study we characterized a number of single-colony isolates from H. pylori communities in various environmental settings, namely persistent human gastric infection, in vitro bacterial subcultures on agar medium, and experimental in vivo infection in mice. The lipopolysaccharide (LPS) O-antigen chain revealed considerable phenotypic diversity between individual cells in the studied bacterial communities, as demonstrated by size variable O-antigen chains and different levels of Lewis glycosylation. Absence of high-molecular-weight O-antigen chains was notable in a number of experimentally passaged isolates in vitro and in vivo. This phenotype was not evident in bacteria obtained from a human gastric biopsy, where all cells expressed high-molecular-weight O-antigen chains, which thus may be the preferred phenotype for H. pylori colonizing human gastric mucosa. Genotypic variability was monitored in the two genes encoding α1,3-fucosyltransferases, futA and futB, that are involved in Lewis antigen expression. Genetic modifications that could be attributable to recombination events within and between the two genes were commonly detected and created a diversity, which together with phase variation, contributed to divergent LPS expression. Our data suggest that the surrounding environment imposes a selective pressure on H. pylori to express certain LPS phenotypes. Thus, the milieu in a host will select for bacterial variants with particular characteristics that facilitate adaptation and survival in the gastric mucosa of that individual, and will shape the bacterial community structure

The overmethylated genes in Helicobacter pylori-infected gastric mucosa are demethylated in gastric cancers

<p>Abstract</p> <p>Background</p> <p>The transitional-CpG sites between weakly methylated genes and densely methylated retroelements are overmethylated in the gastric mucosa infected with <it>Helicobacter pylori </it>(<it>H. pylori</it>) and they are undermethylated in the gastric cancers depending on the level of loss of heterozygosity (LOH) events. This study delineated the transitional-CpG methylation patterns of CpG-island-containing and -lacking genes in view of the retroelements.</p> <p>Methods</p> <p>The transitional-CpG sites of eight CpG-island-containing genes and six CpG-island-lacking genes were semi-quantitatively examined by performing radioisotope-labelling methylation-specific PCR under stringent conditions. The level of LOH in the gastric cancers was estimated using the 40 microsatellite markers on eight cancer-associated chromosomes. Each gene was scored as overmethylated or undermethylated based on an intermediate level of transitional-CpG methylation common in the <it>H. pylori</it>-negative gastric mucosa.</p> <p>Results</p> <p>The eight CpG-island genes examined were overmethylated depending on the proximity to the nearest retroelement in the <it>H. pylori</it>-positive gastric mucosa. The six CpG-island-lacking genes were similarly methylated in the <it>H. pylori</it>-positive and -negative gastric mucosa. In the gastric cancers, long transitional-CpG segments of the CpG-island genes distant from the retroelements remained overmethylated, whereas the overmethylation of short transitional-CpG segments close to the retroelements was not significant. Both the CpG-island-containing and -lacking genes tended to be decreasingly methylated in a LOH-level-dependent manner.</p> <p>Conclusions</p> <p>The overmethylated genes under the influence of retroelement methylation in the <it>H. pylori</it>-infected stomach are demethylated in the gastric cancers influenced by LOH.</p