Elevated rates of horizontal gene transfer in the industrialized human microbiome.

Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization.

Core competencies in applied infectious disease epidemiology: a framework for countries in Europe.

In 2009, the European Centre for Disease Prevention and Control (ECDC) developed a competency framework to support European Union countries and the European Commission in ensuring a competent public health workforce for Europe. The coronavirus disease (COVID-19) pandemic emphasised the importance of harmonised public health strategies and competencies across international boundaries, specifically for infectious diseases. This perspective presents the process to update the competency framework for applied infectious disease epidemiology, highlighting ECDC's efforts to support countries with using the framework. ECDC commissioned the Association of Schools of Public Health in the European Region (ASPHER) to update the framework through publication and dissemination of a technical report and a self-assessment tool linked to training resources. A mixed methods approach to gather input from experts in relevant specialities included qualitative interviews with 42 experts, workshops with ECDC Technical Advisory Group and an online survey of 212 public health professionals across Europe and beyond. Modifications resulted in 157 core competencies in 23 domains, each mapping to one of six subject areas of importance in applied infectious disease epidemiology. The framework serves as a basis to update the curriculum of the ECDC Fellowship programme with two alternative paths: intervention epidemiology or public health microbiology.

"True" Helicobacter pylori infection and non-cardia gastric cancer: A pooled analysis within the Stomach Cancer Pooling (StoP) Project.

BACKGROUND: Helicobacter pylori is the most important risk factor for non-cardia gastric cancer (NCGC); however, the magnitude of the association varies across epidemiological studies. This study aimed to quantify the association between H. pylori infection and NCGC, using different criteria to define infection status. METHODS: A pooled analysis of individual-level H. pylori serology data from eight international studies (1325 NCGC and 3121 controls) from the Stomach Cancer Pooling (StoP) Consortium was performed. Cases and controls with a negative H. pylori infection status were reclassified as positive considering the presence of anti-Cag A antibodies, gastric atrophy, or advanced stage at diagnosis, as available and applicable. A two-stage approach was used to pool study-specific adjusted odds ratios (OR), and 95% confidence intervals (95% CI). A meta-analysis of published prospective studies assessing H. pylori seropositivity in NCGCs was conducted. RESULTS: The OR for the association between serology-defined H. pylori and NCGC was 1.45 (95% CI: 0.87-2.42), which increased to 4.79 (95% CI: 2.39-9.60) following the reclassification of negative H. pylori infection. The results were consistent across strata of sociodemographic characteristics, clinical features and lifestyle factors, though significant differences were observed according to geographic region-a stronger association in Asian studies. The pooled risk estimates from the literature were 3.01 (95% CI: 2.22-4.07) for ELISA or EIA and 9.22 (95% CI: 3.12-27.21) for immunoblot or multiplex serology. CONCLUSION: The NCGC risk estimate from StoP based on the reclassification of H. pylori seronegative individuals is consistent with the risk estimates obtained from the literature. Our classification algorithm may be useful for future studies.

A nationwide cross-sectional review of in-hospital hepatitis B virus testing and disease burden estimation in Ghana, 2016 - 2021.

BACKGROUND AND AIMS: Data are needed to inform hepatitis B virus (HBV) testing and treatment policies in Ghana to make progress towards achieving the 2030 WHO elimination targets. This study investigated testing patterns for HBV and described the age, sex, and region-specific prevalence of HBV infection in Ghana using hospital data. METHODS: A nationwide multi-centre cross-sectional study was performed where hospital-based registers were reviewed. These included review of 139,966 laboratory, 169,048 blood bank, and 83,920 delivery register entries from 22 healthcare institutions in Ghana. Frequencies and proportions, and crude and pooled estimates reported. Chi squared test was used for tests of independence. Logistic regression was used to identify factors associated with a positive test result. RESULTS: The crude HBsAg seroprevalence was 8.48% (95%CI 8.25-8.57%) with pooled estimate of 11.40% (95%CI 10.44-12.35). HBsAg seroprevalence among children under 5 years was 1.87% (95%CI 1.07-3.27) and highest age-specific seroprevalence was in those 40-49 years. The highest region-specific seroprevalences was in the Savannah (22.7%). Predictors of a positive HBsAg RDT test included female sex (OR 0.81 95% CI 0.74-0.88), and age (OR 1.005 95%CI 1.002-1.007). The proportion of parturient women receiving HBsAg testing increased between 2017 (87.2%) and 2020 (94.3%) (p < 0.001). The crude HBsAg seroprevalence in parturient women was 6.14% (95% CI 5.97-6.31). Among blood donors the crude HBsAg seroprevalence was 5.69% (95%CI 5.58-5.80). Data from 2 teaching hospitals indicated that in 2020, although 1500 HBsAg positive tests were recorded only 746 serological profile and 804 HBV DNA tests were performed. HBV e antigen seroprevalence was 6.28% (95%CI 4.73-7.84). CONCLUSION AND RECOMMENDATIONS: Ghana remains a country with high HBV burden. There is an unequal distribution, with higher HBsAg seroprevalence in the north of the country. Furthermore, PCR testing is not widely available outside of large teaching hospitals, which limits diagnostic work-up. Hepatitis reporting systems and registers should be improved to facilitate data capture of indicators and standardised across the country to allow for comparability. Furthermore, where gains have been made in testing among pregnant women, there is a need for linkage to appropriate care.

Education and gastric cancer risk-An individual participant data meta-analysis in the StoP project consortium.

Low socioeconomic position (SEP) is a strong risk factor for incidence and premature mortality from several cancers. Our study aimed at quantifying the association between SEP and gastric cancer (GC) risk through an individual participant data meta-analysis within the "Stomach cancer Pooling (StoP) Project". Educational level and household income were used as proxies for the SEP. We estimated pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) across levels of education and household income by pooling study-specific ORs through random-effects meta-analytic models. The relative index of inequality (RII) was also computed. A total of 9,773 GC cases and 24,373 controls from 25 studies from Europe, Asia and America were included. The pooled OR for the highest compared to the lowest level of education was 0.60 (95% CI, 0.44-0.84), while the pooled RII was 0.45 (95% CI, 0.29-0.69). A strong inverse association was observed both for noncardia (OR 0.39, 95% CI, 0.22-0.70) and cardia GC (OR 0.47, 95% CI, 0.22-0.99). The relation was stronger among H. pylori negative subjects (RII 0.14, 95% CI, 0.04-0.48) as compared to H. pylori positive ones (RII 0.29, 95% CI, 0.10-0.84), in the absence of a significant interaction (p = 0.28). The highest household income category showed a pooled OR of 0.65 (95% CI, 0.48-0.89), while the corresponding RII was 0.40 (95% CI, 0.22-0.72). Our collaborative pooled-analysis showed a strong inverse relationship between SEP indicators and GC risk. Our data call for public health interventions to reduce GC risk among the more vulnerable groups of the population.

Ambulatory end-stage liver disease in Ghana; patient profile and utility of alpha fetoprotein and aspartate aminotransferase: platelet ratio index.

BACKGROUND: End-stage liver disease (ESLD) is a major burden on public health, particularly in sub-Saharan Africa, where hepatitis B virus (HBV) is an important risk factor. We aimed to describe clinical characteristics of ESLD from cirrhosis or hepatocellular carcinoma (HCC) and the performance of aspartate aminotransferase (AST)-platelet ratio index (APRI) and alpha fetoprotein (AFP) in Ghana. METHODS: We performed an observational cross-sectional study in outpatient hepatology clinics at three teaching hospitals in Ghana, West Africa. One hundred and forty-one HCC, 216 cirrhosis and 218 chronic HBV patients were recruited by convenience sampling. Sociodemographic, history and examination, laboratory, and disease staging information were shown using descriptive statistics. Performance of the APRI score in diagnosis of cirrhosis and AFP in the diagnosis of HCC was determined using AUROC analysis. RESULTS: Median age at presentation was 44 years for HCC and 46 years for cirrhosis. HBV was found in 69.5% of HCC and 47.2% of cirrhosis cases, and HCV in 6.4% and 3.7% respectively. APRI cut-off of 2 had sensitivity of 45.4% and specificity of 95% in diagnosis of cirrhosis, and cut-off of 1 had sensitivity of 75.9% and specificity of 89%. AUC of AFP was 0.88 (95% CI 0.81-0.94) in diagnosis of HCC. Low monthly income was associated with lower odds of undertaking AFP. Thirty one percent of cirrhotic persons were Child-Pugh C, and 67.9% of HCC patients had advanced or terminal disease at presentation. CONCLUSIONS: Our findings emphasize the young age of ESLD patients in Ghana and the advanced nature at presentation. It highlights shortcomings in surveillance and the need for policies to address the burden and improve outcomes in Ghana.

Prevalence of gastro-esophageal reflux disease and its risk factors in a community-based population in southern India.

BACKGROUND: The prevalence of gastro-esophageal reflux disease (GERD) varies widely around the world. This study aimed to investigate the prevalence and risk factors of GERD in a general population of southern India. METHODS: An interview-based observational study was carried out in southern India during 2010 and early 2011 using a GERD questionnaire (GerdQ). In total 1072 participants were enrolled using a multi-stage cluster sampling method. Presence of GERD was defined as a score of ≥ 8. Logistic regression models were used to derive odds ratios (ORs) with 95 % confidence intervals (CIs). RESULTS: The prevalence of GERD was 22.2 % (238/1072) in southern India, and was more common among older subjects and men. Overweight and obese subjects had a dose-dependent increased risk of GERD, compared to those with body mass index less than 25 (multivariate-adjusted OR = 1.4, 95 % CI 1.0-2.0; OR = 2.3, 95 % CI 1.3-4.1, respectively). People residing in urban community were more vulnerable to GERD than those in rural community (multivariate-adjusted OR = 1.8, 95 % CI 1.3-2.5). Similarly, those with a lower educational level appeared to have an increased risk of GERD. Further, those with a habit of pan masala chewing were more likely to develop GERD compared with those abstained from the habit (multivariate-adjusted OR = 2.0, 95 % CI 1.2-3.2). CONCLUSIONS: GERD is highly prevalent in southern India. Increasing age and BMI, an urban environment, lower educational level, and pan masala chewing appear to be risk factors of GERD symptoms for the studied population.

Osteopontin and latent-TGF ß binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma.

Chronic Hepatitis B (HB) is the main risk factor for chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in many low-resource countries, where diagnosis is constrained by lack of clinical, histopathological and biomarker resources. We have used proteomics to detect plasma biomarkers that outperform α-Fetoprotein (AFP), the most widely used biomarker for HCC diagnosis in low-resource contexts. Deep-plasma proteome analysis was performed in HCC patients, patients with CLD and in HB-carrier controls from Thailand (South-East Asia) and The Gambia (West-Africa). Mass spectrometry profiling identified latent-transforming growth factor ß binding-protein 2 (LTBP2) and Osteopontin (OPN) as being significantly elevated in HCC versus CLD and controls. These two proteins were further analyzed by ELISA in a total of 684 plasma samples, including 183 HCC, 274 CLD and 227 asymptomatic controls. When combined, LTBP2 and OPN showed an area under the receiver operating curve of 0.85 in distinguishing HCC from CLD in subjects with AFP <20 ng/mL. In a prospective cohort of 115 CLD patients from Korea, increased plasma levels of LTBP2 and/or OPN were detected in plasma collected over 2 years prior to diagnosis in 21 subjects who developed HCC. Thus, the combination of LTBP2 and OPN outperformed AFP for diagnosis and prediction of HCC and may therefore improve biomarker-based detection of HBV-related HCC.

GALAD score for the diagnosis of Hepatocellular Carcinoma in sub-Saharan Africa; a validation study in Ghanaian patients.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide including sub-Saharan Africa. The GALAD score, derived from Gender, Age, Lens culinaris agglutinin-reactive fraction of alpha fetoprotein (AFP-L3%), AFP and Des-carboxy-prothrombin (DCP) has high accuracy in diagnosing HCC in Asia, Europe, and North America, however, it has not been validated in an African cohort. The aim of this study was to assess the performance of the GALAD score in the diagnosis of HCC in sub-Saharan Africa. Clinical data from patients with cirrhosis (n=93) or HCC (n=78) from outpatient hepatology clinics at three teaching hospitals in Ghana were abstracted, and serum samples were analyzed. A logistic regression model predicting HCC status based on GALAD score was constructed to obtain the Receiver Operating Characteristics (ROC) curve for GALAD. The area under the curve (AUC) with 95% confidence interval (CI) was calculated. The median GALAD score was higher among HCC patients vs. cirrhosis controls (8.0 vs. -4.1, p<0.01). The AUC of the GALAD score for HCC detection was 0.86 (95% CI 0.79 - 0.92). At a cut-off value of -0.37, the GALAD score had a sensitivity of 0.81 and a specificity of 0.86. The AUC (95% CI) was 0.87 (0.80 - 0.95) and 0.81 (0.67 - 0.94) in HBV positive and HBV negative patients, respectively. The GALAD score has a high accuracy for HCC detection. It has great potential to improve HCC surveillance in sub-Saharan Africa where imaging resources are limited.

Identification of osteopontin as a novel marker for early hepatocellular carcinoma.

UNLABELLED: The aim of this study was to identify a biomarker that could improve alpha-fetoprotein (AFP) performance in hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis. We performed proteomic profiling of plasma from patients with cirrhosis or HCC and validated selected candidate HCC biomarkers in two geographically distinct cohorts to include HCC of different etiologies. Mass spectrometry profiling of highly fractionated plasma from 18 cirrhosis and 17 HCC patients identified osteopontin (OPN) as significantly up-regulated in HCC cases, compared to cirrhosis controls. OPN levels were subsequently measured in 312 plasma samples collected from 131 HCC patients, 76 cirrhosis patients, 52 chronic hepatitis C (CHC) and B (CHB) patients, and 53 healthy controls in two independent cohorts. OPN plasma levels were significantly elevated in HCC patients, compared to cirrhosis, CHC, CHB, or healthy controls, in both cohorts. OPN alone or in combination with AFP had significantly better area under the receiver operating characteristic curve, compared to AFP, in comparing cirrhosis and HCC in both cohorts. OPN overall performance remained higher than AFP in comparing cirrhosis and the following HCC groups: HCV-related HCC, HBV-associated HCC, and early HCC. OPN also had a good sensitivity in AFP-negative HCC. In a pilot prospective study including 22 patients who developed HCC during follow-up, OPN was already elevated 1 year before diagnosis. CONCLUSION: OPN was more sensitive than AFP for the diagnosis of HCC in all studied HCC groups. In addition, OPN performance remained intact in samples collected 1 year before diagnosis.