Chronic Carriers Research Articles

Biocenosis of the vagina and modern approaches to the correction of vaginal dysbiosis (Literature review)

In the modern world it is important to understand the interaction of macro- and microorganisms in normal conditions and during illness. It is the biotope of the vagina that plays an extremely important role in a woman’s organism and it reflects the general state of woman’s health. Urogenital endogenous microflora is not static, it is a constantly changing macropopulation. In this population the number of specific types of microorganisms fluctuates within the limits of changes in the conditions of their environment. The microflora of the vagina changes during different periods of a woman’s life, namely during perinatal, late neonatal, prepubertal, pubertal, reproductive and postmenopausal periods, as well as the menstrual cycle, daily and hourly. The ability of commensal microorganisms to protect the region from the invasion of their own microflora from other cavities and the microflora of the sexual partner is unique. Considering the general global trend towards the increase in prevalence, virulence and resistance of microorganisms to traditional methods of antiseptic therapy, as well as the appearance of new types of microorganisms, a steady trend towards an increase in infectious diseases, including sexually transmitted infections, is determined. Dysbiosis is considered qualitative and quantitative violations of the corresponding biotope of the normal flora. According to official statistics, the prevalence of bacterial vaginosis is 10-35% among all patients with pathological vaginal discharge. The variability of the vaginal microbiome is widely studied in the world and depends on many factors, namely the hormonal background of a woman’s organism, her diet, the characteristics of urination and defecation, menstruation, hygienic procedures and infections. One of the key links in the pathogenesis of vaginal infectious diseases is the ability of bacteria to form biofilms, which are microbial associations. Infections caused by film-forming strains of pathogenic and opportunistic microorganisms are characterized by an atypical course, insufficient effectiveness of antibiotic therapy, and often transition to a chronic form or carriage. Therefore, understanding the mechanisms of formation, structure and regulation of vital activities of biofilms helps in solving problems related to human health. The World Health Organization recommends evaluating the vaginal microbiome according to the Hay – Ison criteria. Determining the pH of vaginal secretions also helps to establish the type of vaginal dysbiosis. Clinical therapy includes two main stages of treatment: antiseptic measures and restoration of one’s own vaginal microbiome. Often, these two stages of therapy are carried out simultaneously. Correcting the pH of the vaginal secretion is also important.

Triple motif proteins 19 and 38 correlated with treatment responses and HBsAg clearance in HBeAg-negative chronic hepatitis B patients during peg-IFN-α therapy

ObjectiveTo investigate whether the expression of triple motif protein 19/38 (TRIM19/38) mRNA in peripheral blood mononuclear cells (PBMCs) of HBeAg-negative chronic hepatitis B virus (HBV) carriers is associated with the response to pegylated interferon alpha (peg-IFN-α) treatment and HBsAg clearance.MethodsIn this prospective study, HBeAg-negative chronic HBV carriers treated with peg-IFN-α completed 48 weeks of follow-up. After treatment with peg-IFN-α, the patients were divided into responders (R group) and nonresponders (NR group) according to the changes in HBV DNA and HBsAg levels at week 48 of treatment. According to whether serum HBsAg loss or seroconversion occurred, the patients were divided into a serological response group (SR group) and a nonserological response group (NSR group). The level of TRIM19/38 mRNA in PBMCs was detected by real-time fluorescence quantitative PCR. The diagnostic performance of TRIM19/38 was analysed by calculating the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).Results43 HBeAg-negative chronic HBV carriers, 35 untreated CHB patients and 19 healthy controls were enrolled in this study. We found that TRIM19/38 mRNA levels were significantly lower in untreated CHB patients than in healthy controls. In HBeAg-negative chronic HBV carriers who underwent prospective follow-up, TRIM19/38 mRNA levels were negatively correlated with HBV DNA and ALT at baseline. Among the patients treated with peg-IFN-α, 16 patients achieved a treatment response (R group) and 27 patients did not achieve a treatment response (NR group). Compared with baseline, HBsAg levels in the R group decreased significantly at 12 and 24 weeks of treatment; at the early stage of peg-IFN-α treatment, the dynamic changes in TRIM19/38 mRNA levels in the R and NR groups were different, and the TRIM19/38 mRNA levels in the R group were significantly higher than those in the NR group, especially at 24 weeks of treatment. ROC curve analysis showed that the changes in mRNA levels of TRIM19 and TRIM38 predicted the treatment response, with AUCs of 0.694 and 0.757, respectively. Among the patients treated with peg-IFN-α, 11 patients achieved a serological response (SR group) and 32 patients did not achieve a serological response (NSR group). Compared with baseline, HBsAg levels in the SR group decreased significantly at 12 and 24 weeks of treatment; TRIM19/38 mRNA levels were significantly higher in the SR group than in the NSR group at week 24.ConclusionThe higher level of TRIM19/38 mRNA in PBMCs of HBeAg-negative chronic HBV carriers may be related to the early treatment effect of peg-IFN-α and HBsAg clearance. TRIM19 and TRIM38 have clinical significance in predicting virological response and guiding treatment regimens.

Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Confirmation Of African Swine Fever Virus in Some Pigs from Ado Local Government Area of Benue State, Nigeria

Studies were undertaken to investigate and isolate African Swine Fever virus in pig in Ado local government area (LGA) of Benue state of Nigeria and this has confirmed the carrier status of the pigs in the LGA. Out of the 188 serum samples collected, 7 were obtained from the LGA and were tested using Enzyme Linked Immunosorbent Assay (ELISA). Three samples (42.86%) were positive and 4(57.14%) were negative for the test. All the serum samples (42.86%) that were positive by ELISA were also positive by polymerase chain reaction amplification (PCR). The PCR-positive pigs had higher mean WBC count, lower eosinophil and basophils count, higher mean monocytes count but the mean PCV values were not significantly different from the normal and PCR negative pigs. High mean WBC count may indicate an ongoing secondary bacterial and ASF virus infection, lower eosinophil and basophils count indicates parasitism in the pigs, higher mean monocytes count. This confirmed that pigs with demonstrable antibody should be considered as chronic carriers of the virus because it is doubtful if true recovery ever occurs. Control measures such as use of biosecurity, test and slaughter of animals that test positive for African Swine Fever (ASF) antibody with adequate compensation are suggested to eradicate the disease.

HBsAg protein composition and clinical outcomes in chronic hepatitis D and variations across HBeAg-negative chronic HBsAg carriers

HBsAg proteins are useful to identify HBV inactive carriers (ICs), but data on chronic hepatitis D (CHD) are scarce. This study aimed to describe HBsAg composition in CHD, its changes during the evolution, and the potential association with clinical outcomes. In addition, we assess the composition of HBsAg across different HBV genotypes and validate previous results on HBsAg proteins in an independent HBV cohort. Quantitative HBsAg, medium HBsAg proteins (MHBs), and large HBsAg proteins (LHBs) were measured in two cohorts. The first cohort consisted of patients with CHD. A cross-sectional study of samples from two European institutions (N =46) was conducted. Outcomes were assessed in a retrospective-prospective study of those patients with a follow-up of >1 year (n=36), and the longitudinal evolution of HBsAg proteins in those with samples >5 years apart (n=12) was analysed. The second cohort consisted of patients with HBeAg-negative HBV, and a cross-sectional study was performed (N=141). Forty-one (89%) patients with CHD had detectable HDV-RNA, and the presence of HDV-RNA was associated with higher LHBs proportion (p=0.010). Baseline MHBs (p=0.051) and MHBs proportion (p=0.086) tended to be higher in those developing clinical outcomes (9/36, 25%) after a median follow-up of 5.9 years. Patients in which HDV-RNA became spontaneously undetectable during follow-up (5/31, 16.1%) tended to present lower MHBs proportion (p= 0.085). In the longitudinal study, changes in LHBs proportion were observed (p=0.041), whereas MHBs proportion remained stable (p=0.209). Regarding HBV, ICs showed lower LHBs proportion (p=0.027). LHBs and MHBs differed significantly according to HBV genotype, regardless of the HBV phase. Patients with CHD with detectable HDV-RNA presented higher LHBs proportion than those with undetectable HDV-RNA. A trend toward having higher baseline MHBs proportion was observed in patients who developed clinical outcomes or remained with detectable HDV-RNA. This study validates the different HBsAg composition in HBV ICs and reveals the HBV-genotype influence in HBsAg composition. The composition of HBsAg in chronic hepatitis D differs in patients with detectable and undetectable HDV viral load and may help predict the likelihood of achieving undetectable HDV viraemia and the development of clinical events such as decompensation. The composition of the surface antigen is also useful to distinguish inactive carriers of HBV, and it varies according to HBV genotype.

Enteric Fever: Diagnostic Challenges and the Importance of Early Intervention.

Enteric fever is a systemic infection caused by highly virulent Salmonella entericaserovars: Typhi and Paratyphi. Diagnosis of enteric fever is challenging due to a wide variety of clinical features which overlap with other febrile illnesses. The current diagnostic methods are limited because of the suboptimal sensitivity of conventional tests like blood culture in detecting organisms and the invasive nature of bone marrow culture. It emphasizes the need to develop improved and more reliable diagnostic modalities. The rising rates of multidrug-resistant Salmonella strains call for an accurate understanding of the current management of the disease. Proper public health measures and large-scale immunization programs will help reduce the burden of the disease. A comprehensive surveillance system can help detect the chronic carrier state and is crucial in understanding antibiotic susceptibility patterns. We conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar till May 2022. The following search words and medical subject headings (MeSH) were used: "enteric fever," "Salmonella Typhi," "multidrug-resistant Salmonella," chronic carrier state," "Salmonella detection, "and "typhoid vaccine." We reviewed the literature on clinical features, pathophysiology, new diagnostic tests, and interventions to prevent the disease. This article explores enteric fever and its various clinical features and addresses the emerging threat of multidrug resistance. It focuses on novel methods for diagnosis and prevention strategies, including vaccines and the use of surveillance systems employed across different parts of the world.

Hepatitis B virus associated cirrhosis: overview of prognostic and management

Hepatitis B virus (HBV) infection is a global public health problem ; two billion people worldwide have evidence of past or present infection with HBV, and 296 million individuals are chronic carriers (i.e., positive for hepatitis B surface antigen [HBsAg]), of whom approximately 887,000 dies annually from HBV-related liver disease: chronic hepatitis B-associated cirrhosis and hepatocellular carcinoma. There are described some risk factors to the development of cirrhosis to HBV-infected persons: alcohol consumption, HBeAg status, metabolic syndrome, HBV genotypes and variants, and the level of HBV replication. The observation of a strong association between the development and decompensation of cirrhosis as well as between the development of HCC and the level of HBV replication suggests that suppression of HBV replication by long-term antiviral treatment may decrease the risk of complications in patients with HBV-related cirrhosis. The indication for antiviral treatment is given if any HBV DNA levels are detectable in the serum of HBV-infected patients with cirrhosis. Into the new era of antiviral treatment with nucleos(t)ide analogs we can prevent the development of cirrhosis in patients with chronic HBV infection and hepatic decompensation in many patients with HBV-related cirrhosis.

Stenotrophomonas maltophilia natural history and evolution in the airways of adults with cystic fibrosis.

Stenotrophomonas maltophilia is an opportunistic pathogen infecting persons with cystic fibrosis (pwCF) and portends a worse prognosis. Studies of S. maltophilia infection dynamics have been limited by cohort size and follow-up. We investigated the natural history, transmission potential, and evolution of S. maltophilia in a large Canadian cohort of 321 pwCF over a 37-year period. One-hundred sixty-two isolates from 74 pwCF (23%) were typed by pulsed-field gel electrophoresis, and shared pulsotypes underwent whole-genome sequencing. S. maltophilia was recovered at least once in 82 pwCF (25.5%). Sixty-four pwCF were infected by unique pulsotypes, but shared pulsotypes were observed between 10 pwCF. In chronic carriage, longer time periods between positive sputum cultures increased the likelihood that subsequent isolates were unrelated. Isolates from individual pwCF were largely clonal, with differences in gene content being the primary source of genetic diversity objectified by gene content differences. Disproportionate progression of CF lung disease was not observed amongst those infected with multiple strains over time (versus a single) or amongst those with shared clones (versus strains only infecting one patient). We did not observe evidence of patient-to-patient transmission despite relatedness between isolates. Twenty-four genes with ≥ 2 mutations accumulated over time were identified across 42 sequenced isolates from all 11 pwCF with ≥ 2 sequenced isolates, suggesting a potential role for these genes in adaptation of S. maltophilia to the CF lung. Genomic analyses suggested common, indirect sources as the origins of S. maltophilia infections in the clinic population. The information derived from a genomics-based understanding of the natural history of S. maltophilia infection within CF provides unique insight into its potential for in-host evolution.

In Shortly About Hepatitis B

Hepatitis B is an infectious liver disease caused by the hepatitis B virus, which can be mild and last for several weeks, but also a serious lifelong infection (chronic hepatitis B). Acute hepatitis B lasts up to 6 months and is usually of a milder form, but it can also be more severe and require hospitalization. If the organism fails to overcome the viruses, the disease turns into a chronic form that can cause major consequences. Hepatitis B is one of the most common infectious diseases, and it is estimated that there are around 300 million chronic HBV carriers worldwide. The most common route of transmission is after a puncture or cut on an infected needle or other sharp object and the sexual route

Assessment of knowledge and treatment practices of hepatitis B infection in children among health professionals in Krachi districts in Ghana: a cross-sectional study.

Hepatitis B virus (HBV) infection remains one of the neglected infectious diseases. Children infected with HBV are at higher risk of becoming chronic carriers. Barriers to measures against HBV in children are attributed to inadequate knowledge by some health professionals. This study assessed knowledge and treatment practices of HBV in children among health professionals. A cross-sectional survey was conducted among health professionals (185) in three districts in Krachi using a structured questionnaire. Stata version 15 was used to analyze participants' responses on awareness, knowledge, and treatment practices. Pearson's product-moment correlation was used to determine the relationship between knowledge and treatment practices. Multivariate regression analysis assessed the relationships between variables at P<0.05 and 95% confidence interval. 20% were not aware of HBV in children and 85% had only fair knowledge about HBV in children. Only 29% indicated good knowledge and treatment practices of HBV in children. A unit increase in knowledge of HBV in children leads to a 1.42 unit increase in awareness (P<0.01), and a 1.3 unit increase in treatment practice (P<0.01) of HBV in children. Participants demonstrated only fair knowledge about HBV in children. Seminars and workshops on HBV in children for health professionals must intensify.

Common Genetic Variants of Response to Hepatitis B Vaccines Correlate with Risks of Chronic Infection of Hepatitis B Virus: A Community-Based Case-Control Study.

Hepatitis B (HB) vaccination effectively reduces the risks of chronic infection with the hepatitis B virus (HBV). It is unknown whether there is a common genetic determinant for response to the HB vaccine and susceptibility to chronic HBV infection. This case-control study, which included 193 chronic HBV carriers and 495 non-carriers, aimed to explore the effects of the most significant single nucleotide polymorphisms (SNPs) in response to the HB vaccine on the risks of chronic HBV infection. Out of 13 tested SNPs, the genotype distributions of four SNPs at the human leukocyte antigen (HLA) class II region, including rs34039593, rs614348, rs7770370, and rs9277535, were significantly different between HBV carriers and non-carriers. The age-sex-adjusted odds ratios (OR) of chronic HBV infection for rs34039593 TG, rs614348 TC, rs7770370 AA, and rs9277535 AA genotypes were 0.51 (95% confidence interval [CI], 0.33-0.79; p = 0.0028), 0.49 (95% CI, 0.32-0.75; p = 6.5 × 10-4), 0.33 (95% CI, 0.18-0.63; p = 7.4 × 10-4), and 0.31 (95% CI, 0.14-0.70; p = 0.0043), respectively. Multivariable analyses showed that rs614348 TC and rs7770370 AA genotypes were significantly independent protectors against chronic HBV infection. The multivariable-adjusted ORs for subjects with none, either one, or both of the protective genotypes were 1.00 (referent), 0.47 (95% CI: 0.32-0.71; p = 3.0 × 10-4), and 0.16 (95% CI: 0.05-0.54; p = 0.0032), respectively. Among eight HBeAg-positive carriers, only one of them carried a protective genotype. This study shows that response to the HB vaccine and susceptibility to chronic HBV infection share common genetic determinants and indicates that HLA class II members are the main responsible host genetic factors.

What Should We Be Recommending for the Treatment of Enteric Fever?

Patients with suspected enteric (typhoid and paratyphoid) fever are predominantly managed as outpatients in endemic regions. Nonspecific clinical presentation, lack of accurate diagnostic tools, and widespread antimicrobial resistance makes management challenging. Resistance has been described for all antimicrobials including chloramphenicol, amoxycillin, trimethoprim-sulfamethoxazole, ciprofloxacin, ceftriaxone, and azithromycin. No significant differences have been demonstrated between these antimicrobials in their ability to treat enteric fever in systematic reviews of randomized controlled trials (RCTs). Antimicrobial choice should be guided by local resistance patterns and national guidance. Extensively drug-resistant typhoid isolates require treatment with azithromycin and/or meropenem. Combining antimicrobials that target intracellular and extracellular typhoid bacteria is a strategy being explored in the Azithromycin and Cefixime in Typhoid Fever (ACT-SA) RCT, in progress in South Asia. Alternative antimicrobials, such as the oral carbapenem, tebipenem, need clinical evaluation. There is a paucity of evidence to guide the antimicrobial management of chronic fecal carriers.

Modelling of Hepatitis B Virus vertical transmission dynamics in Ethiopia: a compartmental modelling approach

BackgroundHepatitis B (HB) is a virus which causes a potentially fatal liver infection. It is a DNA virus belonging to the Hepadnaviridae virus family. Africa, after Asia, has the second highest number of chronic HBV carriers and is considered a high-endemic region. Ethiopia is classified as a country with a high prevalence of viral hepatitis and with nations that lack a systematic strategy for viral hepatitis surveillance.MethodsS-I-C-R deterministic model was developed and the numerical simulations were done in “R” statistical and programming software. Fixed population assumption was considered so as to develop a simple model which could predict the HBV vertical transmission for the next 5 decades.ResultsThe model revealed that significant number of populations will be infected and become carrier till the end the next 49 years even though it has decreasing trend. It was predicted that 271,719 people will die of HBV complications if no intervention will be made on its vertical transmission. The sensitivity analysis result showed that the force of infection has the most important parameter in the vertical transmission dynamics of hepatitis B. Provision of hepatitis B immunoglobulin (HBVIG) and vaccines at the time of delivery could decrease the force of infection by more than half and 51,892 lives will be saved if the intervention is offered for 50% of deliveries in Ethiopia.ConclusionDespite the fact that the incidence of HBV vertical transmission is substantial, it is expected to decline during the next five decades. However, the situation necessitates immediate attention, since it results in thousands of deaths if no action is taken. Offering HBVIG and vaccinations to the 50% of infants can save many lives and reduces the force of infection by more than a half.

Early Detection of Epstein-Barr Virus as a Risk Factor for Chronic High Epstein-Barr Viral Load Carriage at a Living-donor-dominant Pediatric Liver Transplantation Center.

Epstein-Barr virus (EBV) infection and posttransplant lymphoproliferative disorders (PTLDs) after pediatric liver transplantation (LT) account for significant morbidity and mortality. Knowledge of EBV kinetics, epidemiology, and outcomes among pediatric living-donor LT cases is largely lacking. This study aims to provide clinical information related to EBV infection, chronic high EBV load (CHL) carriage, and PTLD at a living-donor-dominant pediatric LT center. A total of 5827 EBV load measurements from 394 LT recipients fulfilling inclusion criteria and their clinical data were analyzed. EBV loads >1000 copies/μg DNA (742 IU/μg DNA) were considered "high," and CHL was defined by persistence >6 mo. The highlighted results were as follows: (1) 94% of recipients underwent living-donor LT; (2) 80% of EBV seronegative recipients developed first EBV infection <2 y post-LT, and their EBV loads were consistently higher than those of seropositive recipients within <3 y post-LT but did not differ thereafter; (3) 61 (15%) recipients met CHL criteria, but none developed PTLD; (4) age <5 y, cytomegalovirus seronegative donors, and early development of EBV DNAemia <6 mo post-LT were independent risk factors for CHL; (5) the incidence of rejections after 1-y post-LT was comparably low among CHL carriers whose immunosuppression was minimized. Early detection of EBV following LT and CMV seronegative donors would facilitate risk stratification to prevent PTLD while titrating immunosuppression among pediatric LT recipients.

P12 COMPLEX LEAD EXTRACTION: A PERCUTANEOUS MULTIDISCIPLINARY APPROACH

Abstract Introduction The infection represents one of the most serious complications of implantable cardiac systems (ICDs and PMs) and is associated with increased mortality and significant expenditure of financial resources. The incidence, which ranges from 0.6 to 3.4%, depends by the patient characteristics, the type of implanted system, and from other factors related to the procedure itself. When diagnosed, it is recommended extraction of the system. A 77–year–old patient, hypertensive, obese, former tobacco user, suffering from chronic ischemic heart disease and carrier of bicameral PM since 2019 for BAV grade III. In June 2022 decubitus of the PM pocket. Considering the negativity of coltural tests and the absence of fever, it was decided to use a conservative approach by doing a curettage of the pocket and by repositioning the device at the submuscular level. After about a month, a reappearance of decubitus with exposure of the PM case occurred, therefore, a complete extraction of the leads and removal of the device was performed. The surgery, performed under general anaesthesia, was complicated by the fracture of both leads at the level of the anonymous vein. With the introduction of dedicated ligature through the right femoral vein, it was possible to successfully extract the ventricular lead stump. During the recapture of the atrial stump, a migration of the stump into the right ventricle and then into the pulmonary circulation to a terminal branch of the right pulmonary artery occurred. The recovery of such stump was possible with the help of interventional radiologists and through the use of a dedicated material (“Gooseneck ligature catheter”). Subsequent implantation of temporary PM by the right jugular given the absence of underlying spontaneous rhythm. Conclusions CIED extraction surgery is burdened with a high risk of complications even serious ones, including lead rupture and distal fragment embolization. A multidisciplinary approach with shared choices and techniques allowed the resolution percutaneous resolution of a complex picture.

A CROSS-SECTIONAL STUDY TO FIND OUT THE PROPORTION OF HEPATITIS B VIRUS INFECTION AND ITS ASSOCIATED RISK FACTORS AMONG PREGNANT WOMEN ATTENDING ANTENATAL CLINIC IN TERTIARY HEALTH CARE CENTER IN CENTRAL INDIA

Background: Hepatitis B virus (HBV) infection continues to be a life- threatening health problem throughout world, infecting more than two billion people. While blood transfusion and unsafe therapeutic injection continue to be major risk factors, the role of vertical transmission remains under- estimated. Hence, this study was done to nd out the prevalence of HBV infection and associated risk factors among healthy pregnant women in Central India Indore (M.P.). The present study was a prospective, cross-sectional study conducted, in the department of Microbiology of M.G.M. Medical College from June 2021 to June 2022. Methodology: After receiving 5 ml of blood sample in the Microbiology Laboratory, serum was separated by centrifugation. They were then tested for Hepatitis B surface antigen (HBsAg) by Rapid Test and Enzyme linked Immunosorbent assay (ELISA). Results: Total 610 samples were screened among which 12 (%) were tested positive for HBsAg. Pregnant women found with history of blood transfusion was found to be 5(41.66%), followed by tattooing which was 33.33%, followed by history of multiple sexual partners, HIV positive and family history of HBV infection which was 8.33%,8.33% and 8.33% respectively. Conclusion: Perinatal transmission is the major route of HBV transmission in the absence of prophylaxis, a large proportion of viremic mothers transmits infection to neonates. Immunization is the most effective and only way of preventing development of chronic carrier state. Hence all neonates were administered with hepatitis B vaccine and 0.5 ml of hepatitis B immunoglobulin within 12 hours of birth

Hepatitis B virus-induced hepatocellular carcinoma: a persistent global problem.

Hepatitis B virus (HBV) infections are highly prevalent globally, representing a serious public health problem. The diverse modes of transmission and the burden of the chronic carrier population pose challenges to the effective management of HBV. Vaccination is the most effective preventive measure available in the current scenario. Still, HBV is one of the significant health issues in various parts of the globe due to non-response to vaccines, the high number of concealed carriers, and the lack of access and awareness. Universal vaccination programs must be scaled up in neonates, especially in the developing parts of the world, to prevent new HBV infections. Novel treatments like combinational therapy, gene silencing, and new antivirals must be available for effective management. The prolonged infection of HBV, direct and indirect, can promote the growth of hepatocellular carcinoma (HCC). The present review emphasizes the problems and probable solutions for better managing HBV infections, causal risk factors of HCC, and mechanisms of HCC.

The Characteristics of the Biological Markers of Pregnant Women Carrying the Hepatitis B Virus in the Hepato-Gastroenterology Unit of the District Hospital of Commune IV in Bamako (Mali)

Introduction: Hepatitis B virus (HBV) infects more than 2 billion people worldwide, with more than 257 million chronic carriers and 88,700 deaths per year. In Mali, the prevalence of HBsAg in the general population is estimated at 14.7% [2] and 15.5% in pregnant women. The objective of this work was to describe the characteristics of the biological markers of pregnant women carrying the hepatitis B virus in the hepato-gastroenterology unit of the district hospital of commune IV of Bamako (Mali). Patients and Methods: This was a descriptive cross-sectional study that took place at the district hospital of commune IV of Bamako between March 1, 2020 and February 1, 2021. The study population was consisting of pregnant women referred to our unit for positive HBSAg detected during prenatal biological examinations. Were included in this study, the pregnant women referred for Ag HBS positive and who made the biological markers of follow-up. Were not included, those who did not make the biological markers. Results: During the study period, we received 177 pregnant carriers of the hepatitis B virus out of 1008 consultations, ie a frequency of 13.09%. Among the 177 pregnant women referred to our unit, 132 were able to carry out the biological markers, i.e. a completion rate of 74.58%. The age of the patients varied between 16 and 44 years with an average age of 28.5 years ± 6.6. HBsAg was discovered in 81.1% of women during the current pregnancy and it was prior to pregnancy in 18.9%. Positive viral markers in pregnant women were: HBeAg (6.8%), anti- HBe Ac (84.8%), anti - HBc Ac IgG (100%). Viral DNA was undetectable in 17.4% of pregnant women, it was between 1-2 million IU/ml in 77.3% and greater than 2 million IU/ml in 5.3%. Conclusion: This study showed a high frequency of hepatitis B virus infection during pregnancy. A better knowledge of serological markers, particularly in pregnant women, seems to be the most effective means of combating this scourge.

Abstract 3013: The immunogenetic basis of hepatitis B virus-related hepatocellular carcinoma

Abstract Background: The reported associations of genetic variants within the human leukocyte antigen (HLA) region with hepatis B virus (HBV)-related hepatocellular carcinoma (HCC) are not consistent, and the structure-function patterns involved in this disease remain unclear. Methods: Utilizing genotype data from 706 HBV-related HCC cases and 6197 chronic HBV carriers without HCC collected from three resources in Taiwan, we imputed the classical HLA alleles at 2-field resolution and analyzed the molecular landscape of HLA complexes by deeply dissecting their genotypic configurations, functional divergence, and HBV-antigen binding capabilities in associations with the HCC risk. Logistic regression models were used, and all models were adjusted for sex, age, and population structure using the top 10 principal components. We also tested the underlying biological implications of our findings by investigating the HLA binding affinities and HLA effect on control of viral replication (i.e, HBV DNA load), viral population diversity (i.e, quasispecies), and inflammation (i.e, chemokines, cytokines, and soluble programmed cell death 1 [sPD-1]-associated T cell exhaustion). Results: We found high accuracy (≥95% concordance) of HLA imputation at all HLA class I and class II alleles. The strongest evidence for an association with HCC was observed for HLA-DQB1*03:01 (adjusted OR= 1.35 in an additive genetic model, P=1.3×10-6). Three amino acids at specific positions within or near the peptide-binding groove of DQB1 molecules might explain the observed allele association, which leads to loss of binding HBV nucleocapsid protein (i.e., low binding affinity predicted by NetMHCIIpan 4.0 for HLA-DQB1*03:01). HLA-DQB1*03:01 was significantly associated with a higher HBV DNA load (P= 4.3×10-4) and an increased level of serum sPD-1 (P=6.8×10-4), but not with increased levels of chemokines, cytokines, and viral complexity (i.e., Shannon entropy for HBV quasispecies, all P values&amp;gt;0.05). Analysis of HLA zygosity confirmed that HLA-DQB1 heterozygosity was associated with a decreased risk of HCC (adjusted OR=0.77, P= 0.015). Analysis of HLA evolutionary divergence (HED) showed that high HED at HLA-DRB1 loci was marginally associated with a decreased risk of HCC among HLA-DQB1*03:01 non-carriers (P=0.05). Conclusion: Our data shed light on the immunogenetic risk associated with HBV-related HCC. The effect of HLA-DQB1*03:01 could be partly explained by its low binding affinity with HBV nucleocapsid antigen, and/or its effect on viral load control and sPD-1, but not by its control on other inflammation markers (chemokines and cytokines) and viral population diversity. The association between HLA-DQB1 heterozygosity and HCC risk could be independent of the HLA-DQB1*03:01 effect, which indicates underlying mechanisms related to increased immunosurveillance in clearing potential viral antigens or neoantigens. Citation Format: Zhiwei Liu, Chih-Jen Huang, Yu-Han Huang, Mei-Hung Pan, Mei-Hsuan Lee, Mathias Viard, Allan Hildesheim, Ruth M. Pfeiffer, Mary Carrington, Chien-Jen Chen, Tobias L. Lenz, Hwai-I Yang. The immunogenetic basis of hepatitis B virus-related hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3013.

Chronic Salmonella Typhi carriage at sites other than the gallbladder.

Typhoid fever caused by infection with Salmonella enterica subspecies enterica serotype Typhi (S. Typhi), an important public health problem in many low- and middle-income countries, is transmitted by ingestion of water or food contaminated by feces or urine from individuals with acute or chronic S. Typhi infection. Most chronic S. Typhi carriers (shedding for ≥12 months) harbor infection in their gallbladder wherein preexisting pathologies, particularly cholelithiasis, provide an environment that fosters persistence. Much less appreciated is the existence of non-gallbladder hepatobiliary chronic S. Typhi carriers and urinary carriers. The former includes parasitic liver flukes as a chronic carriage risk factor. Chronic urinary carriers typically have pathology of their urinary tract, with or without renal or bladder stones. Even as the prevalence of multidrug-resistant and extensively drug-resistant S. Typhi strains is rising, global implementation of highly effective typhoid vaccines is increasing. There is also renewed interest in identifying, monitoring, and (where possible) treating chronic carriers who comprise the long-term reservoir of S. Typhi.