Clinical and virological profile of locally acquired acute hepatitis E in South Bulgaria.

INTRODUCTION: Acute hepatitis E virus (HEV) infection is recognized as a zoonosis in several European countries. We describe the characteristics and outcomes of locally acquired acute HEV hepatitis. METHODOLOGY: A prospective study was conducted among adult patients with acute HEV hepatitis at the University Hospital in Plovdiv, South Bulgaria between January 2020 and May 2022. An acute HEV infection case was a patient with acute hepatitis and laboratory-confirmed anti-HEV IgM antibodies and/or HEV RNA in serum. Demographic data, clinical manifestations, laboratory test results, and outcomes were recorded. RESULTS: A total of 46 patients were selected. Median age of 65 years (interquartile range [IQR] 50.8-74.3). 28 (60.87%) were male. 22 (47.83%) had comorbidities such as diabetes (15), liver cirrhosis (3), hepatitis B virus infection (2), and malignancies (2). Of the 46, 18 (39.13%) patients were viremic and, HEV genotype 3 was detected. The median (IQR) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet, and international normalized ratio levels were 992 (495.8-1714.3) U/L, 715 (262.5-1259.3) U/L, 204 (132.3-235.5) µmol/L, 204 (132.3-235.5) ×109 L, and 1.0 (0.89-1.19), respectively. Six patients with underlying liver diseases had severe hepatitis. A young patient with osteoarthritis progressed to acute liver failure and died. The persistent HEV infection was ruled out in 2 malignant patients who tested HEV RNA negative three months after discharge. CONCLUSIONS: Acute HEV hepatitis is a diagnosis to consider after excluding other causes of acute viral hepatitis. A diagnostic workup should include timely testing for HEV to identify the most vulnerable to severe consequences.

Ventilator-Associated Pneumonia in the Neonatal Intensive Care Unit-Incidence and Strategies for Prevention.

The second most prevalent healthcare-associated infection in neonatal intensive care units (NICUs) is ventilator-associated pneumonia (VAP). This review aims to update the knowledge regarding the incidence of neonatal VAP and to summarize possible strategies for prevention. The VAP incidence ranges from 1.4 to 7 episodes per 1000 ventilator days in developed countries and from 16.1 to 89 episodes per 1000 ventilator days in developing countries. This nosocomial infection is linked to higher rates of illness, death, and longer hospital stays, which imposes a substantial financial burden on both the healthcare system and families. Due to the complex nature of the pathophysiology of VAP, various approaches for its prevention in the neonatal intensive care unit have been suggested. There are two main categories of preventative measures: those that attempt to reduce infections in general (such as decontamination and hand hygiene) and those that target VAP in particular (such as VAP care bundles, head of bed elevation, and early extubation). Some of the interventions, including practicing good hand hygiene and feeding regimens, are easy to implement and have a significant impact. One of the measures that seems very promising and encompasses a lot of the preventive measures for VAP are the bundles. Some preventive measures still need to be studied.

Hepatitis E Virus (HEV) Infection among Hemodialysis Patients from Southern Bulgaria.

Viral hepatitis B and C are widely recognized problems in hemodialysis (HD) patients. There have been increasing reports of the importance of the hepatitis E virus (HEV) in recent years, but the worldwide data on the seroprevalence of HEV among them are conflicting. The aim of the present study was to assess the seroprevalence of HEV in HD patients and to analyze the predictors of seropositivity. This study was conducted in 2020 in the central part of southern Bulgaria. A total of 225 patients were enrolled. An enzyme-linked immunosorbent assay for the determination of anti-HEV IgM/IgG was used. All patients were tested for the presence of HEV RNA. Anti-HEV IgM alone and anti-HEV IgG alone were found in 6 (2.7%) and 14 (6.2%) patients, respectively, and in 4 (1.8%) patients, they were found simultaneously. All patients were HEV RNA-negative. The overall HEV seroprevalence was 10.7% (24/225). The binominal logistic regression analysis of available predictors confirmed the role of vascular access and a duration of dialysis treatment over 5 years as predictors significantly associated with increased risk for HEV, and the consumption of bottled water with lower levels of HEV IgG seroprevalence among hemodialysis patients. The accumulated data are the basis for comparative analysis in subsequent trials in the same dialysis centers and for enhancing the range of screening markers used in this particular patient group.

Age and Gender Trends in the Prevalence of Markers for Hepatitis E Virus Exposure in the Heterogeneous Bulgarian Population.

The prevalence of hepatitis E virus (HEV) in the Bulgarian population remains underestimated. The aim of the present study was to evaluate age and gender trends in HEV prevalence in the heterogeneous Bulgarian population. Stored serum samples from blood donors and different patient sub-populations-kidney recipients (KR), patients with Guillain-Barre syndrome (GBS), Lyme disease (LD), patients with liver involvement and a clinical diagnosis other than viral hepatitis A and E (non-AE), hemodialysis (HD) and HIV-positive patients (HIV)-were retrospectively investigated for markers of past and recent/ongoing HEV infection. The estimated overall seroprevalence of past infection was 10.6%, ranging from 5.9% to 24.5% for the sub-populations evaluated, while the seroprevalence of recent/ongoing HEV infection was 7.5%, ranging from 2.1% to 20.4%. The analysis of the individual sub-populations showed a different prevalence with respect to sex. In regard to age, the cohort effect was preserved, as a multimodal pattern was observed only for the GBS sub-population. Molecular analysis revealed HEV 3f and 3e. The type of the population is one of the main factors on which the anti-HEV prevalence depends, highlighting the need for the development of guidelines related to the detection and diagnosis of HEV infection with regard to specific patient populations.

When two viruses collide: coronavirus disease after hepatitis B virus reactivation.

The COVID-19 pandemic has exploded since the first cases were reported in Wuhan in December 2019, engulfing the globe. Many infected individuals are asymptomatic or have a mild or moderate disease. A subset of people with advanced age, the immunocompromised and those with chronic diseases, are prone to serious-to-critical illness. We report a fatal case of metastatic colorectal cancer survivor who developed COVID-19 after clinically reactivated hepatitis B virus (HBV) due to chemotherapy. The patient's COVID-19 illness was supposed to be related to her recent medical evaluation. Although being diagnosed with chronic HBV infection for decades, she was not treated with nucleotide analogue and the possibility to preclude HBV reactivation was missed. Moreover, infectious control practices must be draconian in order to save such a fragile population from infections.

Stochastic modelling of scalar time series of varicella incidence for a period of 92 years (1928-2019).

INTRODUCTION: Varicella is an acute, highly contagious disease, characterised by generalised vesicular exanthema caused by the initial infection with varicella zoster virus (VZV) which usually affects children aged 2 to 8 years. AIM: To analyse the changes of varicella incidence in Bulgaria over the period of 1928-2019. MATERIALS AND METHODS: The time series analysis is based on the official data for varicella incidence (per 100,000) in Bulgaria for ninety-two years (1928-2019), obtained from three major sources. We utilized the method to construct a time series model of overall incidence (1928-2019) using time series modeller in SPSS v. 25. We followed all three steps of the standard ARIMA methodology to establish the model - identification, parameter estimation, and diagnostic checking. RESULTS: Stochastic scalar time series modelling of the varicella incidence from 1928 to 2019 was performed. The stochastic ARIMA (0,1,1) was identified to be the most appropriate model. The decomposition of varicella incidence time series into a stochastic trend and a stationary component was reasoned based on the model defined. In addition, we assessed the importance of the long-term and immediate effect of one shock. The long-term forecast was also under discussion. CONCLUSIONS: The ARIMA model (0,1,1) in our study is an adequate tool for presenting the varicella incidence trend and is suitable to forecast near future disease dynamics with acceptable error tolerance.

Ventilator-Associated Pneumonia in Neonates Admitted to a Tertiary Care NICU in Bulgaria.

Ventilator-associated pneumonia (VAP) is the second most common hospital-acquired infection (HAI) among neonatal patients in the intensive care units (ICUs) and is a serious challenge for neonatologists because it affects critically ill patients who need prolonged mechanical ventilation. In Bulgaria, there is no detailed data at regional and national levels on the characteristics of VAP in newborns, which imposes a necessity for specific studies of risk factors and etiology of VAP. The aim of the study was to analyze the frequency, characteristics and risk factors for the occurrence of VAP in newborns hospitalized in intensive care unit. This was a prospective study, conducted between January 2017 and June 2018 in the NICU of University Hospital "St. George" Plovdiv, Bulgaria. The sample consisted of 507 neonates, followed up prospectively, 107 of whom were placed on mechanical ventilation for ≥48 h. VAP was diagnosed in 33 out of 107 neonates (31%). The VAP incidence rate was 35.06/1.000 ventilator days. We confirmed differences between the median birth weight (1,310 vs. 1,690 g, p = 0.045) and average gestational age (31.08 g.w. vs. 33.08 g.w, p = 0.04) of the patients with and without VAP. The average stay of patients with VAP in the NICU was statistically significantly longer than the hospital stay of non-VAP patients (35.70 ± 21.84 days vs. 21.77 ± 17.27 days (t = 3.241, p = 0.002). In neonates with VAP, the duration of mechanical ventilation was statistically significantly longer compared with non-VAP patients (16.88 ± 11.99 vs. 5.42 ± 4.48; t = 5.249, p = 0.000). A statistically significant prevalence of Gram-negative bacteria among VAP patients was demonstrated (91%) compared to the Gram-positive (9%), p < 0.05. The leading causative agent of VAP was Klebsiella pneumoniae ESBLs + (27%), followed by Acinetobacter baumannii (14%), Pseudomonas aeruginosa (12%) and Escherichia coli (12%). In multivariate logistic regression, mechanical ventilation >7 days was established as an independent risk factor for VAP (OR 3.6; 95% CI: 1.7-6.5, p = 0.003). VAP remains a serious and outstanding issue in pediatric and neonatal intensive care units. The findings of the current study emphasize that the birth weight, gestational age, and duration of hospital stay have a significant association with ventilator-associated pneumonia.

Cost Analysis for Patients with Ventilator-Associated Pneumonia in the Neonatal Intensive Care Unit.

The concept of improving the quality and safety of healthcare is well known. However, a follow-up question is often asked about whether these improvements are cost-effective. The prevalence of nosocomial infections (NIs) in the neonatal intensive care unit (NICU) is approximately 30% in developing countries. Ventilator-associated pneumonia (VAP) is the second most common NI in the NICU. Reducing the incidence of NIs can offer patients better and safer treatment and at the same time can provide cost savings for hospitals and payers. The aim of the study is to assess the direct costs of VAP in the NICU. This is a prospective study, conducted between January 2017 and June 2018 in the NICU of University Hospital "St. George" Plovdiv, Bulgaria. During this period, 107 neonates were ventilated for more than 48 h and included in the study. The costs for the hospital stay are based on the records from the Accounting Database of the setting. The differences directly attributable to VAP are presented both as an absolute value and percentage, based on the difference between the values of the analyzed variables. There are no statistically significant differences between patients with and without VAP in terms of age, sex, APGAR score, time of admission after birth and survival. We confirmed differences between the median birth weight (U = 924, p = 0.045) and average gestational age (t = 2.14, p = 0.035) of the patients in the two study groups. The median length of stay (patient-days) for patients with VAP is 32 days, compared to 18 days for non-VAP patients (U = 1752, p < 0.001). The attributive hospital stay due to VAP is 14 days. The median hospital costs for patients with VAP are estimated at €3675.77, compared to the lower expenses of €2327.78 for non-VAP patients (U = 1791.5, p < 0.001). The median cost for antibiotic therapy for patients with VAP is €432.79, compared to €351.61 for patients without VAP (U = 1556, p = 0.024). Our analysis confirms the results of other studies that the increased length of hospital stays due to VAP results in an increase in hospital costs. VAP is particularly associated with prematurity, low birth weight and prolonged mechanical ventilation.

Reporting adverse events of COVID-19 vaccines: The case of Bulgaria.

As a member state of the European Union, where vaccines against COVID-19 are available and affordable, Bulgaria reports the lowest immunization coverage and the most pronounced vaccine distrust. The present study aimed to assess the self-reported adverse reactions following COVID-19 vaccination as a possible tool to increase the trust in vaccines. A cross-sectional survey-based study, covering 761 vaccinated respondents, was conducted in Plovdiv (469 with an mRNA vaccine and 292 with an adenoviral vector vaccine). Descriptive statistics parametric and non-parametric methods were applied. Statistical significance was set at p<0.05. The median age of the respondents was 42 years, females (72.5%). At least one adverse reaction was reported in 89.9% of those immunized with mRNA vaccine and 93.8% in the adenoviral vector vaccine group (p>0.05). They were mild to moderate and resolved within several days. The levels of local reactions were comparable: 91.7% in those who received mRNA and 89.7% in those who received an adenoviral vector vaccine (p = 0.366). The most common types of systemic reactions were fatigue, headache, and muscle pains. An association was found between the systemic reactions and the type of vaccine administered: 59.7% in mRNA recipients and 89.4% in adenoviral vector vaccinees (p<0.001). None of the registered systemic reactions required medical attention. There were 3 reports of generalized urticaria after an mRNA and 2 after an adenoviral vector vaccine. The reported reactions are relatively high but expected and no adverse events have been reported that are not listed in the official Summary of Product Characteristics.

Assessment of hepatitis E seropositivity among HIV-infected patients in Bulgaria.

It is debatable whether HIV-infected patients are at greater risk for hepatitis E virus (HEV) infection compared with healthy subjects. The reported anti-HEV seroprevalence among different groups in Bulgaria varied from 9.04% to 25.9%, but the information regarding the HIV population is still missing. The aim of the present study was to evaluate hepatitis E seroprevalence among HIV-infected patients in Bulgaria and to analyze demographic and immunological factors associated with HEV infection. Serum samples of 312 HIV-infected patients were analyzed retrospectively. Age, sex, residence and laboratory markers for HEV, HBV, HCV and HIV infection, and lymphocytes subpopulations were collected for all patients. None of the tested samples were positive for HEV RNA. HEV seroprevalence among HIV-infected patients was 10.9%. Males were more affected with the highest prevalence of positivity in the age group > 30 to ≤ 40 years. The documented HIV transmission routes in HIV/HEV co-infected group were heterosexual, homosexual, intravenous drug use (IDU), and vertical with predominace of the heterosexual route (z = 0.2; p = 0.804). There was a statistically significant trend of HIV mixed infection with routes of HIV transmission other than homosexual - heterosexual in HIV/HEV group and injection drug use in HIV/HBV/HCV co-infected group. The route of HIV transmission, in contexts of patients' behavior, was associated with HEV prevalence among HIV-infected patients.

Assessment of hepatitis E seropositivity among HIV-infected patients in Bulgaria

Abstract It is debatable whether HIV-infected patients are at greater risk for hepatitis E virus (HEV) infection compared with healthy subjects. The reported anti-HEV seroprevalence among different groups in Bulgaria varied from 9.04% to 25.9%, but the information regarding the HIV population is still missing. The aim of the present study was to evaluate hepatitis E seroprevalence among HIV-infected patients in Bulgaria and to analyze demographic and immunological factors associated with HEV infection. Serum samples of 312 HIV-infected patients were analyzed retrospectively. Age, sex, residence and laboratory markers for HEV, HBV, HCV and HIV infection, and lymphocytes subpopulations were collected for all patients. None of the tested samples were positive for HEV RNA. HEV seroprevalence among HIV-infected patients was 10.9%. Males were more affected with the highest prevalence of positivity in the age group > 30 to ≤ 40 years. The documented HIV transmission routes in HIV/HEV co-infected group were heterosexual, homosexual, intravenous drug use (IDU), and vertical with predominace of the heterosexual route (z = 0.2; p = 0.804). There was a statistically significant trend of HIV mixed infection with routes of HIV transmission other than homosexual - heterosexual in HIV/HEV group and injection drug use in HIV/HBV/HCV co-infected group. The route of HIV transmission, in contexts of patients' behavior, was associated with HEV prevalence among HIV-infected patients.

Epidemiological Prognosis of Pertussis Incidence in Bulgaria.

INTRODUCTION: Epidemiological forecasting facilitates scientifically sound solutions to upcoming theoretical and practical issues, in the development of public health management, in particular of infectious diseases. AIM: To critically analyze the most recent scientific advances in the biosocial nature and methodology of epidemiological forecasting to present a real-life example of pertussis, a disease with shifting epidemiology. MATERIALS AND METHODS: For the prediction of pertussis morbidity the autoregressive integrated moving average (ARIMA) the model was established by utilizing the method of time series analysis to construct a model of overall morbidity using Time series modeller in SPSS v.25. To model pertussis morbidity we obtained official data from the Ministry of Health and the National Center for Infectious and Parasitic Diseases, since the beginning of disease registration from 1903 until 2018. We also analyzed the shifting epidemiology of pertussis. RESULTS: The proper identification procedures we applied indicated ARIMA (3,0,0) model to best fit our original time series of the annual whooping cough morbidity for the 1921-2018 period. The model predicts better morbidity in a one-step forecast. The incidence rate is expected to be stable at about 1.35 per 100,000 in the next three years, which is close to the 2016 level and lower than those in 2017-2018. CONCLUSION: The ARIMA (3,0,0) model in our study is an adequate tool for presenting the pertussis morbidity trend and is suitable to forecast near-future disease dynamics, with acceptable error tolerance.

Mediterranean spotted fever in child and adult patients: investigation from an endemic region in Bulgaria.

OBJECTIVES: Mediterranean spotted fever (MSF) is a tick-borne endemic disease caused by Rickettsia conorii conorii and transmitted to humans by the brown dog tick Rhipicephalus sanguineus. It is characterized by fever, maculopapular rash and a tick bite skin lesion "tache noire". The disease affects all age groups and usually has mild to moderate course. It has long been considered a benign infection. However, very severe "malignant" forms with fatal outcome strongly influenced by the patients' age were also observed. We aimed to reveal the features of MSF in children by comparing them with some of the disease patterns in adults. METHODS: Our prospective study data are based on the monitoring of all inpatients of the Clinic of Infectious Diseases in Plovdiv City and environs, the largest MSF endemic region in Bulgaria. The total number of patients admitted and treated for MSF over a study period of 10 years is 549, the incidence reaching 9.44/100,000. MSF is confirmed by antibody response to a specific antigen measured by indirect immunofluorescence assay (IFA). IgG ≥ 128 and/or IgM > 64 were considered to be indicative of acute infection. RESULTS: Eighty-five (15.48%) patients were children up to 14 years of age and 464 (84.52%) were aged 15-85 years. The skin lesion "tache noire" was present in 73.68% of children, and in 76.93% of the older age groups; symptoms as anorexia, nausea, vomiting, abdominal pain, and diarrhoea were more frequent in children, till general weakness and malaise was prevalent in adults. Children accounted approximately for 70% of the disease mild forms. No lethality was registered in this age group. Even though there were isolated cases of severe and malignant forms, children did not undergo the fatal complications seen in adults. CONCLUSION: Knowledge of the peculiarities of MSF in children will contribute to children's health protection, timely diagnose and disease prevention.

Surveillance of Nosocomial Infections in a Bulgarian Neonatal Intensive Care Unit.

INTRODUCTION: Nosocomial infections (NI) are frequent complications in neonatal intensive care units (NICU) which result in high morbidity and mortality. AIM: To determine and analyze the incidence, risk factors and etiologic agents of NI in newborns admitted in the NICU to help plan-ning future surveillance and prevention strategies. MATERIALS AND METHODS: A prospective cohort study was carried out at the NICU of St George University Hospital, Plovdiv, Bul-garia from January 1, 2017 to June 31, 2018. The number of neonates included in the study was 507. Descriptive statistics such as count,  percent, mean and standard deviation was used. Chi-square test was performed to prove associations. Odds ratios, with 95% confidence intervals, were computed from the results of the binominal logistic regression analyses. RESULTS: Of the 507 hospitalized newborns in NICU, 48 presented with 54 NI. The incidence and the density incidence rates were 9.5% and 7.67 per 1,000 patient-days, respectively. Nosocomial infections were detected in neonates from all birth weight (BW) classes, but it was low BW and premature neonates that were at major risk to acquire them. The most common infection sites were ventilator-asso-ciated pneumonia (VAP) (67.27%), bloodstream infection (23.64%) and conjunctivitis (9.09%). Major pathogens were Gram-negative such as Klebsiella pneumoniae, E. coli, Pseudomonas aeruginosa and Acinetobacter baumannii. In the multivariate logistic regression analysis NIs were strongly associated with intubation, presence of a venous catheter, the duration of antibiotic treatment and increased CRP> 10 mg/l. CONCLUSIONS: This report highlights the burden of NIs, identifies the major focus for future NI control and prevention programs.

Bisphosphonate-associated Osteonecrosis of the Jaws: a Survey of the Level of Knowledge of Dentists about the Risks of Bisphosphonate Therapy.

INTRODUCTION: Bisphosphonate-associated osteonecrosis of the jaws (BAONJ) is a side effect of treatment with bisphosphonate (BP). Reports of this complication have increased recently. AIM: To evaluate the level of knowledge of dentists from Plovdiv, Bulgaria, about possible complications of bisphosphonate therapy of patients in dental practice. MATERIALS AND METHODS: Three hundred and twenty-three dental practitioners from Plovdiv, Bulgaria, took part in an anonymous survey containing 25 questions, designed to evaluate the knowledge of dentists about the complications of BP therapy. RESULTS: Oral and maxillofacial surgeons have the best knowledge about the indications and side effects of BP therapy, while dentists with a specialty in Pediatric Dentistry and General Dentistry have insufficient knowledge. Of the respondents, 17.03% are absolutely uninformed about BP and their side effects, and 1/2 declare that they have never had a patient with complications from BP therapy in their practice, probably due to a lack of awareness of the problem. Approximately half of the dentists we surveyed agree to carry out prophylactic examinations of patients receiving BP and know what the prophylactic examination includes. Only 15.48% of the respondents have correctly responded that in order to be treated as clinically healthy, patients should have stopped taking BP for more than 10 years. CONCLUSION: With the exception of specialists in Oral and Maxillofacial Surgery, dental practitioners in Plovdiv and the region are poorly informed about the complications associated with BP therapy. Therefore, efforts must be made to make these dentists better informed about BAONJ, especially about the methods and means of preventing this condition.

Booster immunity - diagnosis of chronic hepatitis B viral infection.

INTRODUCTION: Diagnosis of chronic hepatitis B virus (HBV) infection particularly its occult form requires monitoring and repeat serological and molecular studies. The aim of the study was to investigate the possible relation between the case of a family outbreak of hepatitis A and the finding that a member of this family was diagnosed with chronic hepatitis B. METHODOLOGY: A mother and her two sons, one previously diagnosed with chronic HBV infection, were hospitalized due to suspected acute hepatitis. Serological markers for hepatitis A, hepatitis B and hepatitis C were assessed. Additionally, HBV DNA was tested with a sensitive PCR. Hepatitis B vaccine was administered to the mother to differentiate resolved from occult HBV infection. RESULTS: A family outbreak of hepatitis A was confirmed, alongside a focus of chronic HBV infection. The serological profile for two brothers was HBsAg(+), anti-HBcIgM(-), anti-HBc(+), HBcAg(-)/anti-HBe(+). The mother was negative for all HBV markers except anti-HBc. HBV DNA was detected at a level of 461 IU/mL in the elder brother, 3647 IU/mL in the younger brother and was negative in the mother on two occasions. Her anti-HBc alone, having two sons with chronic HBV infection, and her lack of antibody response to hepatitis B vaccine despite being negative for HBV DNA, led to the diagnosis of probable occult HBV infection. CONCLUSION: Our results confirmed that a vaccination approach could facilitate diagnosis of chronic HBV infection in the presence of isolated anti-HBc. If it were not for a family outbreak of hepatitis A, this unexpected family HBV focus would not have been revealed.

A Technical Problem in Diagnosis Clarity of Solitary Spinal Cord Neurofibroma in an Eleven-month-old Boy.

Spinal neurofibroma is one of the rarest of the neoplasms involving the spinal cord or roots and occurs much less often than neurinoma, meningioma or glioma. The sixth pediatric case of solitary intramedullary tumor was described in 2013, according to B. Eljebbouri et al. We present a rare, difficult to diagnose and may-be the seventh pediatric case of solitary neurofibroma of the cauda equine in an 11-month-old infant. The patient underwent a laminectomy of T12, L1, L2 and L3, extirpation of intradural, intramedullary and extramedullary spinal cord tumor. The patient is fully recovered for 5 years of monitoring. Although rare, spinal neurofibromas in children should be diagnostically considered and radically treated for a favorable outcome.

Prevalence of HBV and HCV among outpatients in the Plovdiv region of Bulgaria, 2010-2011.

Viral hepatitis, particularly hepatitis B and C, are diseases with worldwide distribution that present a significant public health problem. Seroprevalence studies allow assessment of the extent of the disease burden, the identification of populations at risk and the monitoring trends over time. A multi-center seroprevalence study, carried out in Bulgaria (covering the five largest cities - Sofia, Plovdiv, Varna, Pleven, and Stara Zagora) in 1999-2000 estimated a crude seroprevalence rate of 3.9% for HBsAg and 1.3% for anti-HCV. A decade later, comparable rates were observed in a study including 865 outpatients consulting a clinical laboratory in Plovdiv, the second largest administrative region in Bulgaria. The crude seroprevalence rate measured for hepatitis B (HBsAg) was 3.9%. The HBsAg prevalence rate in individuals ≤19 years of age (targeted by vaccination) was significantly lower compared to the rate in adults ≥20 years of age -1% versus 4.8%. The lack of dynamics in the overall level of HBsAg carriers is likely related to the excessively low hepatitis B vaccine coverage in individuals, born before the introduction of the universal vaccination of newborns in August 1991. Anti-HCV antibodies were detected in 0.7% of the subjects.

Immune memory and immune response in children from Bulgaria 5-15 years after primary hepatitis B vaccination.

BACKGROUND: Bulgaria adopted the World Health Organization recommendation of routine universal infant vaccination against hepatitis B in 1991. Nevertheless, only a few studies evaluated the protection after the vaccination against hepatitis B, especially in children. The objective of this study was to investigate the duration of protection against hepatitis B in children aged 5-15 years after primary immunization, by measuring the immune and anamnestic immune response and possible breakthrough infections. METHODS: A total of 141 children (aged 5-17 years) were recruited randomly and divided into 3 groups, approximately 5 years (group 1), 10 years (group 2) and 15 years (group 3) after primary immunization with a recombinant hepatitis B vaccine; they were tested for hepatitis B markers: hepatitis B surface antigen anti-hepatitis core antibody and antibodies to hepatitis B surface antigen (anti-HB). A booster dose of vaccine was administered to 23 children with titers of anti-HBs antibodies below the threshold considered to be protective (<10 mIU/mL). Anti-HBs concentrations and geometric mean concentration (GMC) were determined before and 21-28 days after the booster vaccination. RESULTS: Protective anti-HBs antibodies were detected in 95 of 141 (67.4 %) tested children, with a GMC of 63.57 mIU/mL. The seroprotection rate and GMC by groups was respectively: 84.6% and GMC of 76.05 mIU/mL in group 1; 55.8% and GMC of 58.1 mIU/mL in group 2; and 61.1% and GMC of 50.33 mIU/mL in group 3. Hepatitis B surface antigen and anti-hepatitis core antibody were found in 1 of the 141 subjects (0.7%). Of the remaining 140 children, 95 had anti-HBs ≥10 mIU/mL, and anti-hepatitis core antibodies were not detected. A booster dose of hepatitis B vaccine was administered to 23 of 45 (51%) children with anti-HBs <10 mIU/mL. Anamnestic immune response was shown in 100% of the children: the GMC was 337.38 mIU/mL and protective antibodies ranged between 15 and 955 mIU/mL. CONCLUSION: The study demonstrates the presence of immune memory and protection 5-15 years after the initial course of newborn immunization with recombinant vaccines against hepatitis B.