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.

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.

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.

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.

Shingles: More than Meets the Eye.

Low-dose once weekly methotrexate (MTX) is the first-line disease-modifying antirheumatic drug (DMARD) to treat rheumatoid arthritis and psoriasis. Although methotrexate is generally considered to have a good safety profile it can occasionally induce severe side effects such as pancytopenia, mucositis, disorders of kidney and liver. Oral mucositis should alert physicians to MTX toxicity. We report a 64-year-old woman with a severe drug reaction including disseminated shingles, oral mucositis and pancytopenia only three days after starting a therapeutic low-dose of MTX. Initially, mucositis and myelosuppression couldn't be accounted for by the underlying disease. In taking the patient's history, MTX intake 10 days ago was missed, the patient reporting only current medications. However, there was more to the skin rash than meets the eye. Only after further inquiry did the patient reveal the intake of 2 doses of MTX and the subsequent withdrawal of medication. Arriving at the correct diagnosis in difficult cases, as in the case presented, requires further evaluation, including repeat history taking and eliciting more details if diagnosis remains elusive.

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.

Pulmonary Kaposi's Sarcoma - Initial Presentation of HIV Infection

Kaposi's sarcoma is the most common malignancy associated with human immunodeficiency virus. It commonly affects the skin but can present with visceral involvement, including the lungs. A 23-year-old homosexual male presented with fever, intractable cough and dyspnea. On examination, multiple skin lesions were revealed. Chest computed tomography visualized multiple nodules, bronchoscopy showed endobronchial lesions. Histopathological study of the skin lesions showed Kaposi's sarcoma and the endobronchial biopsy ­ a proliferative inflammatory process. Diagnosis of Kaposi's sarcoma was made based on clinical, laboratory, computed tomography and bronchoscopy data as well as on the regression of pulmonary nodules by the combination antiretroviral therapy. The diagnosis of pulmonary Kaposi's sarcoma is still a challenge due to concomitant occurrence of opportunistic infections. This case emphasizes the need to strongly consider pulmonary KS as a possible cause for respiratory illness in any HIV-positive patient with cutaneous Kaposi's sarcoma.

The Skin and the Eye - Herpes Zoster Ophthalmicus in a Healthy 18-month-old Toddler.

Herpes zoster, caused by reactivation of varicella-zoster virus, is uncommon in infancy. Even more uncommon is herpes zoster ophthalmicus, defined as herpes zoster of the ophthalmic branch of the fifth cranial nerve. Among healthy children, primary varicella-zoster virus infection during gestation as a result of maternal varicella or the first year of life is the major risk factor for development of herpes zoster in a relatively young age. Here we present an unusual case of herpes zoster ophthalmicus with dissemination in an immunocompetent toddler with favorable outcome. The child's mother contracted chickenpox in late pregnancy and her son was very likely infected with varicella-zoster virus in utero. During a two-year follow-up the child vision was normal and there was no evidence of post herpetic neuralgia.

Diagnostic Dilemmas in Hepatitis C Virus Infection for Hemodialysis Patients.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in dialysis patients. The diagnosis of HCV infection in these patients is predominantly based on laboratory tests because of the specificity of the clinical course of the disease. AIM: The present prospective study aimed at determining very accurately the prevalence rate of HCV infection in patients on dialysis by simultaneously testing them for anti-HCV and for HCV RNA levels. MATERIALS AND METHODS: For the present cross-sectional longitudinal study we recruited and followed up 93 patients from St George University Hospital Hemodialysis Unit between July 2013 and December 2014. All patients were tested for anti-HCV and HCV RNA. The anti-HCV negative patients were tested for anti-HCV and HCV RNA at least twice at intervals of 6 months or more (up to 12 months). Anti-HCV antibodies were identified using a third generation ELISA assay. Commercial kits for real-time polymerase chain reaction (RT-PCR) were used to detect HCV RNA in the plasma and mononuclear cells. Aminotransferase and gammaglutamyl transpeptidase levels were studied to find if liver inflammation was present. RESULTS: The total seroprevalence in 68 patients was 20.6% (14). Of these, 10 patients were viremic (HCV RNA+/anti-HCV+), and 4 patients (5.9%) had discordant results (anti-HCV+/HCV RNA-). Acute hepatitis was detected in one patient. Duration of dialysis in HCV viremic patients was longer than that in aviremic patients (p=0.005). CONCLUSIONS: The present study suggests that HCV infection in dialysis patients can be diagnosed more accurately if these patients are tested using two diagnostic methods - a serological test and a biomolecular assay. Further studies with larger sample size may prove the feasibility of such approach for all dialysis patients in this country.

Diversity of human parechoviruses in Bulgaria, 2011: Detection of rare genotypes 8 and 10.

Human parechovirus (HPeV) infections are commonly asymptomatic but are also found in association with symptoms of the gastrointestinal and respiratory tract, or central nervous system. In order to study their distribution and genetic diversity in Bulgaria, specimens from 229 children aged <5years old hospitalized due to neurological manifestations (n=104) and acute gastroenteritis (n=125) were analyzed. Stool samples were tested using reverse transcription followed by real-time polymerase chain reaction toward the 5'UTR region, and the HPeVs detected were identified by PCR directed to VP1 followed by sequencing. HPeV infection rates of 1.9% and 7.2% were found in children presented with neurological symptoms or with acute diarrhea, respectively. Four different HPeV genotypes, HPeV-3 (n=2), HPeV-5 (n=2), HPeV-8 (n=1) and HPeV-10 (n=1) were identified. All but two HPeVs were detected in acute diarrheal cases, while a single HPeV-3 strain and an HPeV-8 strain were detected in association with facial palsy and encephalitis, respectively. This is the first report of HPeV-8 and HPeV-10 in Europe.

Tularemia in bulgaria 2003-2004.

INTRODUCTION: Tularemia is an uncommon but potentially fatal zoonosis. А second outbreak of tularemia in Bulgaria, about 40 years after the first, occurred in 1997 in two western regions, near the Serbian border. In 2003 tularemia reemerged in the same foci. This retrospective study aimed to evaluate the clinical characteristics and the efficacy of antibiotic therapy in a tularemia resurgence in the Slivnitza region in 2003-2004. METHODOLOGY: A total of 26 cases were evaluated. Using medical records, the following data were collected for all patients: symptoms, physical signs, and microbiology results of agglutination tests, cultures and PCR assays. RESULTS: Twenty-four of 26 suspected tularemia patients were laboratory confirmed by agglutination test and/or culture. Fifteen (57.7%) patients had clinical presentation compatible with oropharyngeal, 8 (30.8%) with glandular, and 3 (11.5%) with oculoglandular tularemia. The most frequent symptoms were swollen neck (84.6%) and sore throat (76.9%). Lymphadenopathy (100%) was the most common finding. Francisella tularensis (F. tularensis) was detected by PCR, providing a definitive diagnosis in 82.3% of the cases. All the patients were treated with antibiotics considered effective against F. tularensis; however, therapeutic failure was observed in 23.1% of the cases, which was related to a delay in the initiation of antibiotics. CONCLUSION: The tularemia outbreak in west Bulgaria near the Serbian border was probably food-borne, associated with a surge in the rodent population. The oropharyngeal form was the most common. Although the disease runs a benign course, late initiation of antimicrobial therapy might delay complete recovery.

Clinical and epidemiological features of Lyme borreliosis in Bulgaria.

INTRODUCTION: Data on disease expression and epidemiological characteristics of Lyme borreliosis in south-eastern Europe are scarce. PATIENTS: To reveal features of Lyme borreliosis in Bulgaria, clinical data and epidemiological characteristics of 1257 patients reported between 1999 and 2002 were analysed. RESULTS: The most affected age group was 5-9 years, followed by 45-49 years, 50-54 years, and 10-14 years. Most of the patients (68%) lived in a rural area or were attacked by ticks during activities in a rural area. Lyme borreliosis cases occurred throughout the year with two peaks--one in June and second smaller one in September. The most common clinical manifestation was erythema migrans (EM), diagnosed in 868 (69.1%) of the patients. Rashes had a median diameter of 11 cm and were predominantly located on lower extremities. Forty-four per cent of the rashes consisted of homogenous erythema and 56% had central clearing. Multiple EM was detected in 4.3% of the EM cases. Neuroborreliosis was the second most common presentation of Lyme borreliosis, diagnosed in 19% of the patients. Lyme arthritis was found in 8% of the patients. Heart and ocular manifestations were recorded in 1.1% and 0.9% of the patients, respectively. Borrelial lymphocytoma and acrodermatitis chronica atrophicans were very rare (0.3%). Twenty-seven patients (2.1%) had multiple organ involvement. CONCLUSIONS: The results of the study show that the epidemiology and clinical manifestations of Lyme borreliosis in Bulgaria are similar to those in the majority European countries but possess some distinguishing characteristics.