Stanislav Plíšek

Fulminant hepatitis and death associated with disseminated varicella in an immunocompromised adult from the Czech Republic caused by a wild-type clade 4 varicella-zoster virus strain

Varicella zoster virus typically causes a benign disease in childhood called varicella (chickenpox) and can reactivate in adults as a dermatomally distributed, painful rash illness known as herpes zoster (HZ). Infection with VZV can however lead to severe complications in immunocompromised patients that can result in hospitalization and, occasionally, death. Here we describe a patient, who acquired primary VZV infection during a 3-week-long treatment regimen with corticosteroids. The disease took a fulminant course, leading to a liver failure and severe coagulopathy. The patient died 9 days following hospital admission, despite intensive antiviral and supportive treatment. Wild-type VZV DNA was detected from multiple samples from esophagus, liver and skin. Genotypic analysis based on single nucleotide polymorphism profiles in open reading frames (ORFs) 21, 22 and 50 identified this strain as a clade 4 isolate, which is typically found in tropical countries. This is the first description of a clade 4 strain from a patient in the Czech Republic.

Clinical experience with DTPw-HBV and DTPw-HBV/Hib combination vaccines

Background: Combined diphtheria-tetanus-whole-cell pertussis (DTPw) vaccines remain the cornerstone of many childhood vaccination programs. Larger DTPw-based combination vaccines facilitate high coverage and protection against other childhood pathogens, such as hepatitis B (HBV) and Haemophilus influenzae type b (Hib). Such vaccines have been available since the mid-1990s (Tritanrix™-HBV and Tritanrix™-HBV/Hib; GlaxoSmithKline [GSK] Biologicals), demonstrating excellent immunogenicity in various schedules. In order to address growing demand for DTPw-based vaccines, GSK Biologicals have developed the Zilbrix™ range using a new DTPw antigen source and containing reduced quantities of polyribosylribitol phosphate [PRP]. Objective: This article presents clinical trial results for both DTPw-based vaccines. Methods: GSK Biologicals provided a comprehensive data package, which was supplemented with a Medline literature search. Conclusion: New antigen sources and reduced PRP will ensure the continued supply of DTPw-based combination vaccines for vital global mass vaccination campaigns.

A repeated syphilis infection imported from Thailand in an HIV positive couple of men-who-have-sex-with-men in Czech Republic

Coinfection by HIV and syphilis has become a growing problem due to the re-appearance of unsafe sexual practices in the era of potent anti-retroviral drugs. We describe a repeated import of syphilis by a couple of men-who-have-sex-with-men from Thailand to Czech Republic likely due to non-adherence of the patients to physician recommendations. Such cases can become foci for dissemination of once locally rare infections and present a danger for the community.

Prevalence of hepatitis C virus in adult population in the Czech Republic – time for birth cohort screening

Chronic hepatitis C is curable disease. Low detection rate could be one of the reasons of poor treatment uptake. It is important to identify HCV prevalence and anti-hepatitis C virus (HCV) positive patients in population by effective screening strategy such as risk-based or birth cohort screening programs. There are no national population-based estimates of the HCV prevalence in the Czech Republic (CZ). The most recent seroprevalence survey determined a prevalence of positive anti-HCV antibodies of 0.2% (in 2001). The aim of the study was to determine the seroprevalence of HCV, HCV viraemia and HCV genotype in the CZ adult population. We also estimated the number of persons living with chronic hepatitis C in CZ. The examined group included 3000 adults, 18–90 years of age enrolled in 2015. All serum samples were examined to determined anti-HCV antibodies positivity, HCV-RNA positivity and genotypes. Of the 3000 samples, 50 were found to be anti-HCV-positive, for a seroprevalence of 1.67% (2.39% in males, 0.98% in females). The overall prevalence of positive HCV RNA was 0.93%: 1.5% in males, 0.39% in females. HCV genotype (GT) 1a was determined in 25%, GT 1b in 25% and GT 3a in 46%. Since 2001, the HCV seroprevalence has increased 8-fold. The highest HCV seroprevalence occurred in males aged 30–44 years. We can estimate that there are more than 140,000 people with HCV antibodies and more than 80,000 people with chronic hepatitis C living in the CZ. The introduction of birth cohort HCV screening could be beneficial for the country.

Effect of antiviral treatment of chronic hepatitis C on the frequency of regulatory T cells, T-cell activation, and serum levels of TGF-beta.

The aim was to analyze T‐regulatory cells (Tregs), activated CD8+ T cells, and transforming growth factor‐beta (TGF)‐β in hepatitis C patients. We enrolled 31 patients with chronic genotype 1 hepatitis C virus (HCV) infection, 30 seropositive persons with spontaneous HCV elimination, and 23 healthy volunteers. The patients were examined at the beginning of the interferon‐alpha (IFN‐α)‐based therapy (baseline) and at weeks 4 (W4) and 12 (W12) of the therapy. The percentage of Tregs and the expression of activation markers CD38 and HLA‐DR on CD8+ T cells were analyzed in the peripheral blood by flow cytometry. Serum levels of TGF‐β were measured in a multiplex assay using flow cytometry. The percentage of Tregs in patients was higher than in controls and seropositive persons. Similarly, the percentage of CD8+ T cells expressing CD38 and HLA‐DR was higher in patients compared with controls and seropositive persons. Chronic HCV infection is associated with elevated circulating Tregs and activated CD8+ T cells. During IFN‐α‐based therapy these cells gradually increase, whereas TGF‐β serum levels decrease.

GENOTYPING OF VARICELLA-ZOSTER VIRUS (VZV) WILD-TYPE STRAINS ISOLATED IN THE CZECH REPUBLIC

OBJECTIVES Monitoring of the varicella-zoster virus is becoming an important tool for analysis of the circulation of individual strains of VZV which differ not only at the genomic level, but show a variability in their clinical and epidemiological characteristics. Such data are not available on a large scale from the Czech population and could help understanding the epidemiological and evolutionary characteristics of the virus, as well as its potential for reinfection and increased pathogenesis in the population groups at higher risk for complications. The main aim of this study was detection and monitoring of wild-type or vaccine VZV strain isolates in the region of Eastern Bohemia and genotypic characterization of these isolates. MATERIAL A total of 273 clinical samples were obtained from patients exhibiting symptoms of varicella zoster virus (VZV) infection manifested as chickenpox or herpes zoster (HZ) treated in the Faculty Hospital of Charles University, Medical School in Hradec Kralove, Czech Republic. METHODS Characterization of individual short VZV DNA sequences was performed utilizing restriction fragment length polymorphisms (RFLPs), PCR and sequencing. Single nucleotide polymorphisms (SNP) in open reading frames (ORF) 21, 22 and 50 were used to identify individual VZV strains. RESULTS All clinical isolates (97 from varicella, 176 from herpes zoster) were VZV positive wild-type strains. Sequencing analysis showed that 89 isolates were of the European E1 genotype, 180 were of the European E2 genotype and 2 were identified as the Mosaic M1 strain. In addition, for the first time in this region two unusual genotypes were identified, both representing a combination of E1 and M2 strain specific SNPs. CONCLUSION Our prospective VZV genotyping study which is the first to monitor the VZV epidemiological situation in the Czech Republic using such a large set of clinical specimens, has provided valuable epidemiological data and identified two unique VZV recombinants.

Tick-borne encephalitis virus - a rare cause of encephalitis in infants.

tick borne encephalitis (TBE) occurs most commonly in Central and Eastern Europe and Northern Asia. Genotypisation distinguishes between three subtypes – European, Siberian and Far Eastern, which are based on their geographical distribution [1]. Data of the Czech National Institute of Public Health (SZU ČR) show that 546 cases were reported in 2007, 25 per cent of which were children – but nonetheless, the incidence in the age group is merely 4.2/100,000 children [2]. A previously healthy three-month-old boy was admitted to the pediatric department of the regional hospital, having developed tonic-clonic seizures with a subsequent rise in temperature to over 38.5 °C. The boy’s mother reported that seven days before the clinical symptoms the child had been bitten by a tick that she had removed by herself, and no other medical measures had been taken. Due to repeated seizures the infant was transferred to the infectious diseases department of the University Hospital Hradec Králové for further specialized care. On admission the infant was somnolent, with sufficient spontaneous respiratory activity and positive signs of meningeal irritation. In the course of treatment with benzodiazepines, the spastic activity disappeared and no other anticonvulsive medication had to be administered. A lymphocytal pleocytosis (354/3 lymphocytes, 30/3 neutrophils), increased level of proteins 1,8 g/l and a normal glucose level were detected in the cerebrospinal fluid examination. All laboratory examinations which focused on the other most frequently occurring bacterias and neurotropic viruses (bacterial cultures, PCR – Herpes simplex, H. zoster, Enteroviruses, Listeria monocytogenes, Borrelia burgdorferi) were negative. The examination of antibodies against TBE by means of the ELISA method was positive in the IgM class, both in serum and in CSF, and negative in the IgG class. The further clinical course of the disease was surprisingly favourable – in the course of three days the temperature dropped, the child started to react normally, and the anticonvulsive therapy was gradually discontinued. The EEG recording only contained minute non-specific patterns. Before the infant’s discharging the cerebrospinal fluid revealed a substantial decrease of lymphocytes and neutrophils (30/3, 5/3). Three months after the acute phase, MRI of the brain resulted in normal findings with no organic alterations in brain tissue, and even observations lasting over a period of a year revealed no alterations in psychomotor development. Seroconversion of the infant’s serum with the onset of IgG and disappearing IgM antibodies against the TBE virus confirmed the diagnosis, the mother’s antibodies being negative in both classes. The most common clinical TBE forms in children include acute meningitis or meningoencephalitis, while serious bulbo-cervical forms are, unlike in adults, extremely rare [3]. The prognosis of TBE in children is generally good, too, with the exception of rare secondary epilepsy cases, and a few fatal cases described in literature [4]. The presented case is the first of its kind in the Czech Republic, and only a few similar cases can be found in the literature over the last 14 years [5–7]. The overall numbers of TBE cases in children vary considerably in individual European countries which also explains the different vaccination strategies. Austria introduced a massive vaccination campaign in 1981. Up to that time, around 500 TBE cases were reported every year (ranging from 280 to 700). In 1982 the number of cases started to decrease sharply, reaching 54 in 2004 [8]. In addition, in 1984 the national recommendation was extended to all children over one year of age who are living or travelling to endemic areas – unlike other European countries. It becomes obvious from the above that thanks to the national vaccination programme started in the late 1970s, the incidence dropped to less than 1/100 000 and that the degree of vaccination increased to approximately 86 per cent [9]. In comparison with this, the current vaccination recommendations in the Czech Republic focused on children have not been officially laid down yet, although approximately 130 cases of the illness are reported annually. The vaccination coverage in the population is estimated to be over 11 per cent [2]. The post-exposure prophylaxis by a specific Ig, which was recommended formerly, is not acknowledged in European countries for safety reasons and its production has been stopped. The only possible, however, not entirely reliable protection for children in the Czech Republic below the age of one year is using suitable repellents, wearing appropriate clothes and abstaining from unpasteurised milk, because vaccination against TBE is not approved under the age of one. In Austria it is recommended to vaccinate children after the sixth months of life, if there is a special high risk.

EVIDENCE CELOROČNÍHO VÝSKYTU GENOTYPIZOVANÝCH DIVOKÝCH KMENŮ VARICELLA ZOSTER VIRU (VZV) U DĚTÍ A DOSPĚLÝCH V KLIMATICKÝCH PODMÍNKÁCH MÍRNÉHO PÁSU ČESKÉ REPUBLIKY

1 Katedra epidemiologie, Fakulta vojenského zdravotnictví, Univerzita obrany, Hradec Králové 2 Klinika nemocí kožních a pohlavních, Fakultní nemocnice Hradec Králové 3 Klinika infekčních nemocí, Lékařská fakulta Univerzity Karlovy a Fakultní nemocnice Hradec Králové 4 Přírodovědecká fakulta, Univerzita Hradec Králové 5 Centrum pro základní a aplikovaný výzkum, Fakulta informatiky a managementu, Univerzita Hradec Králové 6 Katedra organizace vojenského zdravotnictví a managementu, Fakulta vojenského zdravotnictví, Univerzita obrany, Hradec Králové

Invasive primary intracerebral infections in women caused by Streptococcus intermedius manifesting as purulent meningitis and intracerebral abscess

Invazivní primarně intracerebrální infekce u žen způsobené Streptococcus intermedius a manifestující se jako purulentní meningitida a intracerebrální absces The authors declare they have no potential con fl icts of interest concerning drugs, products, or services used in the study. Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy. The Editorial Board declares that the manu script met the ICMJE “uniform requirements” for biomedical papers. Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.

AN UNUSUAL CASE OF MULTI-RECURRENT HERPES ZOSTER (HZ): A CASE REPORT

AIMS We report a case of multi-recurrent herpes zoster in a 53-year-old Caucasian woman treated repeatedly at the Faculty Hospital Hradec Kralove, Czech Republic over the years 2009 - 2011. METHODS Specific PCR methods targeting single nucleotide polymorphisms (SNPs) in open reading frames (ORF) 38, 54 and 62 were utilized to determine vaccine or wild type varicella-zoster (VZV) strains followed by SNPs analysis using two amplicons in ORF 22 and/or ORF 21/ORF 50. Additional genotyping in ORF 1, 6, 9 and 28 was subsequently performed due to the unusual results. RESULTS Three sets of clinical specimens from one patient (from hospital visits 2, 3 and 4) were analyzed and the presence of an unusual wild-type strain of VZV was discovered. The VZV strain isolated from the lesions bears a combination of markers characteristic both for Mosaic 2 (M2) and European 1 (E1) wild-type VZV strains. CONCLUSION This is the first report of atypical wild-type VZV strain circulating currently in Czech Republic.