Ηepatitis A and enteric fever in Greece, 2004-2011: a cross-sectional analysis.

BACKGROUND: In Greece the number of international travellers has increased significantly the past decade. AIM: To study the impact of international travels on the epidemiology of hepatitis A and enteric fever in Greece. METHODS: We studied cases of hepatitis A and enteric fever notified through the National Surveillance System from January 1, 2004 through December 31, 2011. RESULTS: A total of 921 cases of hepatitis A and 106 cases of enteric fever were notified; of them, 88 (9.5%) and 46 (43.4%) were travel-associated, respectively. Travellers returning from Eastern Europe and the Middle East accounted for most imported cases of hepatitis A (37 (43.5%) and 14 (16.5%) cases, respectively). The Indian subcontinent was the prevalent area of acquisition of travel-associated enteric fever, followed by the Middle East (35 (83.3%) and 4 (9.5%) cases, respectively). Foreign-born travellers accounted for 43 (48.8%) and 39 (86.6%) cases of travel-associated hepatitis A and enteric fever, respectively. Children <15 years accounted for 65.1% of hepatitis A cases and 7.7% among foreign-born travellers. Greek Roma accounted for 270 (29.3%) of all hepatitis A cases notified. CONCLUSIONS: International travels have a significant impact on the epidemiology of enteric fever in Greece, affecting mainly foreign travellers. Hepatitis A carries a significant burden of morbidity among Greek travellers and children of foreign nationality. There is a need to improve travel medicine services for travellers travelling to developing countries.

Prevalence of leptospira in acute hepatitis syndrome and assessment of IL-8 and TNF-alpha level in leptospiral hepatitis.

To study the prevalence of leptospira in acute hepatitis syndrome and to assess interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha levels in the pathogenesis of hepatitis due to leptospiral infection. Two hundred and forty-seven consecutive cases with symptoms of acute hepatitis and 30 healthy controls were enrolled in the study and detailed clinical history was elicited from them. Enzyme-linked immunosorbent assays (ELISAs) for HAV, HBV, HCV and HEV were performed to rule out common viral aetiology of hepatitis. IgM antibodies to leptospira were detected by ELISA. IL-8 and TNF-alpha levels were estimated in leptospira-positive cases and healthy controls by ELISA. Out of 247 cases of acute hepatitis, 46 (18.62%) were observed to be positive for IgM antibodies for leptospira. The mean age of these patients was 31.99 ± 0.28 years (25 males and 21 females; M/F ratio: 1.19:1). The mean ALT, AST and ASP were raised in the majority of patients. IL-8 was found to be elevated (130.81 pg/ml) in a large majority of cases 41/46, 89.1% (P < 0.001). Patients with more severe symptoms were associated with higher levels of IL-8. One mortality was observed due to leptospira. Unpredictably, TNF-alpha level was largely suppressed (45.63 pg/ml) in most of the leptospira-positive patients in comparison with healthy controls. Leptospira-induced hepatitis should be actively looked for in patients negative for A-E viral hepatitis. IL-8 appears to play an important role in the pathogenesis of leptospiral hepatitis. High TNF-alpha should alert clinicians for aggressive in hospital management of patients.

Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis are prone to infection which is a frequent precipitant of hepatic encephalopathy (HE). Clinical studies have examined the importance of inflammation and infection in modulating the manifestation of symptoms of HE in acute liver failure and patients with cirrhosis and minimal/low grade HE. It would be logical to presume that this relationship persists in patients who develop severe HE in cirrhosis although this has not been examined to date. METHODS: We report the findings of a prospective audit of 100 consecutive patients with cirrhosis admitted between Jan 2000 and March 2008 to a liver Intensive Care Unit (ICU) where HE was the primary indication for admission (59% Grade 3; 41% Grade 4). Haematological and microbiological data were collected at ICU admission, and organ scores and outcomes were recorded. RESULTS: 46% of patients had positive cultures taken within ± 48h from admission to ICU [25% blood] and a further 22% were culture negative but had evidence of systemic inflammation (SIRS). SIRS score (p=0.03) and SOFA score (p=0.006) were significantly higher in those patients with Grade 4 HE, who were also less likely to survive (p<0.001). HE grade/coma score did not correlate with ammonia, biochemistry or MELD score. Fifty-two percent of patients survived their ICU stay while the remainder developed progressive multiorgan failure and died; 38% survived to discharge, and 16% were transplanted. CONCLUSIONS: These data support an association between infection/SIRS and not ammonia, in patients with cirrhosis that develop severe HE. The presence or absence of infection/SIRS did not determine survival.

Syphilis: an important cause of infectious hepatitis.

The UK incidence of infectious syphilis has risen sharply over the last 10 years; however, its diagnosis can be overlooked in patients who fail to disclose risk factors for its acquisition. This patient presented with hepatitis as part of a multisystemic illness and was investigated extensively before being diagnosed with secondary syphilis. The delay to diagnosis and treatment resulted in irreversible disablement. Syphilis should be considered in the differential diagnosis of hepatitis of uncertain aetiology. In addition, due to the similar presentation and risk factors for acquisition, we suggest that syphilis serology should be performed concomitant to all HIV tests, particularly those from outside the genitourinary medicine clinic setting.

Early disseminated borreliosis with multiple erythema migrans and elevated liver enzymes: case report and literature review.

A 69-year-old man presented with multiple livid maculae and infiltrated urticarial plaques, as well as elevated liver enzymes. Based on typical clinical picture, histopathology and positive PCR from a skin biopsy, we diagnosed an early disseminated infection with Borrelia afzelii presenting with multiple erythema migrans (erythemata migrantia) and a subclinical hepatitis. During antibiotic treatment with intravenous ceftriaxone, the maculae and plaques vanished almost completely and the liver enzymes decreased within 14 days. Dermatologists should keep in mind that early disseminated borreliosis can present with multiple erythema migrans and hepatitis.

Deep fungal dermatitis in three inland bearded dragons (Pogona vitticeps) caused by the Chrysosporium anamorph of Nannizziopsis vriesii.

The Chrysosporium anamorph of Nannizziopsis vriesii (CANV), a keratinophilic fungus that naturally and experimentally causes severe and often fatal dermatitis in multiple reptile species, was isolated in pure culture from skin samples of three inland bearded dragons (Pogona vitticeps) with deep granulomatous dermatomycosis. The first animal presented with a focal maxillary swelling involving the skin and gingiva. This lizard died while undergoing itraconazole and topical miconazole therapy. The second presented with focally extensive discoloration and thickening of the skin of the ventrum and was euthanized after 10 weeks of itraconazole therapy. A third lizard presented with hyperkeratotic exudative dermatitis on a markedly swollen forelimb. Amputation and itraconazole therapy resulted in a clinical cure. Histopathology of tissue biopsies in all cases demonstrated granulomatous dermatitis with intralesional hyphae morphologically consistent with those produced by the CANV. The second lizard also had granulomatous hepatitis with intralesional hyphae. Evidence in this report suggests that the CANV is the etiologic agent of an emerging condition in captive bearded dragons that has been called 'yellow fungus disease'.

Actualidad en hepatitis por virus A / Current situation in viral hepatitis A

La hepatitis por virus A (VHA) es una de las enfermedades más ampliamente difundidas en el mundo, generalmente aparece en forma de brotes epidémicos y se trasmite predominantemente por vía fecal oral, un tercio de los casos reportados por esta infección ocurre en niños y consta de varias formas clínicas de presentación; el tratamiento se basa en la aplicación de medidas generales así como la inmunoprofilaxis activa y pasiva, su elevada prevalencia en nuestro medio nos motiva a revisar la literatura reportada hasta hoy sobre el tema y resumir los aspectos más novedosos en cuanto a sus características y formas de evitarla.

[Prevention of acute enteric infections and viral hepatitis A appearing in connection with a natural disaster in the Republic of North Ossetia-Alana]. / Profilaktika ostrykh kishechnykh infektsii i virusnogo gepatitia A v sviazi s prirodnym stikhiinym bedstviem v Respublike Severnaia Osetiia-Alaniia.

Materials on the work of the sanitary and epidemiological service in the Republic of North Ossetia-Alania, aimed at the prophylaxis of acute enteric infections and viral hepatitis A under the conditions of the emergency situation caused natural calamities (inundation, high flood), are presented. The competent planning and operative realization of organizational, prophylactic and anti-epidemic measures have made it possible to keep morbidity in acute enteric infections and viral hepatitis A on a sporadic level.

Cholangiohepatitis and inflammatory bowel disease induced by a novel urease-negative Helicobacter species in A/J and Tac:ICR:HascidfRF mice.

Helicobacter bilis and H. hepaticus, both urease-positive intestinal helicobacters of mice, have been shown experimentally to induce proliferative typhlocolitis in scid mice. We recently isolated a urease-negative Helicobacter sp. (H. sp.) that also induced proliferative typhlocolitis in pilot studies in scid mice. To determine the pathogenic potential of H. sp. in immunocompromised and immunocompetent mice, 5-week old male A/J or Tac:Icr:Ha(ICR)-scidfRF mice were inoculated by intraperitoneal (IP) injection with approximately 3 x 10(7) colony-forming units (CFU) of H. sp. Mice were necropsied at various time points postinoculation (PI). Sham-inoculated mice had no clinical, gross, or histopathological lesions. In contrast, scid mice inoculated IP with H. sp. had severe hemorrhagic diarrhea and decreased weight gain at 2, 7, and 18 weeks postinoculation (PI), with severe proliferative typhlocolitis, phlebothrombosis, and hepatitis. A/J mice had no clinical signs, but had mild to moderate proliferative typhlocolitis and moderate to marked cholangiohepatitis at 7 and 24 weeks PI. A/J mice infected with H. sp. developed robust immune responses of a predominant Th1 type. This report demonstrates that infection with a urease-negative helicobacter can cause inflammatory bowel disease (IBD) and hepatitis in scid and immunocompetent A/J mice. These results provide a new model of IBD and cholangio-hepatitis associated with a specific urease-negative, novel H. species.

Study of transmission routes of Helicobacter pylori in relation to seroprevalence of hepatitis A virus.

The seroprevalence of Helicobacter pylori in a group of 1,043 healthy Japanese people was compared with that of hepatitis A virus (HAV), which was used as a marker of fecal-oral exposure. No statistically significant relationship was observed between seropositivity for HAV and that for H. pylori. Therefore, the fecal-oral spread of H. pylori is of limited relevance in Japan.

El espectro creciente de las hepatitis virales / The growing spectrum of viral hepatitis

El conocimiento de las hepatitis se remonta por lo menos al siglo VIII, pero éste ha avanzado vertiginosamente en los últimos 30 años gracias a factores como la aplicación de técnicas de inmunoquímica, microscopía electrónica, estudios epidemiológicos tanto clínicos como experimentales, técnicas de ingeniería genética, etc. Este trabajo revisa aspectos históricos de estas afecciones, las lateraciones histológicas hepáticas y manifestaciones clínicas que desencadenan. También describe las características principales de los virus A, B, C y E, la respuesta inmune que produce cada uno de ellos, su forma de infectar y la evolución, complicaciones y posibilidades de prevención de la enfermedad que desencadenan. Se comentan los resultados de los tratamientos con antivirales e interferón para las infecciones crónicas por virus B y C

Hepatitis A, B and C seroprevalence in Pakistan.

A cross sectional study was conducted to determine the seroprevalence of Hepatitis A, B, and C virus in healthy Pakistani children. HAV IgG antibody was assayed in 258 subjects and it was found that 94% children by 5 years of age had HAV IgG-antibody. The overall seroprevalence of HAV IgG antibody was 55.8% and IgM 5.3%. HBVsAb levels assayed in 236 healthy children showed a seroprevalence of 2.97%. Similarly, HCV antibody seroprevalence was found to be a low 0.44% in healthy children. HAV is a major cause of Hepatitis, as compared to HBV and HCV which are of low endemicity.

Rapid and efficient purification of hepatitis A virus from cell culture.

Hepatitis A virus (HAV) characteristically remains strongly cell-associated when grown in culture, with only small yields in the culture supernatant. Cell factories (6000 cm2) of BS-C-1 cells infected with the cytopathic HM175A.Z strain of HAV for 3, 4 or 7 days were harvested using trypsin to disperse the infected cell monolayer, and cells were collected by low speed centrifugation. More than 70% of the yield of virus and viral antigen can thus be obtained in the packed cell pellet. Packed cell pellets were resuspended in 5 volumes of isotonic buffer and cell membranes lysed by the addition of a non-ionic detergent. After removal of nuclei by centrifugation, ionic detergent was added to the clarified cytoplasmic extract. Under these conditions, HAV particles (virions and empty capsids) are the only particulate material remaining in the sample, and were recovered in a single ultracentrifugation step through discontinuous sucrose/glycerol density gradients. In one day, this method yields viral antigen with minimal cellular contaminants, in a concentrated volume suitable for subsequent biochemical, vaccine or diagnostic uses. The yield of viral antigen over numerous batches varied from 200 to 1600 vaccine-equivalent doses per cell factory, with a titre of up to 1 x 10(10) infectious particles per ml.

Infectivity titration of the fast-replicating and cytopathic hepatitis A virus strain HM175A.2 by an in situ enzyme immunoassay.

A simple, rapid and objective infectivity assay based on an in situ enzyme immunoassay (EIA) was developed for the fast-growing and cytopathic cell culture-adapted hepatitis A virus (HAV) strain HM175A.2. Infectivity titration by EIA correlated well with titration by cytopathic effects. The reliability of this assay was demonstrated by close agreement in virus infectivity titers among different assays of the same virus aliquot and between assays of different virus aliquots. HAV infected cell cultures after fixation could be stored for up to 1 week before testing without decline in virus titer.

[Experimental models of hepatitis A in macaques using viral strains isolated from man and monkeys]. / Eksperimental'nye modeli gepatita A na makakakh s ispol'zovaniem shtammov virusov, vydelennykh ot cheloveka i obez'ian.

Experimental hepatitis A (HA) models were obtained in macaca monkeys (15 M. fascicularis and 4 M. mulatta) by means of the strains of hepatitis A virus (HAV) isolated from the feces of a patient (HAV-H) and of spontaneously infected M. Mulatta (HAV-MM) and green monkeys Cercopithecus aethiops (HAV-CA). Irrespective of the strains used all seronegative macaca monkeys developed HA after intravenous-oral inoculation with the following patterns: elevation of the serum alanine aminotransferase level, HAV shedding in feces, seroconversion with the appearance of anti-HAV IgM and morphological changes in the liver characteristic of acute hepatitis. HAV in fecal samples and elevation of alanine aminotransferase were periodically detected. Periods of their discovery varied from 5-22 to 15-47 days and those of morphological changes in the liver from 9-24 to 40-83 days. The results of the experiments show that experimental HA models in Macaca monkeys are no less adequate than the previous ones developed in chimpanzees (Pan troglodytes), marmosets (Saguinus mystax) and owl monkeys (Aotus trivirgatus), but they are more readily available. Both strain HAV-H and strains from monkeys can be used for HA modelling. The models are expected to be used for studying yet unsolved problems of pathogenesis and immunogenesis, as well as for testing vaccines and antiviral drugs.

Sequence variability of hepatitis A virus and factor VIII associated hepatitis A infections in hemophilia patients in Europe. An update.

Outbreaks and sporadic cases of hepatitis A have been observed in 4 European countries in hemophilia patients receiving factor VIII preparations. PCR amplification of potential hepatitis A virus (HAV) nucleic acid present in plasma pools, purified factor VIII and acute-phase sera from infected individuals has been performed and the nucleic acid sequence determined for those samples that resulted in a positive PCR product. HAV sequences were detected in the serum of 2 German patients, but not in the factor VIII lots administered to these individuals. Screening of plasma pools and the corresponding 5 lots of factor VIII associated with the outbreak in Ireland did not reveal any HAV sequences. In contrast, a study of samples from Italy detected HAV sequences in 5 of 12 lots and in 2 hemophilia patients who developed hepatitis A. These data suggest that implicated factor VIII preparations might have been involved in the outbreaks of HAV infection among Italian hemophiliacs. However, no molecular evidence was obtained for a similar association in Germany or Ireland. The preliminary data from these two investigations must be verified by animal inoculation studies and supported by epidemiologic analysis.