Kathrine Stene-Johansen

Characterisation of an epidemic of hepatitis A virus involving intravenous drug abusers--infection by needle sharing?

An epidemic of hepatitis A virus (HAV) among intravenous drug abusers in Oslo involved 144 serologically confirmed cases. Another 26 patients (non‐drug abusers), of whom 14 were derived from a single nosocomial outbreak, were associated with the epidemic. Sequencing of the VP1/P2A junction revealed that viruses associated with the epidemic were completely identical, whereas other HAV samples collected during the same period differed by up to 10 %. HAV was detected in the serum of 48 of 100 patients by a nested PCR. Viremia was observed as early as 25 days before the onset of clinical hepatitis, and up to 30 days after. The large number of patients within the drug abuser group, and the few secondary cases, raised the question of whether the virus could be transmitted by the use of needles. To establish whether viral contamination of drugs did contribute appreciably to maintaining the epidemic, we examined heroin and amphetamine confiscated during the period, using immunomagnetic separation coupled to nested PCR, but failed to detect any virus. Antibodies against hepatitis B virus and hepatitis C virus were common among the HAV infected drug abusers (43% and 81%, respectively), suggesting widespread sharing of needles. This observation and the large number of patients with a demonstrable viremia suggest that needle sharing may contribute to the dissemination of HAV. J. Med. Virol. 53:69–75, 1997.

Large and prolonged food-borne multistate hepatitis A outbreak in Europe associated with consumption of frozen berries, 2013 to 2014.

In May 2013, Italy declared a national outbreak of hepatitis A, which also affected several foreign tourists who had recently visited the country. Molecular investigations identified some cases as infected with an identical strain of hepatitis A virus subgenotype IA. After additional European Union/European Economic Area (EU/EEA) countries reported locally acquired and travel-related cases associated with the same outbreak, an international outbreak investigation team was convened, a European outbreak case definition was issued and harmonisation of the national epidemiological and microbiological investigations was encouraged. From January 2013 to August 2014, 1,589 hepatitis A cases were reported associated with the multistate outbreak; 1,102 (70%) of the cases were hospitalised for a median time of six days; two related deaths were reported. Epidemiological and microbiological investigations implicated mixed frozen berries as the vehicle of infection of the outbreak. In order to control the spread of the outbreak, suspected or contaminated food batches were recalled, the public was recommended to heat-treat berries, and post-exposure prophylaxis of contacts was performed. The outbreak highlighted how large food-borne hepatitis A outbreaks may affect the increasingly susceptible EU/EEA general population and how, with the growing international food trade, frozen berries are a potential high-risk food.

Ongoing multi-strain food-borne hepatitis A outbreak with frozen berries as suspected vehicle: four Nordic countries affected, October 2012 to April 2013.

A food-borne outbreak of hepatitis A in Denmark was notified to other countries on 1 March 2013. A case-control study identified frozen berries eaten in smoothies as potential vehicle. In the following weeks, Finland, Norway and Sweden also identified an increased number of hepatitis A patients without travel history. Most cases reported having eaten frozen berries at the time of exposure. By 17 April, 71 cases were notified in the four countries. No specific type of berry, brand or origin of berries has yet been identified. .

Sensitive detection of human Caliciviridae by RT-PCR

A semi‐nested reverse transcriptase‐polymerase chain reaction (RT‐PCR) was developed for the detection of human Caliciviridae. The method was evaluated on faecal samples from patients with gastroenteritis sent to the Norwegian National Institute of Public Health for routine diagnosis by direct electron microscopy (EM). Of 166 samples, 49 were found to contain Caliciviridae by EM, while 7 samples contained other viruses. A total of 74 samples was positive by PCR, including all the samples with EM detectable Caliciviridae, while specimens containing other agents were negative. Phylogenetic analysis of RNA sequences from 14 Norwegian samples indicated that the viruses present in Norway are evenly distributed when compared to sequences of human Caliciviridae from other countries. The PCR primers should therefore be useful for samples from other regions. The phylogenetic analysis did not cluster viruses with a calici‐like morphology, but mingled them with sequences from Norwalk‐like viruses, indicating that the two morphological types do not represent separate genogroups.

Ongoing hepatitis A outbreak in Europe 2013 to 2014: imported berry mix cake suspected to be the source of infection in Norway

On 7 March 2014, an increase in hepatitis A virus (HAV) infections was identified in Norway. As of 12 April, 19 cases of HAV infection with a virus strain identical to an ongoing European outbreak have been identified. Six probable cases are currently under investigation. On 11 April, a frozen berry mix cake imported from another European country was found as the likely source of the outbreak; the importer has withdrawn the product in Norway.

Combined Analysis of the Prevalence of drug Resistant Hepatitis B Virus in antiviral therapy Experienced patients in Europe (CAPRE)

BACKGROUND European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. METHODS A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. RESULTS Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P < .001). CONCLUSIONS These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.

A Public Health initiative on hepatitis E virus epidemiology, safety and control in Portugal - study protocol

BackgroundThe discovery of autochthonous hepatitis E in industrialized countries has changed the understanding of hepatitis E virus (HEV) infection in these regions, now known to be mainly due to zoonotic transmission of genotype 3. The foodborne route of transmission via consumption of contaminated meat from HEV infected pigs is well documented as well as the direct occupational exposure to animal reservoirs. Accumulating evidence also points to an emerging potential threat to blood safety after the identification of viremic blood donors and the documentation of HEV-contaminated blood or blood products. Moreover, the origin of several iatrogenic cases remains unclear and porcine-derived pharmaceutic products have been suspected as a cause. Severe morbidity following HEV infection in patients receiving immunosuppressive therapy and in those with severe immunodeficiency from other causes has been recently recognized as a serious consequence of this infection in industrialized countries. In Portugal no large-scale HEV seroprevalence study has been undertaken, no professional risk groups have been identified, and the risk of blood donation from HEV silent infected donors is unknown. The present paper describes seroepidemiological and molecular approaches to answer these questions.Methods/designTo address these issues a study protocol was designed that will approach: i) the seroprevalence of HEV among the Portuguese general population; ii) HEV infection among butchers and slaughterhouse workers (occupational risk); iii) the silent HEV infection in Portuguese blood donors (HEV transfusion-associated risk); iv) the potential HEV contamination of porcine-derived pharmaceutical products. Commercial enzyme immunoassays and real-time/conventional RT-PCR assays will be used.DiscussionThis study is the first evaluation of the seroepidemiological status to HEV infection of the Portuguese population, the first to potentially identify professional risk groups, and to evaluate the safety of blood and blood products and porcine-derived pharmaceutics in Portugal. It will generate valuable data applicable for preventive and control measures against HEV infection (e.g., introduction of systematic screening of blood donors, control of blood products or porcine derived pharmaceutical products), thus helping to manage the burden of this viral disease.

Dry Blood Spots a Reliable Method for Measurement of Hepatitis B Viral Load in Resource-Limited Settings.

Background & Aims Hepatitis B virus (HBV) quantification is essential in the management of chronic hepatitis B, both to determine treatment eligibility and in the monitoring of treatment effect. This test, however, is rarely available in resource-limited settings due to high costs and stringent requirements for shipment and storage of plasma. Dried Blood Spots (DBS) can be a convenient alternative to plasma, but its use for HBV monitoring has not been investigated under real-life conditions in Africa. Methods The performance of DBS in HBV quantification was investigated using a modified commercial test (Abbott RealTime HBV assay). Paired DBS and plasma samples were collected from an HBV positive cohort in Addis Ababa, Ethiopia. DBS were stored at ambient temperature for 4–39 days before shipment to the laboratory. Results Twenty-six paired samples were selected covering the total range of quantification, from 2.14 log IU/ml to >7 log IU/ml. HBV was detected in 21 of 21 (100%) DBS from patients with a corresponding plasma viral load above 2.70 log IU/ml. The mean difference between plasma and DBS was 0.59 log IU/ml, and the correlation was strong (R2 = 0.92). In stability studies there was no significant change in DBS viral load after storage at room temperature for up to 12 weeks. Conclusions This study suggests that DBS can be a feasible and reliable alternative to plasma for quantification of HBV in resource-limited settings. DBS can expand access to antiviral treatment for patients in low- and middle-income countries.

Importance of molecular typing in confirmation of the source of a national hepatitis A virus outbreak in Norway and the detection of a related cluster in Germany.

In March 2014, after an increase of notifications of domestically acquired hepatitis A virus infections, an outbreak investigation was launched in Norway. Sequenced-based typing results showed that these cases were associated with a strain that was identical to one causing an ongoing multinational outbreak in Europe linked to frozen mixed berries. Thirty-three confirmed cases with the outbreak strain were notified in Norway from November 2013 to June 2014. Epidemiological evidence and trace-back investigations linked the outbreak to the consumption of a berry mix cake. Identification of the hepatitis A virus outbreak strain in berries from one of the implicated cakes confirmed the cake to be the source. Subsequently, a cluster in Germany linked to the cake was also identified.

Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia

Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub‐Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia.