HEPATITIS A VIRUS : ITALIAN FROZEN BERRIES (redcurrent, black-,blue- raspberries)

HEPATITIS A - EU (05): (ITALY) FROZEN BERRIES ********************************************* A ProMED-mail post ProMED-mail is a program of the International Society for Infectious Diseases Date: Thu 4 Jul 2013 Source: Eurosurveillance Edition 2013, 18(27) [summ., edited] Ongoing outbreak of hepatitis A in Italy ---------------------------------------- [Byline: Rizzo C, Alfonsi V, Bruni R, Busani L, Ciccaglione AR, De Medici D, Di Pasquale S, Equestre M, Escher M, Montaño-Remacha MC, Scavia G, Taffon S, Carraro V, Franchini S, Natter B, Augschiller M, Tosti ME, the Central Task Force on Hepatitis] Since January 2013, an unusual increase in hepatitis A cases has been detected in northern Italy. A total number of 352 cases were reported to the integrated surveillance system between January 2013 and the end of May 2013, and this represents a 70 percent increase compared to the same period of the previous year [2012]. The outbreak is ongoing and the public health authorities are continuing their investigations to establish the transmission vehicle and to control the outbreak. From 1 Jan 2013 to 31 May 2013 a total of 352 cases of hepatitis A were reported to the Italian national surveillance system, corresponding to a 70 percent, 54 percent, and 34 percent increase in HAV [hepatitis A virus] notifications compared to the same period in 2012, 2011 and 2010, respectively. Here we describe the epidemiological features of the cases and the investigation of the outbreak. Surveillance of hepatitis A in Italy ------------------------------------ Hepatitis A is a notifiable disease in Italy. According to the national legislation, laboratory-confirmed cases of hepatitis A virus (HAV) infection are reported by clinicians to the local health units (LHUs) which are responsible for the epidemiological investigation. From the LHUs, notifications are sent to the regional health authorities (RHAs) and from here to the Ministry of Health. However, the routine notification system does not collect information on risk groups and risk factors associated with hepatitis A and there is an important delay in the transmission of the data [1]. For this reason, in 1984, a specific sentinel surveillance system for acute viral hepatitis (SEIEVA -- Sistema Epidemiologico Integrato Epatiti Virali Acute) was set up in parallel with the official notification system in Italy [2]. Data included in the SEIEVA system provide insight into the risk factors associated with the disease. Data collected by SEIEVA are provided by LHUs, which participate on a voluntary basis. A case is defined as a person with an acute illness including symptoms clinically compatible with hepatitis A, such as fever, fatigue, nausea, vomiting, abdominal pain, dark urine and jaundice, and positive for IgM anti-HAV. Cases are interviewed using a standardised online questionnaire collecting socio-demographic, clinical and laboratory information, and information on possible risk factors (shellfish consumption, contact with a jaundice case, travel to an endemic area, child attending daycare in the household, intravenous drug use in the last 6 months). After the alert issued by the northern European countries about a possible association between the hepatitis A cases and frozen berries [3], the consumption of mixed frozen berries was included as another possible risk factor in the SEIEVA questionnaire at the end of April 2013. As of 31 May 2013, 76 percent of the Italian LHUs (139/181) participate in the SEIEVA. The participating LHUs are distributed all over the country and cover 70 percent of the population. Data were adjusted considering the total population of the LHUs' catchment areas. Epidemiological situation of hepatitis A in Italy ------------------------------------------------- In recent decades, the epidemiological pattern of hepatitis A has changed. Italy is considered to be at low/intermediate endemicity for HAV [2,4]. The improved health and sanitary conditions have favored a progressive decrease of the infection rate in children, and a major shift of the population at risk, with the highest incidence reported in young adults. Outbreaks were described in 1996-1997 and 2004 mainly in southern Italian regions (Apulia and Campania) and were related to the consumption of contaminated raw shellfish [5,6]. From 1997, when the incidence was 19 per 100 000 population [2] to date, a decreasing trend in the incidence of HAV has been observed, to 1.1 cases, 0.7 and 0.8 per 100 000 population in 2010, 2011, and 2012, respectively [7]. The 2013 hepatitis A outbreak in Italy -------------------------------------- From 1 Jan 2013 to 31 May 2013 a total number of 352 cases of hepatitis A were reported to SEIEVA surveillance system, corresponding to a 70 percent, 54 percent and 34 percent increase in HAV notifications compared to the same period in 2012, 2011 and 2010, respectively. The highest increase in the number of cases was observed in 7 northern Italian regions (Trento and Bolzano, Emilia-Romagna, Lombardy, Friuli Venezia Giulia, Piedmont, and Veneto) that accounted for 193/352 (55 percent) of the total cases recorded in 2013. In these 7 regions, the cumulative incidence was 2.66 per 100 000 population in the 5-month reference period. Another region that showed an increase in the number of cases in 2013 is Apulia, in southern Italy, which recorded a 22 percent increase in the number of cases in 2013; 77 of the 352 cases were reported from this region. The mean age of cases was 35 years (range: 2-63 years) and the median was 39 years; 23 cases (12 percent) were recorded in children under 14 years. The cases were equally distributed among men and women: 55 percent of the cases were men and 45 percent were women. A total of 159 persons were hospitalised, with the majority of hospitalised cases in the age group of 35-54 years. As of 31 May 2013, no acute liver failures and deaths occurred; 4 cases had been vaccinated against hepatitis A, with one dose within the 3 weeks before the onset of symptoms, so these were not considered vaccine failures. With regard to the risk factors, among those who answered the questionnaire (193 cases), 3 percent (7/193) reported to have travelled to Egypt, 17 percent (33/193) reported to have eaten raw seafood and 20 percent (37/193) mixed berries in the 6 weeks before the symptom onset. When considering risk factors distribution after the end of April [2013] (date of introduction of the question on the consumption of frozen mixed berries), the majority of cases (37 of 46) reported having consumed frozen mixed berries. Description of the 2013 hepatitis A outbreak in the provinces of Trento and Bolzano --------------------------------------------------------------------------- In May 2013, Germany, the Netherlands and Poland reported through the Epidemic Intelligence Information System for food- and waterborne diseases (EPIS-FWD) and the Early Warning and Response System (EWRS) 15 cases of HAV infection associated with a ski holiday in the autonomous provinces of Trento and Bolzano (northern Italy). The sequencing of the VP1-region of these 5 Italian isolates, from Trento province, showed 100 percent nucleotides homology with those isolated from 2 German and one Dutch case [8]. After the EPIS and EWRS notifications, a retrospective epidemiological investigation started in the provinces of Trento and Bolzano, contacting cases notified through the regional notification system. For the epidemiological investigation, a confirmed case was defined as a person resident in the provinces of Trento and Bolzano with an acute illness including symptoms clinically compatible with hepatitis A, such as fever, fatigue, nausea, vomiting, abdominal pain, dark urine and jaundice, and identified as positive for IgM anti-HAV after 1 Jan 2013. Between 1 Jan and 31 May 2013, 31 cases of HAV infection were notified in the province of Trento (a 13-fold, 19-fold and 6-fold increase approximately, compared to the same period in 2012, 2011, and, 2010 respectively). The 1st case reported the onset of symptoms on 2 Feb 2013 and the most recent case was identified on 31 May 2013. Most of the cases had the onset of symptoms in May 2013 (15 cases). In the province of Bolzano, 7 cases were reported in the same period. The epidemic curve of the 38 confirmed HAV infection cases in these 2 provinces shows the evolution of the outbreak over time and suggests a common vehicle of transmission. In these 2 provinces, the mean age of the cases was 36.3 years (range: 3-63 years) and the median was 38.5 years. Men were more represented than women (24 versus 14). A total of 31 persons were hospitalised and the majority of them were 35 to 54 years old. There was only one case vaccinated and this case was reported from the province of Trento; however, this case had been vaccinated with one dose within the 3 weeks before the onset of symptoms, so this was not considered a vaccine failure. Preliminary epidemiological investigation for the identification of risk factors and common exposures focused on consumption of contaminated food as no epidemiological link between the cases could be confirmed. The only common food consumed by all cases was mixed berries or food containing mixed berries (cakes). Serum samples were collected during the acute phase of the disease from 5 of the 38 cases, all from the Trento province. The sequence of the VP1/2A region of the HAV 1A virus obtained from all of them (with GenBank accession number KF182323) showed a 100 percent nucleotides homology with sequences of the isolates from the German and Dutch cases. Investigation of food items implicated -------------------------------------- The preliminary epidemiological investigation in the provinces of Trento and Bolzano showed that the only common food consumed by different cases was mixed berries or food containing mixed berries (cakes). Moreover, the hypothesis was strongly supported by the results of an epidemiological investigation conducted in a family cluster in Veneto region. Part of the mixed berries (redcurrant, blackberries, raspberries, blueberries) that the cases indicated to have eaten within the period of time compatible with the onset of clinical symptoms were still available and were sampled. The analysis for HAV detection in the sample of mixed berries provided positive results. As a consequence, on 17 May 2013, the Italian Ministry of Health (which is the food safety authority at national level) communicated these findings through the European Rapid Alert System for Food and Feed (RASFF). Following these preliminary positive results, the surveillance of these food items was intensified. More samples of berries were collected throughout the country once they were identified as potential risk factors, and 2 sampled berries in Trento were found positive for HAV. On 30 May 2013, 2 additional RASFF notifications were issued to inform about new HAV findings in frozen mixed berries from Italy. Environmental investigations have been done on the mixed frozen berries suppliers of raw material in 6 different countries. Results on samples collected are pending at the time of the present rapid communication. Control measures ---------------- On 23 May 2013 the Ministry of Health (the General Direction for Prevention together with the food safety authority) published a note for RHAs in order to enhance surveillance and awareness of HAV recommending to report within 24 hours any new HAV cases, to collect additional epidemiological information on risk factors associated, and perform virus genotyping and sequencing from all new cases. In addition to the recommendation mentioned above, a case-control study in the regions that experienced the highest increase of cases was planned, in order to support the hypothesis of berries as a source of infection, to find other potential risk factors and to identify appropriate control measures. The National Institute of Health (Istituto Superiore di Sanita, ISS) is responsible for the coordination of the virological and epidemiological investigations, and of the case-control study. Moreover, after the positive results on the sampled frozen mixed berries from different regions, the Ministry of Health started the tracing back of this food item. The investigation identified a dealer that received consignments of berries from different countries (mix made in Italy, with raw material from Bulgaria, Canada, Poland, and Serbia). Following the RASFF notification from the Ministry of Health, regions recalled the lots that were identified positive for HAV and advised the population through the website of the Ministry of Health regarding the use of the leftover frozen mixed berries. Trace back investigations on food are ongoing for each new case notified. The European Centre for Disease Prevention and Control (ECDC) performed a rapid risk assessment that was published on 16 Apr 2013 [8]. Discussion ---------- Preliminary analysis of the case interviews on possible risk factors associated with the ongoing outbreak identified consumption of frozen mixed berries (redcurrant, blackberries, raspberries, blueberries) as a potential vehicle of infection. The hypothesis that they could be implicated is strongly supported by the detection of HAV virus in a sample of frozen mixed berries. The surveillance on these frozen mixed berries together with other food items potentially carrying the HAV (vegetables, seafood, and other food reported as potential risk factors by cases in the epidemiological investigation), has been intensified, to provide a clear picture of the distribution of the contaminated items and the risk of exposure through these. A total of 7 sequences of HAV genotype 1A isolated from cases in different countries (the Netherlands, Germany and Italy) and in different laboratories showed a 100 percent similarity. The genotype and the sequence of the virus isolated in the Italian outbreak is different from the currently ongoing outbreak with frozen berries as a suspected vehicle described in northern European countries and in the United States]. -- Communicated by: ProMED-mail [Remarkably, a 3rd outbreak of hepatitis A virus infection is described above to supplement the outbreaks in 4 Nordic countries of the European Union and several states in North America. Again, mixed frozen berries are implicated as the source of the outbreak. Hepatitis genotype 1a is implicated in the Italian outbreak in contrast to the Nordic countries and US outbreaks where the agent is hepatitis A virus genotype 1b. In contrast to the other 2 outbreaks, in the Italian outbreak hepatitis A virus was recovered directly from the frozen berries product. Frozen mixed berries are now being revealed as a previously unrecognised vehicle of hepatitis A virus infection. By their nature these soft fruits are frozen to enable them to be marketed far from their sites and time of production. The eastern Mediterranean region appears to be the source of at least some of these products. Harvesting berried soft fruits is a labour-intensive occupation which increases the risk of transmission of infectious agents. The habit of the mixing of different berried fruits increases the risk, since some fruits require a greater amount of handing than others. - Mod.CP A HealthMap/ProMED-mail map can be accessed at: .]