Community outbreak of hepatitis A disproportionately affecting men who have sex with men in Toronto, Canada, January 2017-November 2018.

BACKGROUND: In late 2016 and early 2017, a number of countries began reporting hepatitis A virus (HAV) outbreaks involving person-to-person transmission among men who have sex with men (MSM), people using illicit drugs and homeless or underhoused persons. OBJECTIVE: To describe the epidemiology and public health response to an outbreak of HAV disproportionately affecting MSM in Toronto, Canada from January 2017 to November 2018. METHODS: Following an increase in the number of cases of HAV in MSM being reported in other countries, enhanced surveillance was performed for all non-travel-related cases of HAV reported from June 1, 2017 to November 1, 2018, including a retrospective analysis of cases reported from January 2017 to June 2017. Descriptive analysis and viral sequencing were performed to describe person-to-person transmission patterns and target interventions. Control strategies included interventions to promote the uptake of preexposure HAV vaccination, including social media campaigns geared to MSM, messaging to healthcare providers and vaccine clinics. RESULTS: Based on the outbreak case definitions, 52 confirmed and probable cases of HAV were identified. Over 80% of outbreak cases were male (n=43/52) and, among those for whom data were available, 64% (n=25/39) reported an MSM exposure. Data on hospitalization was available for 51 cases; 56% of confirmed cases (n=23/41) and 40% of probable cases (n=4/10) required hospitalization. Of the cases with serum samples that had HAV sequencing, 83% (n=30/36) had one of the three strains seen circulating in outbreaks among MSM internationally; 72% (n=26/36) were VRD_521_2016, which had been detected in recently reported European outbreaks among MSM. Targeted promotion of publicly-funded vaccination using social media platforms popular with MSM and targeted vaccine clinics were developed to promote HAV awareness and vaccine uptake among MSM. CONCLUSION: Outbreaks of HAV, attributed to person-to-person transmission of strains of HAV that disproportionately affected MSM and were likely to have been imported from international MSM outbreaks, have now occurred in Canada. Genetic sequencing of HAV, risk factor analysis of cases, monitoring trends of vaccine coverage in high-risk groups and initiation of vaccination campaigns that address barriers to HAV preexposure vaccine coverage in the MSM population may prevent future outbreaks.

Hepatitis E Virus Seroprevalence in Free-Ranging Deer in Canada.

Hepatitis E virus infection (HEV) is an important public health concern not only in traditional endemic areas, but also in some industrialized countries where both domesticated and wild animals have been recognized as potential zoonotic reservoirs implicated in HEV transmission. While the prevalence of infection in the deer population in Europe and Asia has been thoroughly investigated, it remains largely undetermined in North America. We assessed the presence of HEV in three different species of free-range deer in Canada. The seroprevalence of HEV among deer in Canada was 8.8% in white-tailed deer, 4.5% in mule deer and 3.2% in caribou. Hepatitis E virus RNA was not detected. Overall, data indicate that HEV infection occurs in deer in Canada. The absence of viraemia and the low seroprevalence especially in barren-ground caribou which is an important part of the diet in many northern communities suggests that the risk of zoonotic transmission may be less pronounced compared to other countries.

Hepatitis A virus infection associated with cannabis use.

We identified a case of acute Hepatitis A virus (HAV) infection linked to cannabis use. The local Public Health department received report of a man in his mid-20s with a classic presentation of hepatitis - jaundice, abdominal pain, vomiting, general malaise, and dark urine - as well as elevated serum aminotransferase levels and a positive anti-HAV IgM. Upon questioning, he reported no contact with ill individuals, or travel outside his metropolitan area. His exclusive source of water was the local municipal supply. He reported consuming mainly pre-packaged lower risk foods from large chain-style supermarket stores and eating at several local restaurants. While administering the questionnaire, the investigator identified that the patient smoked cannabis. Upon request, the patient agreed to provide a sample of cannabis for testing purposes. A viral elution of fresh cannabis leaves was completed. The sequences derived from the patient's serum sample and the eluate from the cannabis leaves were identical, but did not match any other HAV sub-genotype 1B sequences from Canadian isolates within the National Microbiology Laboratory database. Hepatitis A virus can survive >60 days when dried and kept at room temperature and low humidity; HAV can remain infectious in water at room temperature for 300 days. It cannot be concluded with certainty that the cannabis was the source of the hepatitis A; however, as other sources were excluded, or were of lesser probability, the association of cannabis with his disease acquisition remains strong.

Outbreak of acute hepatitis B virus infection associated with exposure to acupuncture.

BACKGROUND: The most common risk factors for acute hepatitis B virus (HBV) infection are sexual contact, injection drug use and perinatal, or nosocomial exposure. Acupuncture, used in China for over 2,500 years, has been gaining popularity as an alternative medical therapy in the western world, but when associated with poor infection control practices, is also a risk for blood-borne infections. OBJECTIVE: To describe the outbreak investigation following detection of two cases of acute HBV infection associated with acupuncture services from the same provider within four months of symptom onset. METHODS: The outbreak investigation included genotyping of HBV from the identified cases, on-site assessment of the acupuncturist's infection prevention and control practices and chart review of known clients. RESULTS: Both cases had HBV genotype D1 with an identical fingerprint and both clients had visited the clinic on the same day denying other recent risk exposures. Inspection of the acupuncturist's practice revealed high-risk re-use and inappropriate storage of disposable needles. The Regional Health Authority ordered cessation of clinic practice until infection control measures were remediated. A public service announcement and mailed notifications to clients identified from practitioner records recommended that all clients be tested for HBV, human immunodeficiency virus (HIV) and hepatitis C. CONCLUSIONS: A clear epidemiological linkage of these two acute HBV infections to the same acupuncture clinic, evidence of substandard infection control practice in the clinic and identical HBV molecular and genotypic profiles of the two cases are highly suggestive that contaminated acupuncture needles likely resulted in at least two cases of acute HBV infection. This is the first known reported transmission of HBV from acupuncturists re-use of disposable needles and the first HBV outbreak associated with exposure to acupuncture reported this century in an industrialized country. Increased provider oversight and patient education may prevent future outbreaks.

Serological and molecular evidence of a plausible transmission of hepatitis E virus through pooled plasma.

BACKGROUND AND OBJECTIVES: Recently, hepatitis E virus has been recognized as a new transfusion-associated risk; however, its efficiency of transmission through blood products requires further investigation. Asymptomatic viremia of short duration has been observed in blood donors from several European countries to the rate of <1:10,000 and HEV transmission in recipients of blood products has been documented in Japan and Europe. Although HEV RNA was detected in large plasma fractionation pools used for manufacturing of plasma derived products, HEV transmission has not been demonstrated so far. In this study, we investigated the possibility of HEV transmission in patients with thrombotic thrombocytopenic purpura whose treatment included up to 40 l of plasma exchange. MATERIALS AND METHODS: Thirty-six TTP patients received either solvent-detergent-treated plasma prepared by pooling of 2500 single-donor or cryosupernatant plasma. Three samples were collected from TTP patients at time 0, 1 and 6 months post-treatment and tested for anti-HEV antibodies. Patients with HEV seroconversion were also tested for viremia by PCR. RESULTS: Two of seventeen TTP patients treated with SDP showed serological evidence of HEV infection. The 1-month samples from these patients were also positive for HEV RNA. A distinct rise of anti-HEV IgG level was detected in two other TTP patients with weak pre-existing immunity to HEV; this observation is indicative of a possible immune response boost due to a breakthrough infection. CONCLUSION: This work provides, for the first time, indirect evidence of HEV transmission by pooled plasma and warrants further studies.

Hepatitis A outbreak in British Columbia, Canada: the roles of established surveillance, consumer loyalty cards and collaboration, February to May 2012.

Non-travel-related hepatitis A is rare in Canada. We describe a hepatitis A outbreak investigation in British Columbia in February to May 2012 in which exposure history was collected from nine confirmed non-travel-related cases. Suspected foods were tested for hepatitis A virus (HAV): a frozen fruit blend was identified as a common exposure for six of the nine cases using supermarket loyalty cards. Consumption of the product was confirmed in each case. Genetic analysis confirmed HAV genotype 1B in the six exposed cases. Of the three non-exposed cases, the virus could not be genotyped for two of them; the virus from the other case was found to be genotype 1A and this case was therefore not considered part of the outbreak. HAV was detected by PCR from pomegranate seeds, a component of the identified frozen fruit blend. Historically low levels of HAV infection in British Columbia triggered early recognition of the outbreak. Loyalty card histories facilitated product identification and a trace-back investigation implicated imported pomegranate seeds.

Distribution of Hepatitis C virus genotypes among newly acquired HCV infections in British Columbia (2000-2013).

BACKGROUND: Characterization of newly acquired Hepatitis C virus (HCV) infections is important in order to understand the epidemiology and spread of HCV. OBJECTIVE: To describe the Hepatitis C virus (HCV) genotype distribution of newly acquired HCV infections in the province of British Columbia for the period 2000-2013. METHODS: A descriptive cross-sectional analysis of multi-year data on HCV genotypes. Time trends for the proportion of different HCV genotypes are presented only for newly acquired (incident) HCV infections. RESULTS: For acute cases, genotype 1a remains the dominant HCV type in circulation (50%), followed by genotype 3a (34%). HCV genotype 1b declined, while genotype 2 was relatively stable. Phylogenetically-related clusters of HCV strains were observed indicating a common source of infection. CONCLUSION: Enhanced hepatitis surveillance provides a mechanism for monitoring different HCV strains currently circulating in the community. While HCV genotype 1a continues to be the most prevalent, changes in the relative frequency of genotypes 1 and 3 have been observed. This may have important implications for the control and prevention of the infection.

Genotype D amongst injection drug users with acute hepatitis B virus infection in British Columbia.

The eight genotypes of hepatitis B virus (HBV) exhibit distinct geographical distributions. This study identified HBV genotypes and transmission modes associated with acute infection in British Columbia (BC), Canada, from 2001 to 2005. Seventy cases of acute HBV in BC were identified from laboratory reports using a standardized case definition. Interviews for risk factors and hepatitis history were conducted for each case. HBV genotypes were determined by BLAST comparison analysis of the surface (S) or preS gene sequence. To illustrate the distribution of genotypes identified amongst acute cases in BC, an annotated map was produced showing the global occurrence of HBV genotypes. The majority of acute HBV cases occurred in Caucasian, Canadian-born males, with 30% of cases reporting injection drug use (IDU) and 21% reporting incarceration. The most common genotype observed was genotype D (62.9%), followed by genotypes A (18.6%), C (11.4%), B (4.3%), and E (1.4%). A significant association was observed between Genotype D and IDU (P = 0.0025) and previous incarceration (P = 0.0067). Phylogenetic analysis of the S gene sequence demonstrated identical or high genetic relatedness amongst genotype D viral strains (86% sub-genotype D3), thus verifying transmission clustering amongst BC injection drug users. The association between acute HBV genotype and reported transmission modes has not been previously described in North America. Tracking of genotypes can help identify disease transmission patterns and target at-risk populations for preventive immunization.

Incidence and risk factors for newly acquired hepatitis C virus infection among Aboriginal versus non-Aboriginal Canadians in six regions, 1999-2004.

The purpose of this study was to compare hepatitis C virus (HCV) incidence and recent patterns of transmission within Aboriginal and non-Aboriginal Canadians. Cases of newly acquired HCV infection (in patients > or =15 years) reported to the Enhanced Hepatitis Strain Surveillance System from six jurisdictions in Canada were analyzed. Information on demographic and clinical characteristics as well as risk factors for HCV infection was collected using standardized questionnaires. Univariate analysis showed Aboriginal patients to be significantly more likely than non-Aboriginal patients to report injection drug use (77.1% vs. 64.0%; p < 0.05), to be female (54.6% vs. 37.6%; p < 0.05), to report high-risk sexual behaviors (48.6% vs. 34.1%, p < 0.05), and to report drug snorting (45.7% vs. 32.7%, p < 0.05). The median age of Aboriginal patients was significantly younger than that of non-Aboriginal patients (31 years [range, 15-71] vs. 34 years [range, 15-81]; p < 0.05). The overall incidence of HCV infection per 100,000 people aged 15 years and older was 18.9 (95% confidence interval [CI] 15.5-23.1) in Aboriginal people and 2.8 (95%CI 2.6-3.1) in non-Aboriginal people. Poisson regression analysis revealed that Aboriginal Canadians were more likely than non-Aboriginal Canadians to develop acute hepatitis C (adjusted rate ratio 5.8, 95%CI 4.7-7.3). An appropriate and effective public health strategy that includes planned and implemented prevention programs in partnership with the Aboriginal community is needed.

Enhanced surveillance for childhood hepatitis B virus infection in Canada, 1999-2003.

Since hepatitis B virus (HBV) infection can have serious sequelae, especially if infection occurs during childhood, there is a continuing need to examine its epidemiology so as to inform control measures. We analyzed trends in disease incidence and patterns of hepatitis B virus (HBV) transmission in both Canadian-born and non-Canadian-born children from 1999 to 2003, through the Enhanced Hepatitis Strain Surveillance System. Amongst Canadian-born children, the incidence of newly identified HBV infection per 100,000 declined significantly during the study period from 1.4 in 1999, to 0.5 in 2003 (RR, 0.75 per year; 95% CI, 0.60-0.95). Amongst non-Canadian-born children, the incidence of HBV infection per 100,000 ranged from 9.4 to 16.3, during the study period (linear trend test, p=0.69). Poisson regression analysis revealed that non-Canadian-born children were more likely to have HBV infection (RR, 12.3; 95% CI, 7.6 to 19.8), than Canadian-born children. HBV infection was found to be more common among children emigrating from high endemic area, than among Canadian-born children. Current Canadian immunization policy should take into consideration the protection of all children against HBV infection, including those coming from countries where mass hepatitis B vaccination programs have still not been launched.

Comparison of six sets of PCR primers from two different genomic regions for amplification of GB virus C/hepatitis G virus RNA.

Forty-four clinical samples positive for GB virus C (GBV-C)/hepatitis G virus (HGV) were tested with six primer sets, four from the 5' untranslated region (5'-UTR) and two from the NS5a genomic region. Two of the 5'-UTR primer sets, when used in a single-round 60-cycle PCR, detected between 86.4 and 97.7% of the positive samples, while two different sets from the same area, when used in a nested PCR, amplified between 97.7 and 100% of the positive specimens. Both sets from the NS5a region, when used in a single-round PCR, detected 95.5% of the GBV-C/HGV-positive samples. Parallel testing with two PCR sets, one from the 5'-UTR and a second from NS5a, may eliminate false-negative results attributable to the genetic heterogeneity of the virus.

Subtyping of hepatitis C virus isolates by a line probe assay using hybridization.

A reverse hybridization test (Inno-LiPA HCV; Innogenetics, N.V., Zwijnaarde, Belgium) was used for typing hepatitis C virus. All 38 samples, typed by PCR with primers from core and NS5 genes, were also genotyped by this test. Of the samples, 33 (87%) had the same subtypes by both assays. The correlations between PCR and Inno-LiPA for individual types were 77% for type I (1a), 90% for type II (1b), 100% for type III (2a), 100% for type IV (2b), and 100% for type V (3a). One of the type III (2a) samples also reacted with type I (1a) probes in the Inno-LiPA test.

Genotyping of Canadian hepatitis C virus isolates by PCR.

We used PCR for hepatitis C virus (HCV) genotyping with type-specific primers from the core and NS5 genes. Type I was predominant in the general population (58% in blood donors) as well as in different risk groups, such as intravenous drug abusers (58%), blood transfusion recipients (64%), hemophiliacs (62%), and patients with HCV chronic liver disease (76%). Types II, III, and IV were less prevalent in Canada, being found in 10.92, 6.72, and 5.88% of the population, respectively. The type II core primer was not type specific and reacted with the majority of our type I HCV samples, suggesting a false-positive dual infection with two different genotypes (I and II). Digestion of these amplified type I and type II products with restriction endonuclease AccI proved to be very useful in the exclusion of false-positive dual type I and type II infections.

Detection of hepatitis C virus infection with recombinant immunoblot assay, synthetic immunoblot assay, and polymerase chain reaction.

The newly developed immunoblot assay, RIBA SIA (recombinant and synthetic polypeptide immunoblot assay), Chiron, Calif., was compared with the commercially available second generation recombinant immunoblot assay (RIBA-2) for the detection of antibody to hepatitis C virus (anti-HCV). The two immunoblot tests were also compared with the polymerase chain reaction (PCR) for the detection of HCV RNA. Ninety-one percent of samples reactive by RIBA-2 were positive for anti-HCV by RIBA SIA. A total of 31% of RIBA-2 indeterminate samples became reactive by RIBA SIA, 24% became non-reactive, and 45% remained the same. Samples reactive by RIBA-2 or SIA from different risk groups, were mostly positive (67-100%) by PCR for HCV RNA. All indeterminate samples from hemophiliacs and intravenous drug users were PCR positive. RIBA SIA is more sensitive and specific than RIBA-2 and correlates well with PCR results.

Effect of ribavirin on hepatitis A virus replication in vitro.

The effect of ribavirin on fetal Rhesus monkey kidney cells (FRhK-4) acutely or chronically infected with hepatitis A virus was studied. The effect of ribavirin on hepatitis A virus yield as detected by radioimmunoassay in acutely infected FRhK-4 cells was dependent on hepatitis A virus inoculum dose. Treatment with 100 µg/mL ribavirin completely inhibited hepatitis A virus growth in cultures infected with 100 to 800 tissue culture infectious dose 50 (TCID(50)) hepatitis A virus, but inocula of 800 to 1600 TCID(50) resulted in limited production of virus. The effect was time dependent and required more than 96 h of treatment to inhibit the virus completely. Ribavirin was less effective in treating cells persistently infected with hepatitis A virus, although there was significant inhibition of hepatitis A virus (82%) in persistently infected cells as well. Ribavirin had some inhibitory effect on cell growth; treatment with 25, 50 or 100 µg/mL ribavirin reduced cell growth by approximately 0, 20 and 40%, respectively.

[DNA, RNA and protein synthesis in hepatitis A virus-infected cells]. / Sintez DNK, RNK i belkov v kletkakh, zarazhennykh virusom gepatita A.

Synthesis of DNA, RNA, and protein macromolecules was observed in cells infected with a strain of HA virus which had undergone 11 passages in the same culture. At 24-hour intervals the infected and uninfected cells were pulse-labeled with 1 microCi/cc 3H-thymidine, 3H-uridine, and 14C-valine. In 6-9 days after cell inoculation, inhibition of DNA, RNA, and protein synthesis was observed, being most marked in DNA synthesis. The synthesis of these macromolecules increases on the 10-13th day which coincides with virus antigen accumulation in the cell cytoplasm.

[Comparative studies of the distribution of hepatitis B markers among blood donors and patients with post-transfusion hepatitis in the city of Sofia]. / Sravnitelni prouchvaniia vurkhu razprostranenieto na gepatitni B-markeri sred kruvodariteli i sred zaboleli ot posttransfuzionen khepatit v gr. Sofiia.

The incidence of HBsAg, anti-HBs, HBeAg and anti-HBe was studied in blood donor via various methods. HBsAg was established in 0.9 to 1.2% on the average among the blood donors paid; in 1.4 to 3.9% among the unpaid ones and 4.7 to 5.1% among the blood donors from organized population groups. Anti-HBs was established in 14.2%, HBeAg in 13.6% and anti-HBe in 38.2% from the HBsAg positive. With the comparative juxtaposition in the post-transfusion hepatitis (PTH) among the patients admitted to hospital for viral hepatitis a tendency was established to reduction from 0.9% for the period before the testing of the blood donors for HBsAg, 7.5% for the period tested by immunoelectrophoresis (IEP), and 4.5% for the period tested by reversal passive hemagglutination (RPHA). Patients HBsAg-positive were established by IEP in 39.2% on the average and by RPHA in 48.6%. A relative increase is reported of non-B PTH, non-A, non-B PTH in particular, with the introduction of more sensitive methods for investigations of blood donors for hepatitis B markers.