Tick-borne Encephalitis Vaccine Failures: A 10-year Retrospective Study Supporting the Rationale for Adding an Extra Priming Dose in Individuals Starting at Age 50 Years.

BACKGROUND: Southern Sweden is endemic for tick-borne encephalitis (TBE), with Stockholm County as one of the high-risk areas. Our aim in this study was to describe cases of vaccine failures and to optimize future vaccination recommendations. METHODS: Patients with TBE were identified in the notification database at the Department of Communicable Disease Control and Prevention in Stockholm County during 2006-2015. Vaccine failure was defined as TBE despite adherence to the recommended vaccination schedule with at least 2 doses. Clinical data were extracted from medical records. RESULTS: A total of 1004 TBE cases were identified, 53 (5%) were defined as vaccine failures. In this latter group, the median age was 62 years (6-83). Forty-three (81%) patients were aged >50 years and 2 were children. Approximately half of the patients had comorbidities, with diseases affecting the immune system accounting for 26% of all cases. Vaccine failures following the third or fourth vaccine dose accounted for 36 (68%) of the patients. Severe and moderate TBE disease affected 81% of the cases. CONCLUSIONS: To our knowledge, this is the largest documented cohort of TBE vaccine failures. Vaccine failure after 5 TBE vaccine doses is rare. Our data provide rationale for adding an extra priming dose to those aged ≥50 years.

Secretor Status is Associated with Susceptibility to Disease in a Large GII.6 Norovirus Foodborne Outbreak.

Norovirus is commonly associated with food and waterborne outbreaks. Genetic susceptibility to norovirus is largely dependent on presence of histo-blood group antigens (HBGA), specifically ABO, secretor, and Lewis phenotypes. The aim of the study was to determine the association between HBGAs to norovirus susceptibility during a large norovirus foodborne outbreak linked to genotype GII.6 in an office-based company in Stockholm, Sweden, 2015. A two-episode outbreak with symptoms of diarrhea and vomiting occurred in 2015. An online questionnaire was sent to all 1109 employees that had worked during the first outbreak episode. Food and water samples were collected from in-house restaurant and tested for bacterial and viral pathogens. In addition, fecal samples were collected from 8 employees that had diarrhea. To investigate genetic susceptibility during the outbreak, 98 saliva samples were analyzed for ABO, secretor, and Lewis phenotypes using ELISA. A total of 542 of 1109 (49%) employees reported gastrointestinal symptoms. All 8 fecal samples tested positive for GII norovirus, which was also detected in coleslaw collected from the in-house restaurant. Eating at the in-house restaurant was significantly associated with risk of symptom development. Nucleotide sequencing was successful for 5/8 fecal samples and all belonged to the GII.6 genotype. HBGA characterization showed a strong secretor association to norovirus-related symptoms (P = 0.014). No association between norovirus disease and ABO phenotypes was observed. The result of this study shows that non-secretors were significantly less likely to report symptoms in a large foodborne outbreak linked to the emerging GII.6 norovirus strain.

Long-term follow-up of a vaccination program for infants born to HBsAg-positive mothers in Stockholm County, Sweden.

We investigated the long-term antibody response to hepatitis B virus (HBV) vaccination in babies born to chronically infected mothers. They received one dose of monovalent HBV vaccination at birth and one month of age, followed by 3 doses of hexavalent vaccine including an HBV component at ages 3, 5, and 12 months, respectively, with a very high percentage of protective anti-HBs levels at 13 months. At the age of 8-12 years, 56 out of 68 children (82%) had protective levels of anti-HBs, two had signs of anti-HBc seroconversion without any history of clinical disease and none had ongoing infection. A small subgroup was retested after one booster dose, in all resulting in increase in anti-HBs from below 10 IU/L to levels corresponding to protective immunity. We conclude that this vaccination strategy is effective throughout the first decade of life in avoiding chronic infection and in maintaining a good serological response.

Molecular characterization and epidemiological investigation of Cryptosporidium hominis IkA18G1 and C. hominis monkey genotype IiA17, two unusual subtypes diagnosed in Swedish patients.

Cryptosporidium hominis is considered a strictly human-adapted species, and it is only occasionally diagnosed in animals. However, two variants, C. hominis monkey genotype and C. hominis Ik, were originally described in non-human hosts, monkeys and horses, respectively. During a Swedish national Cryptosporidium study, where all samples were analyzed at the small subunit rRNA and the 60 kDa (gp60) glycoprotein loci, we identified two patients infected with C. hominis monkey genotype (subtype IiA17) and two infected with C. hominis subtype IkA18G1. The isolates were further analyzed at the actin and the 70 kDa heat shock protein loci, and these analyses showed that these two subtype families are closely related to each other and to human-adapted C. hominis as well as to Cryptosporidium cuniculus. The two patients with C. hominis monkey genotype infection (a father and son) had visited a monkey farm in Thailand prior to infection, while the two cases with C. hominis Ik were unrelated, both probably infected in Sweden. This is the first time that a monkey genotype infection in humans has been related to contact with monkeys and where the gp60 subtype was identified. It is also the first time that human infection caused by C. hominis subtype Ik is described. Even though we were not able to detect any parasites in the animal samples, zoonotic transmission cannot be ruled out in any of these cases because both subtype families are regarded as animal adapted.

Investigation of a food-borne outbreak of gastroenteritis in a school canteen revealed a variant of sapovirus genogroup V not detected by standard PCR, Sollentuna, Sweden, 2016.

A food-borne outbreak of gastroenteritis with more than 650 suspected cases occurred in April 2016 in Sollentuna, Sweden. It originated in a school kitchen serving a total of 2,700 meals daily. Initial microbiological testing (for Campylobacter, Salmonella, Shigella, Yersinia, Giardia, Cryptosporidium, Entamoeba histolytica, adeno-, astro-, noro-, rota- and sapovirus) of stool samples from 15 symptomatic cases was negative, despite a clinical presentation suggestive of calicivirus. Analyses of the findings from both the Sollentuna municipality environmental team and a web-based questionnaire suggested that the source of the outbreak was the salad buffet served on 20 April, although no specific food item could be identified. Subsequent electron microscopic examination of stool samples followed by whole genome sequencing revealed a variant of sapovirus genogroup V. The virus was not detected using standard PCR screening. This paper describes the epidemiological outbreak investigation and findings leading to the discovery.

Tick borne encephalitis (TBE)-vaccination coverage and analysis of variables associated with vaccination, Sweden.

To estimate the tick borne encephalitis (TBE)-vaccination coverage in the greater Stockholm region, we sent a questionnaire to a randomized sample of 8000 individuals in 2013. Fifty-three percent of all respondents (n=4307) reported being vaccinated against TBE at least once. Reasons for not vaccinating included: no perceived risk (28.6%), too expensive (25.6%), did not have the time or opportunity (23%) and worried about vaccine side-effects (20.5%). Multiple logistic regression revealed that the probability of being vaccinated was higher among those who reported ≥2 weeks outdoor exposure in a known high risk area (OR 4.13 95% CI 3.54-4.81) and in individuals ≥60 years of age compared to all other age groups (OR 0.67 95% CI 0.55-0.81). A high net household income was associated with a higher probability of being vaccinated (OR 2.10 95% CI 1.6-2.73). Being born outside Europe was negatively correlated (OR 0.57 95% CI 0.39-0.83). Based on our findings the estimated TBE-incidence in the unvaccinated regional population was 8.5-12/100,000 which is comparable with high endemic areas as the Baltic region and Central Europe. We suggest targeted vaccination and reimbursement strategies in high-endemic areas of Sweden. Our results indicate a need for improved public information about TBE.

Barriers to Trace-back in a Salad-associated EHEC Outbreak, Sweden, June 2013.

In June-July 2013, six counties notified the Swedish Institute for Communicable Disease Control of enterohaemorrhagic E.coli (EHEC) infections among attendees at a hotel in Dalarna, Sweden. An outbreak control team investigated to identify the source and implement control measures. We included individuals who attended the hotel between June 19th-25th in a cohort. We asked them about animal contact, swimming, and consumption of food items during this time using a questionnaire. A confirmed case was an EHEC O157:H7 outbreak strain positive individual who developed abdominal pain or diarrhoea between June 20th-July 2nd. We described the outbreak in time, place and person, calculated risk ratios (RR) and 95% confidence intervals (CI). We investigated the kitchen, tested and traced back implicated food items. 172 individuals responded. We identified 19 confirmed cases (Median age: 17 years, 64% female) with symptom onset between June 22nd-27th. Eating green salad on June 20th was associated with illness (RR:3.7;CI:1.3-11). The kitchen mixed green salads without records and destroyed leftovers immediately. Hence we could not conduct trace-back or obtain microbiological confirmation. Green salad contaminated before entering the kitchen was the likely outbreak source. We recommended early collaboration with food agencies and better restaurant records to facilitate future investigations.

Unusual cryptosporidiosis cases in Swedish patients: extended molecular characterization of Cryptosporidium viatorum and Cryptosporidium chipmunk genotype I.

Most human cases of cryptosporidiosis are caused by Cryptosporidium parvum or Cryptosporidium hominis, but the use of molecular diagnostic methods has revealed that several other less common species or genotypes can also be involved. Here, we describe two unusual causes of cryptosporidiosis, one being the recently described species Cryptosporidium viatorum and the other Cryptosporidium chipmunk genotype I. Two Swedish patients who were infected with C. viatorum had travelled to Kenya and Guatemala, respectively, and two others had been infected with Cryptosporidium chipmunk genotype I in Sweden. None of these four patients were immunocompromised, and all four showed classical symptoms of cryptosporidiosis. We performed extensive molecular characterization, including analysis of four loci. The two C. viatorum isolates were found to differ slightly at the 70-kDa heat shock protein locus, which may indicate a local geographical variation in this species that has previously been described exclusively on the Indian subcontinent.

Evaluation of a new vaccination program for infants born to HBsAg-positive mothers in Stockholm County.

To overcome previous shortcomings in the routines for prophylaxis to newborns of hepatitis B infected pregnant women, we established a new program in 2005. This program combined monovalent hepatitis B vaccine at birth and at one month with three doses of hexavalent vaccine, including a hepatitis B vaccine component, at 3, 5 and 12 months, respectively. The hexavalent vaccine and follow-up serologies were administered at the well baby clinics. Three hundred and eighty babies born to 356 HBsAg positive mothers (9% HBeAg positive), were evaluated. Twenty-two children were lost to follow-up, 329 of the remaining 358 children (92%) completed follow-up serology at ages 13-18 months, with protective anti-HBs levels in 99%. For comparison, in a previous cohort from 2000 to 2001, only 63% completed follow-up serology. We conclude that the adherence to the new program was good and that it resulted in a very high rate of protective antibody levels.

Zoonotic transmission of Cryptosporidium meleagridis on an organic Swedish farm.

We believe that we present the first evidence of zoonotic transmission of the bird parasite, Cryptosporidium meleagridis. Despite being the third most common cause of human cryptosporidiosis, an identified zoonotic source has not been reported to date. We found Cryptosporidium oocysts in pigs, sheep/goats, hens and broiler chickens on a farm with suspected zoonotic transmission. By DNA analysis we identified C. meleagridis in samples from one human, three chickens and one hen. Sequencing of the ssrRNA and 70kDa Heat Shock Protein (HSP) genes showed identical C. meleagridis sequences in the human and chicken samples, which is evidence of zoonotic transmission. The HSP70 sequence was unique.

Effectiveness of an adjuvanted monovalent vaccine against the 2009 pandemic strain of influenza A(H1N1)v, in Stockholm County, Sweden.

BACKGROUND: Vaccination against the pandemic influenza A(H1N1)v was performed in many countries during 2009, but population-based data on vaccine effectiveness are lacking. METHODS: We conducted a prospective cohort study involving all inhabitants in Stockholm County (n = 2,019,183) who were offered a monovalent AS03-adjuvanted influenza A(H1N1)v vaccine (Pandemrix, GSK), between 12 October and 31 December 2009. Overall vaccine coverage was 52%. A Web-based register with data on all vaccinated was linked by unique personal identification number to mandatory reports of influenza A(H1N1)v diagnoses. Vaccine failure was defined as a diagnosis or admission to hospital because of influenza >14 days after vaccination. Risk factors associated with vaccine failure were investigated by conditional stepwise logistic regression in a nested case-control study. The weekly incidence rate ratio for being diagnosed with influenza among vaccinated versus nonvaccinated persons was calculated. RESULTS: Vaccine failure was seen in 25 patients, 11 children and 14 adults, of 2594 patients diagnosed with influenza A(H1N1)v. Compared with age-matched controls, patients with vaccine failure were more often immunocompromised (Hazard Ratio, 4.89; 95% confidence interval [CI], 2.19-10.89). During the 4 weeks with maximum influenza activity, the relative risk per week for an influenza A(H1N1)v diagnosis in the vaccinated population was .06 (95% CI .008-.41), .13 (95% CI .06-.27), .05 (95% CI .02-.12), and .07 (95% CI .03-.15), respectively, corresponding to a weekly vaccine effectiveness of 87-95%. CONCLUSIONS: The monovalent AS03-adjuvanted influenza vaccine was highly effective in prevention of the pandemic influenza in Stockholm County. A single dose seemed to be sufficient in most, both children and adults, except in immunocompromised hosts.

A foodborne outbreak of Cyclospora infection in Stockholm, Sweden.

During May and June 2009 an outbreak of Cyclospora cayetanensis infection involving 12 laboratory-confirmed and 6 probable cases was detected in Stockholm County, Sweden. Imported sugar snap peas from Guatemala were the suspected vehicle, based on information obtained from patient questionnaires. This is the first reported outbreak of cyclosporiasis in Sweden and the second in Europe.

Vaccine failures after active immunisation against tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a major disease of the central nervous system in Europe and is endemic in Sweden with about 200 notified cases annually. The far most effective protective measure against TBE is active immunisation. The vaccines available today induce a high degree of protection in field studies. However, vaccine failures have occasionally been reported and may be overlooked due to different, and sometimes confusing, antibody kinetics in vaccinees with TBEV infection. In this study, 27 patients with clinical and serological evidences of TBE despite adequate immunisation are presented. Vaccination failure is characterized by a slow, and initially non-detectable, development of the specific TBEV-IgM response, seen together with a rapid rise of IgG and neutralising antibodies in serum. The majority (70%) of the patients were more than 50 years of age, which may implicate a need for a modified immunisation strategy in the elderly.

An outbreak of cryptosporidiosis associated with exposure to swimming pool water.

An outbreak of cryptosporidiosis among visitors to a public swimming pool occurred in the late summer of 2002. We performed a retrospective cohort study, including 3 cohorts, A) 178 school-children who visited the pool on a single occasion, B) 263 arbitrarily chosen school children, aged 6-12 y, and their household members, living within the municipality where the outbreak occurred, and C) an additional 28 individuals with laboratory confirmed cryptosporidiosis. The outbreak lasted 4 weeks and affected an estimated 800-1000 individuals. The primary attack rate was 40-50%. The median incubation period was 5 d (range 2-13 d). The secondary attack rate was 8-10%. Diarrhoea was reported by 93% of the patients, abdominal pain 89%, nausea 73%, and fever 40%. Fifty-four percent had<5 loose stools and 20% had>10 loose stools per d. The duration of symptoms was 4-10 d for 52% and>10 d for 34% of the cases. This is the first reported outbreak of pool associated cryptosporidiosis in Sweden and emphasizes the importance of proper control routines of swimming pools with continuous assessment of the quality of the water sources and filtration processes.