Influenza epidemiology, vaccine coverage and vaccine effectiveness in children admitted to sentinel Australian hospitals in 2014: The influenza complications alert network (FluCAN)

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance programme operating in all states and territories in Australia. We summarise the epidemiology of children hospitalised with laboratory-confirmed influenza in 2014 and reports on the effectiveness of inactivated trivalent inactivated vaccine (TIV) in children. In this observational study, cases were defined as children admitted with acute respiratory illness (ARI) with influenza confirmed by PCR. Controls were hospitalised children with ARI testing negative for influenza. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio of vaccination in influenza positive cases compared with test-negative controls using conditional logistic regression models. From April until October 2014, 402 children were admitted with PCR-confirmed influenza. Of these, 28% were aged < 1 year, 16% were Indigenous, and 39% had underlying conditions predisposing to severe influenza. Influenza A was detected in 90% of cases of influenza; influenza A(H1N1)pdm09 was the most frequent subtype (109/141 of subtyped cases) followed by A(H3N2) (32/141). Only 15% of children with influenza received antiviral therapy. The adjusted VE of one or more doses of TIV for preventing hospitalised influenza was estimated at 55.5% (95% confidence intervals (CI): 11.6–77.6%). Effectiveness against influenza A(H1N1)pdm09 was high (91.6%, 95% CI: 36.0–98.9%) yet appeared poor against H3N2. In summary, the 2014 southern hemisphere TIV was moderately effective against severe influenza in children. Significant VE was observed against influenza A(H1N1)pdm0

Epidemiological characteristics of varicella from 2000 to 2008 and the impact of nationwide immunization in Taiwan

[[abstract]]Background: Varicella has an important impact on public health. Starting in 2004 in Taiwan, nationwide free varicella vaccinations were given to 1-year-old children.Methods: Our study investigated the epidemiological characteristics of varicella from 2000 to 2008, and assessed the change of varicella epidemiology after the mass varicella immunization. ICD-9-CM codes related to varicella or chickenpox (052, 052.1, 052.2, 052.7, 052.8, 052.9) were analyzed for all young people under 20 years of age through the National Health Insurance database of Taiwan from 2000 to 2008.Results: Case numbers of varicella or chickenpox significantly declined after the nationwide immunization in 2004. Winter, particularly January, was the epidemic season of varicella. We found a significant post-vaccination decrease in incidence among preschool children, especially 3 to 6 year-old children-- the peak incidence was 66 per thousand for 4 and 5 year-old children before the nationwide immunization (2000 to 2003), and the peak incidence was 23 per thousand for 6 year-old children in 2008 (p < 0.001). Varicella-related hospitalization also significantly decreased in children younger than 6 years after the nationwide immunization.Conclusion: The varicella annual incidence and varicella-related hospitalization markedly declined in preschool children after nationwide varicella immunization in 2004

Paediatric Active Enhanced Disease Surveillance (PAEDS) 2017 and 2018: Prospective hospital-based surveillance for serious paediatric conditions

Introduction: The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is a hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine-preventable diseases and potential adverse events following immunisation (AEFI). This report presents surveillance data for 2017 and 2018. Methods: Specialist nurses screened hospital admissions, emergency department (ED) records, laboratory and other data on a daily basis in seven paediatric tertiary referral hospitals across Australia to identify children with the conditions under surveillance. In 2017 and 2018 these included acute flaccid paralysis (AFP; a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis, varicella-zoster virus infection (varicella and herpes zoster), invasive meningococcal, and invasive Group A streptococcus diseases. An additional social research component was added to evaluate parental attitudes to vaccination. Results: PAEDS captured 1,580 and 925 cases for 2017 and 2018, respectively, across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach the World Health Organization reporting targets; identification of a third human parechovirus outbreak among other infectious diseases linked to ACE; demonstration of variable influenza activity between 2017 and 2018, with vaccine effectiveness (VE) analysis demonstrating that the protection offered through vaccination is season-dependent. All IS cases associated with vaccine receipt were reported to the relevant state health department. Varicella and herpes zoster case numbers remained unchanged, with vaccine uptake found to be suboptimal among eligible children under the NIP. Enhanced pertussis surveillance continues to capture controls for VE estimation. Surveillance for invasive meningococcal disease showed predominance for serotype B at 57% over 2 years among 77 cases where serotyping was available, and surveillance for invasive group A streptococcus captured severe disease in children. Conclusion: PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using hospital-based sentinel surveillance

Australian rubella serosurvey 2012–2013: On track for elimination?

Background: The World Health Organization has targeted rubella virus for elimination regionally. Australia was one of the first countries to implement a nationally funded rubella immunisation program, in 1971, and conducts regular national rubella serosurveillance studies. We aimed to estimate the seroprevalence of rubella-specific IgG antibody in the Australian population by age and sex in 2012–2013, to compare the results with three previous serosurveys conducted in 1996–1999, 2002 and 2007 and to estimate the effective reproduction numbers (Rn). Methods: This study used 2729 serum and plasma specimens, randomly selected from a specimen bank collected in 2012–2013 across Australia. Age groups included in the sample ranged from 1 to 49 years. Sera were tested for rubella-specific IgG-antibody using the Enzygnost anti-rubella IgG enzyme immunoassay and classified as positive, negative or equivocal according to rubella-specific IgG concentrations of >7 IU/ml, <3 IU/ml and 3–7 IU/ml, respectively. Results: The overall proportions seropositive, seronegative and equivocal for rubella-specific IgG were 92.1% (95% CI, 91.0–93.2), 6.7% (95% CI, 5.7–7.7) and 1.2% (95% CI, 0.8–1.6), respectively. The proportion of males seropositive was significantly lower than females in the 30–34 (83.1% vs. 96.8%, p = 0.003), 35–39 (86.1% vs. 96.3%, p = 0.02) and 40–44 (86.1% vs. 95.7%, p = 0.03) year age groups. Rn for rubella in 2012–2013 was estimated to be 0.33 (95% CI 0.28–0.39). Discussion: The 2012–2013 national serosurvey showed levels of rubella-specific IgG seropositivity in the Australian population are relatively high with no evidence of decrease compared to previous serosurveys conducted in 1996–1999, 2002 and 2007. The lower proportion of seropositive males aged 30–44 years likely reflects the initial immunisation program targeting females only. To our knowledge this study represents the longest period of serosurveillance following introduction of a nationally funded rubella immunisation program. The lack of evidence of decreasing rubella-specific IgG seropositivity is therefore reassuring for Australia and other countries with longstanding high vaccine coverage

SCN1A

OBJECTIVE: Febrile seizures may follow vaccination. Common variants in the sodium channel gene, SCN1A, are associated with febrile seizures, and rare pathogenic variants in SCN1A cause the severe developmental and epileptic encephalopathy Dravet syndrome. Following vaccination, febrile seizures may raise the specter of poor outcome and inappropriately implicate vaccination as the cause. We aimed to determine the prevalence of SCN1A variants in children having their first febrile seizure either proximal to vaccination or unrelated to vaccination compared to controls. METHODS: We performed SCN1A sequencing, blind to clinical category, in a prospective cohort of children presenting with their first febrile seizure as vaccine proximate (n = 69) or as non-vaccine proximate (n = 75), and children with no history of seizures (n = 90) recruited in Australian pediatric hospitals. RESULTS: We detected 2 pathogenic variants in vaccine-proximate cases (p.R568X and p.W932R), both of whom developed Dravet syndrome, and 1 in a non-vaccine-proximate case (p.V947L) who had febrile seizures plus from 9 months. All had generalized tonic-clonic seizures lasting >15 minutes. We also found enrichment of a reported risk allele, rs6432860-T, in children with febrile seizures compared to controls (odds ratio = 1.91, 95% confidence interval = 1.31-2.81). INTERPRETATION: Pathogenic SCN1A variants may be identified in infants with vaccine-proximate febrile seizures. As early diagnosis of Dravet syndrome is essential for optimal management and outcome, SCN1A sequencing in infants with prolonged febrile seizures, proximate to vaccination, should become routine. ANN NEUROL 2020;87:281-288

Febrile seizures following measles and varicella vaccines in young children in Australia

BACKGROUND: Febrile seizures (FS) are common in childhood with incidence peaking in the second year of life when measles and varicella-containing vaccines are administered. This study aimed to examine the vaccine-attributable risk of FS following separate administration of MMR and monovalent varicella vaccines (VV) prior to a planned change to MMRV as the second dose of measles-containing vaccine at 18 months of age. METHODS: All FS cases in children aged <5 years from 1st January 2012 to 30th April 2013 were identified from emergency department (ED) and inpatient databases at five Australian tertiary paediatric hospitals participating in PAEDS (Paediatric Active Enhanced Disease Surveillance). Immunization records were obtained from the Australian Childhood Immunization Register (ACIR). The relative incidence (RI) of FS following MMR dose 1 (MMR1) and VV in children aged 11-23 months was determined using the self-controlled case series (SCCS) method and used to calculate attributable risk. RESULTS: There were 2013 FS episodes in 1761 children. The peak age at FS was 18 months. The risk of FS was significantly increased 5-12 days post receipt of MMR1 at 12 months (RI=1.9 [95% CI: 1.3-2.9]), but not after VV at 18 months (RI=0.6 [95% CI: 0.3-1.2]. The estimated excess annual number of FS post MMR1 was 24 per 100,000 vaccinated children aged 11-23 months (95% CI=7-49 cases per 100,000) or 1 per 4167 doses. CONCLUSIONS: Our study detected the expected increased FS risk post MMR1 vaccine at 12 months, but monovalent varicella vaccine at age 18 months was not associated with increased risk of FS. This provides baseline data to assess the risk of FS post MMRV, introduced in Australia as the second dose of measles-containing vaccine at 18 months of age in July 2013

Primary culture of intestinal epithelial cells as a potential model for Toxoplasma gondii enteric cycle studies

The primary culture of intestinal epithelial cells from domestic cats is an efficient cellular model to study the enteric cycle of Toxoplasma gondii in a definitive host. The parasite-host cell ratio can be pointed out as a decisive factor that determines the intracellular fate of bradyzoites forms. The development of the syncytial-like forms of T. gondii was observed using the 1:20 bradyzoite-host cell ratio, resulting in similar forms described in in vivo systems. This alternative study potentially opens up the field for investigation into the molecular aspects of this interaction. This can contribute to the development of new strategies for intervention of a main route by which toxoplasmosis spreads