Parveen Fathima

Systematic review and meta-analysis of respiratory viral coinfections in children

Respiratory infections are a common cause of paediatric morbidity. Clinical outcomes in children hospitalized with single respiratory virus infection are compared with those with two or more viral–viral coinfection. Studies were restricted to those reporting on children aged less than 5 years (PROSPERO CRD#42014009133). Published data to calculate risk ratios (RR) comparing children with single viral infections to coinfection using a random effects model were used. Similar analyses by pathogen pairs and by excluding children with comorbidities were performed. Of 4443 articles reviewed, 19 were included. Overall, no differences in the risk of fever, admission to an intensive care unit (ICU), oxygen use, mechanical ventilation and abnormal radiographs between children with single infection and those with coinfection were found. When analysing only children without comorbidities, the risk of fever (RR = 1.16 to RR = 1.24, 95% confidence intervals (CI) = 1.00–1.55) and ICU admission (RR = 1.08 to RR = 1.31, 95% CI = 0.93–1.83) increased but remained non‐significant. Point estimates suggested an increased risk of ICU admission in those coinfected with either respiratory syncytial virus or human metapneumovirus compared with those with single infection but was non‐significant. Our findings suggest that coinfection is not associated with increased clinical severity, but further investigations by pathogen pairs are warranted.

Time series analysis of RSV and bronchiolitis seasonality in temperate and tropical Western Australia

Respiratory syncytial virus (RSV) causes respiratory illness in young children and is most commonly associated with bronchiolitis. RSV typically occurs as annual or biennial winter epidemics in temperate regions, with less pronounced seasonality in the tropics. We sought to characterise and compare the seasonality of RSV and bronchiolitis in temperate and tropical Western Australia. We examined over 13 years of RSV laboratory identifications and bronchiolitis hospitalisations in children, using an extensive linked dataset from Western Australia. We applied mathematical time series analyses to identify the dominant seasonal cycle, and changes in epidemic size and timing over this period. Both the RSV and bronchiolitis data showed clear winter epidemic peaks in July or August in the southern Western Australia regions, but less identifiable seasonality in the northern regions. Use of complex demodulation proved very effective at comparing disease epidemics. The timing of RSV and bronchiolitis epidemics coincided well, but the size of the epidemics differed, with more consistent peak sizes for bronchiolitis than for RSV. Our results show that bronchiolitis hospitalisations are a reasonable proxy for the timing of RSV detections, but may not fully capture the magnitude of RSV epidemics.

The Impact of Pneumococcal Vaccination on Bacterial and Viral Pneumonia in Western Australian Children: Record Linkage Cohort Study of 469589 Births, 1996–2012

Background Pneumococcal conjugate vaccine (PCV) was included in Australias National Immunisation Program for all children from 2005. We assessed the impact of PCV on all-cause and pathogen-specific pneumonia hospitalizations in Western Australian (WA) children aged ≤16 years. Methods All hospitalizations with pneumonia-related International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification diagnosis codes occurring in WA-born children (1996-2012) were linked to pathology records. Age-specific incidence rate ratios and temporal trends for all-cause and pathogen-specific pneumonia hospitalizations were calculated before and after PCV introduction. Results Among 469589 births, there were 15175 pneumonia-related hospitalizations. Hospitalization rates were 6.7 (95% confidence interval, 6.4-6.9) times higher in Aboriginal than in non-Aboriginal children. Following PCV introduction, all-cause pneumonia hospitalizations showed significant declines across all age groups. A pathogen was identified in 2785 of 6693 (41.6%) pneumonia hospitalizations that linked to a pathology record. Respiratory syncytial virus (RSV) was most frequently identified, with RSV-associated pneumonia hospitalization rates of 89.6/100000 child-years in Aboriginal and 26.6/100000 child-years in non-Aboriginal children. The most common bacterial pathogen was Streptococcus pneumoniae in Aboriginal children (32.9/100000 child-years) and Mycoplasma pneumoniae in non-Aboriginal children (8.4/100000 child-years). Viral pneumonia rates declined in all children following PCV introduction, with the greatest declines seen in non-Aboriginal children; declines in bacterial pneumonia were observed in non-Aboriginal children. Conclusions Based on our ecological analyses, PCV seems to have had an impact on hospitalizations for pneumonia, suggesting that the pneumococcus is likely to play a role in both bacterial and viral pneumonia. Respiratory viruses remain an important pathogen in childhood pneumonia. Vaccines targeting respiratory viruses are needed to combat the residual burden of childhood pneumonia.

Potential impact of a maternal vaccine for RSV: A mathematical modelling study

Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity and one of the main causes of hospitalisation in young children. While there is currently no licensed vaccine for RSV, a vaccine candidate for pregnant women is undergoing phase 3 trials. We developed a compartmental age-structured model for RSV transmission, validated using linked laboratory-confirmed RSV hospitalisation records for metropolitan Western Australia. We adapted the model to incorporate a maternal RSV vaccine, and estimated the expected reduction in RSV hospitalisations arising from such a program. The introduction of a vaccine was estimated to reduce RSV hospitalisations in Western Australia by 6-37% for 0-2month old children, and 30-46% for 3-5month old children, for a range of vaccine effectiveness levels. Our model shows that, provided a vaccine is demonstrated to extend protection against RSV disease beyond the first three months of life, a policy using a maternal RSV vaccine could be effective in reducing RSV hospitalisations in children up to six months of age, meeting the objective of a maternal vaccine in delaying an infants first RSV infection to an age at which severe disease is less likely.

Hospital admissions for skin infections among Western Australian children and adolescents from 1996 to 2012

The objective of this study was to describe the occurrence of skin infection associated hospitalizations in children born in Western Australia (WA). We conducted a retrospective cohort study of all children born in WA between 1996 and 2012 (n = 469,589). Of these, 31,348 (6.7%) were Aboriginal and 240,237 (51.2%) were boys. We report the annual age-specific hospital admission rates by geographical location and diagnostic category. We applied log-linear regression modelling to analyse changes in temporal trends of hospitalizations. Hospitalization rates for skin infections in Aboriginal children (31.7/1000 child-years; 95% confidence interval [CI] 31.0–32.4) were 15.0 times higher (95% CI 14.5–15.5; P<0.001) than those of non-Aboriginal children (2.1/1000 child-years; 95% CI 2.0–2.1). Most admissions in Aboriginal children were due to abscess, cellulitis and scabies (84.3%), while impetigo and pyoderma were the predominant causes in non-Aboriginal children (97.7%). Admissions declined with age, with the highest rates for all skin infections observed in infants. Admissions increased with remoteness. Multiple admissions were more common in Aboriginal children. Excess admissions in Aboriginal children were observed during the wet season in the Kimberley and during summer in metropolitan areas. Our study findings show that skin infections are a significant cause of severe disease, requiring hospitalization in Western Australian children, with Aboriginal children at a particularly high risk. Improved community-level prevention of skin infections and the provision of effective primary care are crucial in reducing the burden of skin infection associated hospitalizations. The contribution of sociodemographic and environmental risk factors warrant further investigation.

Assessment of on-time vaccination coverage in population subgroups: A record linkage cohort study

Reported infant vaccination coverage at age 12 months in Australia is >90%. On-time coverage of the 2-4-6 month schedule and coverage in specific populations is rarely reported. We conducted a population-based cohort study of 1.9 million Australian births, 1996-2012, combining individual birth and perinatal records with immunisation records through probabilistic linkage. We assessed on-time coverage across 13 demographic and perinatal characteristics of diphtheria-tetanus-pertussis vaccines (DTP) defined as vaccination 14 days prior to the scheduled due date, to 30 days afterwards. On-time DTP vaccination coverage in non-Aboriginal infants was 88.1% for the 2-month dose, 82.0% for 4-month dose, and 76.7% for 6-month dose; 3-dose coverage was 91.3% when assessed at 12 months. On-time DTP coverage for Aboriginal infants was 77.0%, 66.5%, and 61.0% for the 2-4-6 month dose; 3-dose coverage at 12 months was 79.3%. Appreciable differences in on-time coverage were observed across population subgroups. On-time coverage in non-Aboriginal infants born to mothers with ≥3 previous pregnancies was 62.5% for the 6-month dose (47.9% for Aboriginal infants); up to 23.5 percentage points lower than for first-borns. Infants born to mothers who smoked during pregnancy had coverage 8.7-10.3 percentage points lower than infants born to non-smoking mothers for the 4- and 6-month dose. A linear relationship was apparent between increasing socio-economic disadvantage and decreasing on-time coverage. On-time coverage of the 2-4-6 month schedule is only 50-60% across specific population subgroups representing a significant avoidable public health risk. Aboriginal infants, multiparous mothers, and those who are socio-economically disadvantaged are key groups most likely to benefit from targeted programs addressing vaccine timeliness.

Effectiveness of a 3 + 0 pneumococcal conjugate vaccine schedule against invasive pneumococcal disease among a birth cohort of 1.4 million children in Australia

BACKGROUND Most studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australias national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births. METHODS Births records for 2001-2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 - adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children. RESULTS Following introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9-98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5-94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4-90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children. CONCLUSION Our population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.

Active surveillance of 2017 seasonal influenza vaccine safety: an observational cohort study of individuals aged 6 months and older in Australia

Objective To actively solicit adverse events experienced in the days following immunisation with quadrivalent inactivated influenza vaccine using Australia’s near real-time, participant-based vaccine safety surveillance system, AusVaxSafety. Design and setting Observational cohort study conducted in 194 sentinel surveillance immunisation sites (primary care, hospital and community-based clinics) across Australia. Participants Individuals aged ≥6 months who received a routine seasonal influenza vaccine at a participating site (n=102 911) and responded to a survey (via short message service or email) sent 3 days after vaccination about adverse events experienced (n=73 892; 71.8%). Main outcome measure Near real-time and cumulative participant-reported rates of any adverse event, fever or medical attendance experienced within 3 days after vaccination overall, by brand, age, pregnancy status and concomitant vaccine receipt. Results Participant median age was 57 years (range: 6 months to 102 years); 58.1% (n=42 869) were female and 2.7% (n=2018) were pregnant. Near real-time fast initial response cumulative summation and Bayesian analyses of weekly event rates did not demonstrate a safety signal. Children aged 6 months to 4 years had higher event rates (522/6180; 8.4%) compared with older ages; participants aged ≥65 years reported fewer events (1695/28 154; 6.0%). There were no clinically significant differences in safety between brands, by age group or overall. Cumulative data analysis demonstrated that concomitant vaccination was associated with increased rates of fever (2.1% vs 0.8%) and medical attendance (0.8% vs 0.4%), although all rates were low and did not exceed expected levels. Conclusions Novel, postmarketing AusVaxSafety surveillance demonstrated comparable and expected safety outcomes for the 2017 quadrivalent inactivated influenza vaccine brands used in Australia. These near real-time, participant-reported data are expected to encourage confidence in vaccine safety and promote uptake.

Record linkage study of the pathogen‐specific burden of respiratory viruses in children

Reliance on hospital discharge diagnosis codes alone will likely underestimate the burden of respiratory viruses.