Recurrence risk of a hypotonic hyporesponsive episode in two Australian specialist immunisation clinics.

BACKGROUND: A hypotonic hyporesponsive episode (HHE) is a well-described adverse event following immunisation (AEFI) in young children. There is limited data regarding recurrence post re-vaccination. METHOD: A retrospective analysis of HHEs reported to two tertiary paediatric hospitals in Australia: The Royal Children's Hospital, Melbourne [2006-11] and the Children's Hospital Westmead, Sydney [1997-2014]. HHE definition level of confidence was allocated according to Brighton Collaboration (BC) criteria and defined immediate if within 30 min post vaccination. The Australian Immunisation Register (AIR) was utilised to document current immunisation status. RESULTS: 235 HHE cases (135 Melbourne, 100 Sydney) were identified: 47% were female and 67% (157/235) occurred following the routine dose one vaccines at 6-8 weeks of age. Median time following immunisation was 120 min (range 1 min to 14 days) An immediate HHE occurred in 43% (102/235) and by BC criteria, 74% (173/235) were level 1 (definite). Subsequent vaccines were administered under supervision in hospital in 37% overall (86/235); 43% (58/135) in Melbourne and 28% (28/100) in Sydney. HHE recurrence rate was 3% (7/235) [95% confidence interval 1-6%]. AIR records were available in 94% (221/235). At a median age of 3.1 years, 84% (186/221) were up-to-date with recommended vaccines. CONCLUSION: This study highlights the importance of specialist immunization clinics in supporting the National Immunisation Program, through follow-up and management of serious adverse events following immunization.

Fifty years of immunisation in Australia (1964-2014): the increasing opportunity to prevent diseases.

Medicine has seen dramatic changes in the last 50 years, and vaccinology is no different. Australia has made a significant contribution to world knowledge on vaccine-preventable diseases. Certain deadly diseases have disappeared or become rare in Australia following successful introduction of vaccines. As diseases become rarer, public knowledge about the diseases and their serious consequences has decreased, and concerns about potential vaccine side effects have increased. To maintain confidence in immunisations, sharing of detailed information about the vaccines and the diseases we are trying to prevent is integral to the continued success of our public health programme. Modern quality immunisation programmes need to communicate complex information to immunisation providers and also to the general community. Improving immunisation coverage rates and eliminating the gap in coverage and timeliness between Aboriginal and Torres Strait Islander peoples and non-Indigenous people has become a high priority.

Clinical epidemiology and predictors of outcome in children hospitalised with influenza A(H1N1)pdm09 in 2009: a prospective national study.

BACKGROUND: There are few large-scale, prospective studies of influenza A(H1N1)pdm09 in children that identify predictors of adverse outcomes. OBJECTIVES: We aimed to examine clinical epidemiology and predictors for adverse outcomes in children hospitalised with influenza A(H1N1)pdm09 in Australia. METHODS: Active hospital surveillance in six tertiary paediatric referral centres (June-September, 2009). All children aged <15 years admitted with laboratory-confirmed influenza A(H1N1)pdm09 were studied. RESULTS: Of 601 children admitted with laboratory-confirmed influenza, 506 (84·2%) had influenza A(H1N1)pdm09. Half (51·0%) of children with influenza A(H1N1)pdm09 were previously healthy. Hospital stay was longer in children with pre-existing condition (mean 6·9 versus 4·9 days; P = 0·02) as was paediatric intensive care unit (PICU) stay (7·0 versus 2·3 days; P = 0·005). Rapid diagnosis decreased both antibiotic use and length of hospital and PICU stay. Fifty (9·9%) children were admitted to a PICU, 30 (5·9%) required mechanical ventilation and 5 (0·9%) died. Laboratory-proven bacterial co-infection and chronic lung disease were significant independent predictors of PICU admission (OR 6·89, 95% CI 3·15-15·06 and OR 3·58, 95% CI 1·41-9·07, respectively) and requirement for ventilation (OR 5·61, 95% CI 2·2-14·28 and OR 5·18, 95% CI 1·8-14·86, respectively). Chronic neurological disease was a predictor of admission to PICU (OR 2·30, 95% CI 1·14-4·61). CONCLUSIONS: During the 2009 pandemic, influenza was a major cause of hospitalisation in tertiary paediatric hospitals. Co-infection and underlying chronic disease increased risk of PICU admission and/or ventilation. Half the children admitted were previously healthy, supporting a role for universal influenza vaccination in children.

Establishing intra- and inter-rater agreement of the Face, Legs, Activity, Cry, Consolability scale for evaluating pain in toddlers during immunization.

BACKGROUND: The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a five-item tool that was developed to assess postoperative pain in young children. The tool is frequently used as an outcome measure in studies investigating acute procedural pain in young children; however, there are limited published psychometric data in this context. OBJECTIVE: To establish inter-rater and intrarater agreement of the FLACC scale in toddlers during immunization. METHODS: Participants comprised a convenience sample of toddlers recruited from an immunization drop-in service, who were part of a larger pilot randomized controlled trial. Toddlers were video- and audiotaped during immunization procedures. The first rater scored each video twice in random order over a period of three weeks (intrarater agreement), while the second rater scored each video once and was blinded to the first rater's scores (inter-rater agreement). The FLACC scale was scored at four timepoints throughout the procedure. Intraclass correlation coefficients were used to assess agreement of the FLACC scale. RESULTS: Thirty toddlers between 12 and 18 months of age were recruited, and video data were available for 29. Intrarater agreement coefficients were 0.88 at baseline, 0.97 at insertion of first needle, and 0.80 and 0.81 at 15 s and 30 s following the final injection, respectively. Inter-rater coefficients were 0.40 at baseline, 0.95 at insertion of first needle, and 0.81 and 0.78 at 15 s and 30 s following the final injection, respectively. CONCLUSIONS: The FLACC scale has sufficient agreement in assessing pain in toddlers during immunizations, especially during the most painful periods of the procedure.

Pain management strategies used during early childhood immunisation in Victoria.

AIM: The study aims to identify pain management practices used during scheduled childhood immunisation. METHODS: A survey of members of the Australian Nurses Federation (Victorian Branch) Immunisation Nurses Special Interest Group. Questions included frequency of use of pain reduction strategies during immunisations for infants, toddlers and children, injection techniques and existence of an articulated pain management policy. RESULTS: The survey was emailed to 274 Immunisation Nurses Special Interest Group members with registered email addresses, and 125 (46%) completed the survey. Nineteen respondents (15.2%) stated their main place of employment had a pain management policy during immunisations and 20 (16.0%) respondents were not sure. Distraction strategies were frequently used during immunisation for all age groups, with 95 (76.0%) replying that distraction was used often or always. Breastfeeding during immunisation for infants younger than 6 months was used occasionally (n = 54, 44.6%), often (n = 11, 9.1%) or never (n = 55, 45.5%) and was used even less frequently for infants aged 6-12 months. Sucrose or other sweet solutions were almost never used for infants prior to, or during, immunisation. As a reward, lollies were frequently given to children after immunisations. Topical anaesthetics were almost never used in any age groups. Over half the respondents used a rapid injection technique; 55 (44.7%) used a slow technique and four respondents aspirated the needle before injections. CONCLUSIONS: Many distraction strategies were used during and following immunisation but sweet solutions, breastfeeding or topical anaesthetics were rarely used. Use of these strategies where feasible, should be facilitated in diverse settings where immunisations take place.

Changes in patterns of hospitalized children with varicella and of associated varicella genotypes after introduction of varicella vaccine in Australia.

BACKGROUND: Varicella in children, although usually mild, can cause hospitalization and rarely death. This study examined patterns of hospitalized children with varicella, and associated varicella genotypes, in 4 tertiary children's hospitals throughout Australia before and after varicella vaccine was introduced. METHODS: We obtained coded data on discharge diagnoses from each hospital before (1999 to 2001) and after (2007 to 2010) varicella vaccine introduction in 2005, adding active surveillance to capture clinical features, complications and immunization history in the latter period. Varicella vesicles were swabbed, and genotyping of varicella strains was performed by real-time polymerase chain reaction amplification. RESULTS: Overall, a 68% reduction in coded hospitalizations (varicella, 73.2% [P < 0.001]; zoster, 40% [P = 0.002]) occurred post-vaccine introduction. Of children with detailed clinical data (97 varicella and 18 zoster cases), 46 (40%) were immunocompromised. Only 6 of 32 (19%) age-eligible immunocompetent children were immunized. Complications, most commonly secondary skin infections (n = 25) and neurologic conditions (n = 14), occurred in 44% of children. There were no deaths; but 3 immunocompetent unimmunized children had severe multiple complications requiring intensive care. All strains genotyped were "wild-type" varicella, with Clade 1 (European origin) predominating. CONCLUSIONS: After the introduction of varicella vaccine, coverage of greater than 80% at 2 years of age was achieved, with varicella hospitalizations reduced by almost 70%. Of hospitalized children age-eligible for varicella vaccine, 80% were unimmunized, including all cases requiring intensive care.

Neurologic complications of influenza A(H1N1)pdm09: surveillance in 6 pediatric hospitals.

OBJECTIVE: We sought to determine the range and extent of neurologic complications due to pandemic influenza A (H1N1) 2009 infection (pH1N1'09) in children hospitalized with influenza. METHODS: Active hospital-based surveillance in 6 Australian tertiary pediatric referral centers between June 1 and September 30, 2009, for children aged <15 years with laboratory-confirmed pH1N1'09. RESULTS: A total of 506 children with pH1N1'09 were hospitalized, of whom 49 (9.7%) had neurologic complications; median age 4.8 years (range 0.5-12.6 years) compared with 3.7 years (0.01-14.9 years) in those without complications. Approximately one-half (55.1%) of the children with neurologic complications had preexisting medical conditions, and 42.8% had preexisting neurologic conditions. On presentation, only 36.7% had the triad of cough, fever, and coryza/runny nose, whereas 38.7% had only 1 or no respiratory symptoms. Seizure was the most common neurologic complication (7.5%). Others included encephalitis/encephalopathy (1.4%), confusion/disorientation (1.0%), loss of consciousness (1.0%), and paralysis/Guillain-Barré syndrome (0.4%). A total of 30.6% needed intensive care unit (ICU) admission, 24.5% required mechanical ventilation, and 2 (4.1%) died. The mean length of stay in hospital was 6.5 days (median 3 days) and mean ICU stay was 4.4 days (median 1.5 days). CONCLUSIONS: Neurologic complications are relatively common among children admitted with influenza, and can be life-threatening. The lack of specific treatment for influenza-related neurologic complications underlines the importance of early diagnosis, use of antivirals, and universal influenza vaccination in children. Clinicians should consider influenza in children with neurologic symptoms even with a paucity of respiratory symptoms.

Respiratory syncytial virus immunoprophylaxis in high-risk infants with heart disease.

AIM: Passive immunisation with palivizumab is recommended in many countries for children with haemodynamically significant cardiac disease. We trialled respiratory syncytial virus (RSV) immunoprophylaxis in such infants during 2008­2009. METHODS: We identified all RSV admissions between 2005­2009 and examined all patients with significant cardiac disease who received palivizumab in 2008­2009. RESULTS: Infants with symptomatic cardiac disease had a more complicated course of RSV bronchiolitis with longer hospital stay, more frequent intensive care admission, longer intensive care stay and were more likely to receive respiratory support (all P < 0.05). One hundred seventeen infants with symptomatic cardiac disease received palivizumab. Of these, two (1.7%) required admission for RSV bronchiolitis. Overall, there was a reduction in admission of infants with symptomatic cardiac disease with RSV bronchiolitis in 2008­2009 (2% per year) compared with 2005­2007 (5­9% per year; P < 0.03). The number of patients with symptomatic cardiac disease who required intensive care for RSV bronchiolitis in the same period was unchanged, as a number presented to our service with RSV infection prior to commencing immunoprophylaxis or having had their cardiac diagnosis made in other centres. CONCLUSIONS: Compared with other infants, those with haemodynamically significant cardiac disease have a more complicated course of illness with RSV bronchiolitis. In these infants, palivizumab reduced the number of hospitalisations because of RSV. Cohorting patients for maximal palivizumab use reduced overall cost. To significantly impact on intensive care admissions overall, immunoprophylaxis should be considered at a regional level.

Ethical issues in preventing mother-to-child transmission of hepatitis B by immunisation.

Without intervention, a pregnant woman who is a chronic hepatitis B carrier is at risk of transmitting hepatitis B and of her infant becoming a chronic carrier and having a significantly increased lifetime risk of developing liver cancer or cirrhosis. Hepatitis B vaccine and immunoglobulin reduce the risk of the baby becoming a carrier, but with only a short window period after birth to deliver this potentially life-saving intervention. We reviewed the evidence on the magnitude of the risk. If the carrier mother is e antigen positive (highly infective), the calculated risk to the infant without intervention is 75.2%, reduced to 6.0% by giving vaccine and immunoglobulin at birth. If the mother is surface antigen positive but e antigen negative, the risk to the infant without intervention is 10.3%, reduced to 1.0% by giving vaccine and immunoglobulin. If vaccine is accepted but immunoglobulin refused, as for example by some Jehovah's Witnesses, the risk to babies of e antigen positive mothers is reduced to 21.0% and to babies of e antigen negative mothers to 2.6%. These figures can be used to inform parents and as a possible basis for child protection proceedings if parents decline vaccine and/or immunoglobulin. We argue from the perspective of the best interests of the child that the severity of the condition justifies initiating child protection proceedings whenever a baby is born to a hepatitis B carrier mother and, despite concerted attempts to persuade them, the parents refuse vaccine and/or immunoglobulin.

Recurrent apnoea post immunisation: Informing re-immunisation policy.

BACKGROUND: Preterm infants should receive immunisations according to their chronological, rather than gestational, age however concern about possible adverse events following immunisation (AEFI) in this group often means routine immunisations are delayed. A small number of infants may have apnoea with or without bradycardia temporally associated with immunisation. The risk factors for, and recurrence rate of apnoea with subsequent immunisations are unknown, which makes planning for subsequent immunisations for these highly vulnerable infants difficult. AIM: To determine recurrence rates for apnoea temporally associated with immunisation in preterm and term infants and to explore potential risk factors associated with recurrent apnoea in preterm infants. METHOD: A retrospective analysis of all apnoea +/-bradycardia AEFIs in preterm and term infants, reported to the Surveillance of Adverse Events Following Vaccination In the Community (SAEFVIC), Victoria, Australia over a 3-year period from May 2007 to April 2010. Apnoea +/-bradycardia was defined as temporally associated with immunisation if it occurred up to 48h after immunisation. RESULTS: 7 out of 38 [18%, 95% confidence interval 6-31%] preterm infants with apnoea +/-bradycardia post initial immunisation had recurrent apnoea with subsequent immunisations. Possible risk factors for recurrence included: lower birth weight (p=0.04) and ongoing hospitalisation for complications relating to prematurity (p=0.01). No preterm infant with recurrent apnoea had a third episode of apnoea with subsequent immunisation. None of the 8 term infants with a reported apnoea AEFI had recurrence of apnoea with subsequent immunisation. CONCLUSION: There is a risk of recurrence of apnoea associated with immunisation in preterm infants. We recommend that preterm infants with apnoea post immunisation should receive reliable cardio-respiratory monitoring for a minimum of 24h following the next scheduled immunisation.

Recurrence of extensive injection site reactions following DTPa or dTpa vaccine in children 4-6 years old.

OBJECTIVES: The aim of this study was to compare the immunogenicity and reactogenicity of a lower dose diphtheria, tetanus and pertussis vaccine (dTpa) with the recommended vaccine (DTPa) given as a fifth dose to 4-6-year old children who previously experienced an extensive injection site reaction (ISR). MATERIAL AND METHODS: Children aged 4-6 years who had experienced an extensive ISR following a 4th dose of DTPa were recruited and randomly assigned to receive either the recommended DTPa or the lower dose dTpa vaccine. Parents recorded local reactions and systemic events for 15 days following vaccination. Immunogenicity was assessed pre and post vaccination by ELISA for diphtheria (D), tetanus (T), pertussis toxin (PT), filamentous haemagglutinin (FHA), and pertactin (PRN). RESULTS: A total of 53 participants were vaccinated. There was a 72% recurrence rate of ISR, with a trend (p=0.055) towards fewer ISR in the dTpa (61.5%) compared with the DTPa group (85.2%). There was no difference in reports of pain or irritability between groups. All participants had seroprotective levels of antibody to D and T and seroresponse to each of the 3 pertussis antigens following vaccination with higher GMCs in DTPa vs dTpa group. There was no increase in antibody avidity observed post vaccination, regardless of vaccine given. CONCLUSION: Recurrence of ISR with the 5th dose of diphtheria, tetanus and pertussis vaccination in children who have previously experienced an extensive ISR is high. Vaccination with a dTpa vaccine may reduce the risk of fifth dose ISR.

Syncope and seizures following human papillomavirus vaccination: a retrospective case series.

OBJECTIVE: To quantify and characterise the reports of syncope and seizures following quadrivalent (4v) human papillomavirus (HPV) vaccination. DESIGN AND SETTING: Retrospective case series of notifications to SAEFVIC (Surveillance of Adverse Events Following Vaccination In the Community), May 2007 - April 2009. MAIN OUTCOME MEASURES: Incidence of syncope and seizure following 4vHPV vaccination; clinical outcomes. RESULTS: 97/1653 SAEFVIC reports met the study criteria: afebrile seizures (3), syncopal seizures (31) and syncope alone (63). Median age at vaccination was 15 years (range, 8-26 years). Injuries were reported in seven cases, including one vertebral fracture. A SAEFVIC clinic review was undertaken in 41% (40/97) and 22 patients received further 4vHPV vaccine doses administered supine, with no recurrences. The reporting rate after 4vHPV vaccine for syncope and syncopal seizures was 7.8/100, 000 and 2.6/100, 000 doses distributed, respectively. CONCLUSION: Syncope and syncopal seizures occurred after 4vHPV vaccination in Victoria at rates similar to those seen internationally. Clinical review allowed clarification of the diagnosis and management, including safe administration of further doses under supervision.

Optimizing immunization in pediatric special risk groups.

This article analyzes the current recommended practices and evidence in the immunization of pediatric 'special risk groups'. Special risk group patients are at higher risk of vaccine-preventable diseases and hence require additional strategies to maximize protection against these diseases. The special risk groups include those with an underlying chronic disease, some of whom are on immunosuppressive therapy to treat that condition. The article uses four special risk groups (acute lymphoblastic leukemia; preterm birth; juvenile idiopathic arthritis; and inflammatory bowel disease), to highlight the management considerations and potential vaccination strategies. The risks, benefits and timing of vaccination in the setting of immunosuppression require detailed discussion with treating clinicians, in particular the use of live-attenuated vaccines. The immunogenicity of vaccines in these special risk groups helps provide the evidence base for their immunization guidelines. Protection can include 'cocooning' (i.e., ensuring appropriate immunizations within the immediate family; e.g., varicella, influenza and pertussis vaccination). Improving timeliness and minimizing missed opportunities to vaccinate individuals with these special risk conditions will also optimize protection from vaccine-preventable diseases.

Immunisation rates of children with cystic fibrosis using the Australian Childhood Immunisation Register.

AIM: The Australian Immunisation Handbook (ninth edition) recommends children with cystic fibrosis (CF) receive routine scheduled immunisations plus annual influenza vaccine and an additional pneumococcal vaccine at both 12 months and 4-5 years. Adherence with these recommendations is unknown. This study aimed to determine the immunisation status of children with CF attending the Royal Children's Hospital (RCH), Melbourne. METHODS: A retrospective audit of children with CF aged 6 months to 7 years (at 1 January 2008) was performed on the RCH CF outpatient clinic database. The Australian Childhood Immunisation Register (ACIR) and RCH Immunisation Service records were used to determine immunisation status. RESULTS: Eighty-nine children with CF were identified, 52 (58%) were male, with median age of 3.6 years. Eighty-two of 89 children (92%) were up to date with routine immunisations. According to the ACIR, of the 89 children sampled, 24 (27%) were given influenza vaccine in accordance with recommendations in 2007. Eighty children were older than 12 months of age at 1 January 2008 and 17 (21%) of these children had received the additional pneumococcal vaccine at 12 months. Thirty-eight children were older than 4 years of age at 1 January 2008 and 6 (16%) received the recommended 23vPPV booster. CONCLUSION: Most children with CF received their routine childhood immunisations but not the additional recommended immunisations. This highlights the potential value of the ACIR to accurately record all vaccines administered and for ACIR reminder letters to include the additional vaccines for children in special-risk groups.

Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study.

OBJECTIVE: To describe the outcomes of clinical evaluation, skin testing, and vaccine challenge in adolescent schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine introduced in Australian schools in 2007. DESIGN: Retrospective cohort study. SETTING: Two tertiary paediatric allergy centres in Victoria and South Australia, Australia. PARTICIPANTS: 35 schoolgirls aged 12 to 18.9 years with suspected hypersensitivity reactions to the quadrivalent human papillomavirus vaccine. MAIN OUTCOME MEASURES: Clinical review and skin prick and intradermal testing with the quadrivalent vaccine and subsequent challenge with the vaccine. RESULTS: 35 schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine were notified to the specialised immunisation services in 2007, after more than 380 000 doses had been administered in schools. Of these 35 schoolgirls, 25 agreed to further evaluation. Twenty three (92%) experienced reactions after the first dose. Thirteen (52%) experienced urticaria or angio-oedema, and of these, two experienced anaphylaxis. Thirteen had generalised rash, one with angio-oedema. The median time to reaction was 90 minutes. Nineteen (76%) underwent skin testing with the quadrivalent vaccine: all were skin prick test negative and one was intradermal test positive. Eighteen (72%) were subsequently challenged with the quadrivalent vaccine and three (12%) elected to receive the bivalent vaccine. Seventeen tolerated the challenge and one reported limited urticaria four hours after the vaccine had been administered. Only three of the 25 schoolgirls were found to have probable hypersensitivity to the quadrivalent vaccine. CONCLUSION: True hypersensitivity to the quadrivalent human papillomavirus vaccine in Australian schoolgirls was uncommon and most tolerated subsequent doses.

A simple intervention to improve hospital antibiotic prescribing.

OBJECTIVE: To evaluate changes in prescribing behaviour after distribution of antibiotic guidelines printed on a 9 x 6 cm laminated card suitable for clipping to a hospital identification badge. INTERVENTION: Guidelines for appropriate antibiotic prescribing for 20 common and important paediatric infections were printed on a laminated 9 x 6 cm card suitable to clip to a hospital identification badge and distributed to all medical staff. DESIGN: We collected data from medical records for three marker conditions (tonsillitis, pneumonia, and orbital/periorbital cellulitis) on samples of patients from the six-month periods either side of the month in which the cards were distributed. Prescribers were unaware of the study and investigators analysed the prescriptions without knowledge of the period in which they were written. Prescriptions were rated for appropriate choice of antibiotic and appropriate dose. Data were also collected on antibiotic costs. MAIN OUTCOME MEASURES: Proportion of cases in which antibiotic choice was appropriate; proportion of cases in which antibiotic dose was appropriate; annualised costs of third-generation cephalosporins. RESULTS: For tonsillitis there was little change in prescribing practice after the cards were introduced. For pneumonia, cases with appropriate choice increased from 77% to 92% (P = 0.028) and cases with appropriate dose increased from 48% to 81% (P = 0.001). For orbital/periorbital cellulitis, cases with appropriate choice increased from 19% to 78% (P < 0.001) and cases with appropriate dose increased from 30% to 51% (P = 0.11). Annualised costs of third-generation cephalosporins were $193 245 pre-cards and $89 814 post-cards. CONCLUSION: The cards appeared to have a beneficial effect on prescribing practice for the three marker conditions. This simple intervention is likely to be cost-effective and useful in reducing inappropriate use of antibiotics.