Tom Snelling

Case-Control Evaluation of the Effectiveness of the G1P[8] Human Rotavirus Vaccine during an Outbreak of Rotavirus G2P[4] Infection in Central Australia

UNLABELLED The human rotavirus vaccine was evaluated during an outbreak of rotavirus G2P[4] infection in central Australia. No overall protective effect against hospitalization was demonstrated, raising concerns over the durability of vaccine protection against heterotypic strains. BACKGROUND Two and a half years after commencing routine vaccination with human rotavirus vaccine, an outbreak of rotavirus G2P[4] infection occurred in central Australia. Vaccine effectiveness against a P[8]-containing strain (G9P[8]) had been demonstrated previously in this setting. This subsequent outbreak provided the opportunity to evaluate vaccine effectiveness against hospitalizations for a non-vaccine-related genotype in the same population. METHODS A case-control study was nested within a cohort of vaccine-eligible children listed on a population-based immunization register. Children with rotavirus-confirmed gastroenteritis were individually matched by date of birth and Indigenous status with 4 control subjects. RESULTS Forty-one cases met the inclusion criteria, and 21 were severe cases among infants aged <12 months. Nineteen (46%) of 41 case patients had received 2 doses of human rotavirus vaccine, compared with 87 (53%) of 164 control subjects. Vaccine effectiveness against rotavirus-related hospitalization was 19% (odds ratio, .81; 95% confidence interval, .32-2.05) for 2 doses compared with none. On secondary analysis, there was evidence of a protective effect against disease complicated by acidosis in the subset of infants aged <12 months (odds ratio, .15; 95% confidence interval, .03-.84). CONCLUSIONS Evidence was not found for an overall protective effect of human rotavirus vaccine against hospitalization for rotavirus disease in this setting. Post hoc analyses suggested a protective effect against severe disease in young infants.

Rotavirus and the indigenous children of the Australian outback: monovalent vaccine effective in a high-burden setting

Indigenous children living in arid Central Australia experience frequent outbreaks of rotavirus gastroenteritis. A widespread outbreak of G9 rotavirus infection occurred several months after introduction of the RIX4414 rotavirus vaccine. We performed a retrospective case-control study to determine vaccine efficacy during the outbreak. Two doses provided an estimated vaccine efficacy of 77.7% (95% confidence interval, 40.2%-91.7%) against hospitalization for gastroenteritis. Vaccine efficacy was 84.5% (95% confidence interval, 23.4%-96.9%) against confirmed cases of rotavirus infection. Vaccination was effective in this high-burden setting.

Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective

Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups.

Waning vaccine immunity in teenagers primed with whole cell and acellular pertussis vaccine: recent epidemiology

The recent epidemics of pertussis (whooping cough) in parts of the USA and Australia have led to the largest numbers of annual cases reported in over half a century. These epidemics demonstrated a new pattern, with particularly high rates of disease among pre-adolescents and early adolescents. These high rates of pertussis coincided with the first cohorts vaccinated with purely acellular pertussis vaccine, which replaced whole-cell pertussis (wP) vaccine in the later 1990s in the USA and Australia. Studies undertaken during these epidemics provide new evidence of more rapid waning of acellular pertussis-containing vaccines and longer-term protection from effective wP-containing vaccines. There is evidence that receiving wP as at least the first dose of pertussis-containing vaccine provides greater and more long-lived protection, irrespective of the nature of subsequent doses. This evidence will be reviewed together with the immunobiology associated with both vaccines, and the implications for pertussis control discussed.

Parental Tdap Boosters and Infant Pertussis: A Case-Control Study

BACKGROUND: Although recommended for almost a decade, evidence for field effectiveness of vaccinating close adult contacts of newborn infants against pertussis (“cocooning”) is lacking. We evaluated the impact of a government-funded cocoon program during a pertussis epidemic in New South Wales, Australia. METHODS: We matched all New South Wales laboratory-confirmed pertussis cases aged <4 months with onset between April 1, 2009, to March 30, 2011 to controls from the state birth register by date of birth and area of residence. Parental vaccine receipt was by self-report, with a subset verified. Parents were considered “immunized” if vaccinated ≥4 weeks before case symptom onset. The effectiveness of parental immunization (versus neither vaccinated) was quantified as (1 – odds ratio) × 100%. RESULTS: Case households had fewer immunized mothers (22% vs 32%) or fathers (20% vs 31%) but were more likely to include additional and older children. After adjustment, when both parents met our definition of immunized, risk of pertussis at<4 months of age was reduced by 51% (95% confidence interval 10% to 73%). Maternal vaccination prepregnancy and an immunized father reduced the risk by 51% (95% confidence interval 0% to 76%). CONCLUSIONS: Timely parental pertussis boosters provided significant protection. Evidence of protection from maternal vaccination prepregnancy is biologically plausible, and more precise data on the magnitude and duration of this is important for future policy recommendations.

Duration of Protection After First Dose of Acellular Pertussis Vaccine in Infants

OBJECTIVE: Data on the effectiveness of the diphtheria–tetanus–acellular pertussis (DTaP) vaccine in the first 4 years of life are sparse. We evaluated the vaccine effectiveness (VE) of 1 and 2 doses of DTaP before 6 months of age and of 3 doses from 6 months of age in Australia, where, since 2003, a fourth dose is not given until 4 years. METHODS: We matched reported pertussis cases aged 2 to 47 months between January 2005 and December 2009 to controls from a population-based immunization register by date of birth and region of residence. VE by number of doses and age group was calculated as (1 – odds ratio) × 100%. RESULTS: VE against hospitalization increased from 55.3% (95% confidence interval [CI], 42.7%–65.1%) for 1 dose before 4 months of age to 83.0% (95% CI, 70.2%–90.3%) for 2 doses before 6 months. The VE of 3 doses of DTaP against all reported pertussis was 83.5% (95% CI, 79.1%–87.8%) between 6 and 11 months, declining to 70.7% (95% CI, 64.5%–75.8%) between 2 and 3 years of age and 59.2% (95% CI, 51.0%–66.0%) between 3 and 4 years of age. CONCLUSIONS: DTaP provided good protection against pertussis in the first year of life from the first dose. Without a booster dose, the effectiveness of 3 doses waned more rapidly from 2 to 4 years of age than previously documented for children >6 years of age who had received 5 doses.

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.

Geographic variation in the eukaryotic virome of human diarrhea

Abstract Little is known about the population of eukaryotic viruses in the human gut (“virome”) or the potential role it may play in disease. We used a metagenomic approach to define and compare the eukaryotic viromes in pediatric diarrhea cohorts from two locations (Melbourne and Northern Territory, Australia). We detected viruses known to cause diarrhea, non-pathogenic enteric viruses, viruses not associated with an enteric reservoir, viruses of plants, and novel viruses. Viromes from Northern Territory children contained more viral families per sample than viromes from Melbourne, which could be attributed largely to an increased number of sequences from the families Adenoviridae and Picornaviridae (genus enterovirus). qRT-PCR/PCR confirmed the increased prevalence of adenoviruses and enteroviruses. Testing of additional diarrhea cohorts by qRT-PCR/PCR demonstrated statistically different prevalences in different geographic sites. These findings raise the question of whether the virome plays a role in enteric diseases and conditions that vary with geography.

Management of invasive group A streptococcal infections.

Invasive group A streptococcal (GAS) disease in children includes deep soft tissue infection, bacteraemia, bacteraemic pneumonia, meningitis and osteomyelitis. The expression of toxins and super antigens by GAS can complicate infection by triggering an overwhelming systemic inflammatory response, referred to as streptococcal toxic shock syndrome (STSS). The onset and progression of GAS disease can be rapid, and the associated mortality high. Prompt antibiotics therapy and early surgical debridement of infected tissue are essential. Adjunctive therapy with intravenous immunoglobulin and hyperbaric therapy may improve outcomes in severe disease. Nosocomial outbreaks and secondary cases in close personal contacts are not uncommon; infection control measures and consideration of prophylactic antibiotics to those at high risk are important aspects of disease control. To reduce a substantial part of the global burden of GAS disease, an affordable GAS vaccine with efficacy against a broad number of strains is needed.

Prevalence and determinants of influenza vaccine coverage at tertiary pediatric hospitals

Despite long-standing recommendations, the uptake of influenza vaccination in children with high risk medical conditions is low. This study aimed to examine the uptake of influenza vaccination amongst a cohort of Australian children and factors associated with vaccine acceptance. Three hundred and sixteen parents of children attending outpatient clinics at the two pediatric hospitals in Sydney were recruited. The reported vaccination coverage rate was 41% among children with high risk conditions and 14% among standard risk children. There was a median of three clinic visits per high risk child at which an opportunity to vaccinate was apparently missed. Healthcare worker recommendation, having a high risk condition and parental beliefs about influenza and influenza vaccination were the most important determinants of vaccine uptake. Further studies on the beliefs and practices of doctors in this area will help guide interventions to improve vaccination rates in high risk children.