Microbiology of septic arthritis in young Auckland children.

BACKGROUND: Kingella kingae is an important cause of septic arthritis in young children, with modern laboratory methods leading to increased detection. Prevalence of this pathogen in New Zealand, where there are high rates of childhood infections due to Staphylococcus aureus and Streptococcus pyogenes, is not known. METHODS: We conducted a retrospective review of children <5 years with septic arthritis (without osteomyelitis) at a tertiary children's hospital in Auckland, over 10 years (2005-2014). Data were collected on demographics, microbiology, clinical presentation, investigations and management. RESULTS: Of the 68 cases of septic arthritis, 57 (83.8%) occurred in children aged <24 months. Among those <3 months, Streptococcus agalactiae (Group B streptococcus) was predominant (45.5% of 11 cases), followed by S. aureus (36.4%). The most common pathogen in those 3 to <12 months was Streptococcus pneumoniae (38.5% of 13 cases). In children aged 12 to <24 months, K. kingae was most common (30.3% of 33 cases). Of the 12 cases of K. kingae, 91.7% were identified from synovial fluid culture. All K. kingae isolates were susceptible to amoxicillin. CONCLUSIONS: K. kingae is the leading pathogen in septic arthritis in New Zealand children aged 12 to <24 months. Routine inoculation of synovial fluid into blood culture bottles at time of sample collection, in addition to use of polymerase chain reaction methods, should be encouraged to improve detection rates. For infants and preschool children presenting with single joint septic arthritis, empiric antibiotics should include cover for S. aureus and K. kingae.

Community-acquired invasive Staphylococcus aureus: Uncovering disparities and the burden of disease in Auckland children.

AIM: Staphylococcus aureus (SA) causes serious invasive disease in children. Large studies have measured the incidence of SA bacteraemia, but there is less information on the total burden of community-acquired invasive SA (iSA) in children. METHODS: A retrospective, cross-sectional analysis of Auckland resident children aged 0-14 years who were hospitalised with iSA between 2011 and 2015 was performed. Laboratory databases and SA-related international classification of diseases 10 discharge codes were searched to identify community-onset cases with SA isolated from a normally sterile site. Clinical records and coroner's reports were reviewed to determine clinical syndromes and exclude nosocomial infections. RESULTS: A total of 295 children with iSA were identified. The average annual incidence of iSA was 18.6 per 100 000 - for Pacific populations 44.3 per 100 000, Maori 24.3 per 100 000 and New Zealand European and other 8.8 per 100 000; 68% had bacteraemia. The incidence of iSA for Pacific infants was 10 times greater than non-Maori/non-Pacific (113.4/100 000 population vs. 11.8/100 000). Multivariate analysis found a higher risk of admission in Pacific children, males and those living in areas of high deprivation. Thirty-two patients (10.8%) were admitted to the intensive care unit; risk was higher in infants, Pacific children and those with respiratory infection (Relative Risk (RR) 12.2, 95% confidence interval (CI) 5.7-26.4) and multifocal (RR 6.9, 95% CI 3.4-13.8) and endovascular disease (RR 8.9, 95% CI 3.9-20.6). All deaths (n = 7) had respiratory infections, and four were patients <1 year of age. CONCLUSIONS: Studies investigating SA bacteraemia alone significantly underestimate the total burden of iSA disease. There are marked ethnic and socio-economic disparities in iSA disease among Auckland children. Pacific infants are at the highest risk.

Post-streptococcal glomerulonephritis: Some reduction in a disease of disparities.

AIM: A retrospective Auckland-wide (total population approximately 1.4 million) study of hospital admissions from 2007 to 2015 was conducted to assess trends in admissions for acute post-streptococcal glomerulonephritis (APSGN) in children aged 0-14 years. METHODS: International Statistical Classification of Diseases (ICD10) discharge codes were used to identify potential cases of APSGN, and electronic clinical records and laboratory data were compared with established case definitions for definite or probable APSGN. RESULTS: A total of 430 cases of APSGN were identified (definite n = 337, probable n = 93), with a mean annual incidence of 15.2/100 000 (95% confidence interval (CI) 14.9-15.6). Incidence (0-14 years) was 17 times higher in Pacific peoples (50.2/100 000, 95% CI 48.6-51.8) and almost 7 times higher in Maori (19.6/100 000, 95% CI 18.6-20.7) than European/other populations (2.9/100 000, 95% CI 2.7-3.1). Multivariate analysis found ethnicity, deprivation, male gender, age (peak 3-8 years) and season (summer/autumn) to be associated with admission risk. Admission rates showed a significant change of -9.0% (95% CI -10.4, 7.4%) per year, with 2011 being an exception. Low C3 complement, hypertension, elevated streptococcal titres, oedema and heavy proteinuria were present in 94, 65, 67, 52 and 49% of cases, respectively. Relying on ICD10 codes without further review of clinical notes would result in an overcount of cases by 25%. CONCLUSIONS: There is severe disparity in APSGN admission rates, with a disproportionate burden of disease for Pacific and Maori children and those living in deprived circumstances. Rates trended downward from 2007 to 2015.

Respiratory virus detection during hospitalisation for lower respiratory tract infection in children under 2 years in South Auckland, New Zealand.

AIM: To describe respiratory virus detection in children under 2 years of age in a population admitted with lower respiratory infection and to assess correlation with measures of severity. METHODS: Nasopharyngeal aspirates from infants admitted with lower respiratory tract infection (n = 1645) over a 3-year time period were tested by polymerase chain reaction. We collected epidemiological and clinical data on all children. We assessed the correlation of presence of virus with length of hospital stay, intensive care admission and consolidation on chest X-ray. RESULTS: Of the children admitted 34% were Maori, 43% Pacific and 75% lived in areas in the bottom quintile for socio-economic deprivation. A virus was found in 94% of those tested including 30% with multiple viruses. Picornavirus was present in 59% including 34% as the sole virus. Respiratory syncytial virus was found in 39%. Virus co-detection was not associated with length of stay, chest X-ray changes or intensive care unit admission. CONCLUSION: In this disadvantaged predominately Maori and Pacific population, picornavirus is commonly found as a sole virus, respiratory syncytial virus is frequent but immunisation preventable influenza is infrequent. We did not find that co-detection of viruses was linked to severity.

Comparison of illumigene Group A Streptococcus Assay with Culture of Throat Swabs from Children with Sore Throats in the New Zealand School-Based Rheumatic Fever Prevention Program.

Group A streptococcal (GAS) pharyngitis is a particularly important condition in areas of New Zealand where the incidence of acute rheumatic fever remains unacceptably high. Prompt diagnosis and treatment of GAS pharyngitis are cornerstones of the Rheumatic Fever Prevention Programme, but these are hindered by the turnaround time of culture. Tests with excellent performance and rapid turnaround times are needed. For this study, throat swabs (Copan ESwabs) were collected from schoolchildren self-identifying with a sore throat. Samples were tested by routine culture and the illumigene GAS assay using loop-mediated isothermal amplification. Discrepant results were resolved by retesting of the same specimen by an alternative molecular assay. Seven hundred fifty-seven throat swab specimens were tested by both methods. The performance characteristics of the illumigene assay using culture on blood agar as the "gold standard" and following discrepancy analysis were as follows: sensitivity, 82% and 87%, respectively; specificity, 93% and 98%, respectively; positive predictive value, 61% and 88%, respectively; and negative predictive value, 97% and 97%, respectively. In our unique setting of a school-based throat swabbing program, the illumigene assay did not perform quite as well as described in previous reports. Despite this, its improved sensitivity and rapid turnaround time compared with those of culture are appealing.

Association study involving polymorphisms in IL-6, IL-1RA, and CTLA4 genes and rheumatic heart disease in New Zealand population of Maori and Pacific ancestry.

INTRODUCTION: Rheumatic fever (RF) incidence among New Zealand (NZ) individuals of Polynesian (Maori and Pacific) ancestry remains among the highest in the world. Polymorphisms in the IL-6, IL1RN, and CTLA4 genes have been associated with RF, and their products are modulated by new medications. Confirmation of these previous associations could help guide clinical approaches. We aimed to test IL-6, IL-1RA (IL1RN), and CTLA4 functional SNPs in 204 rheumatic heart disease (RHD) patients and 116 controls of Maori and Pacific ancestry. MATERIAL AND METHOD: Self-reported ancestry of the eight great-grandparents defined ancestry of participants. Severity of carditis was classified according to the 2012 World Heart Federation guideline for the echocardiographic diagnosis of RHD. The IL-6 promoter rs1800797, IL1RN rs447713 and CTLA4 rs3087243 SNPs were genotyped by Taqman. Correlations were assessed by logistic regression analysis adjusting for gender and ancestry. RESULTS: The IL-6 rs1800797 variant was significantly associated with RHD with carriers of the GG genotype 6.09 (CI 1.23; 30.23) times more likely to develop RHD than the carriers of the AA genotype (P=0.027). No significant associations with RHD were found for the IL1RN rs447713 and CTLA4 rs3087243 SNPs. Patients carrying the G allele (GG plus AG genotype) for the IL1RN rs447713 SNP had 2.36 times (CI 1.00; 5.56) more severe carditis than those without this allele (the AA genotype) (P=0.049). CONCLUSION: The IL-6 promoter rs1800797 (-597G/A) SNP may influence susceptibility to RHD of people of Maori and Pacific ancestry living in NZ. The IL1RN rs447713 SNP may influence the severity of carditis in this population.

Early-onset neonatal group B streptococcus sepsis following national risk-based prevention guidelines.

BACKGROUND: Neonatal infection with group B streptococcus (GBS) is an important cause of infant mortality. Intrapartum antibiotics reduce early-onset GBS sepsis, but recommendations vary as to whether they should be offered following antenatal screening or based on risk factors alone. We aimed to determine the incidence of early-onset GBS sepsis in New Zealand five years after the publication of national risk-based GBS prevention guidelines. MATERIALS AND METHODS: Prospective surveillance of early-onset GBS sepsis (defined as infection in the first 48 h of life) was undertaken between April 2009 and March 2011 through the auspices of the New Zealand Paediatric Surveillance Unit as part of a survey of infection presenting in the first week of life. RESULTS: There were 29 cases of confirmed early-onset GBS sepsis, including one case of meningitis, giving an incidence rate of 0.23 per 1000 (95% CI 0.16-0.33) live births. Three infants (10.3%) died. In 16 cases (55%), a maternal risk factor qualifying the mother for intrapartum antibiotics was present, but only five (31%) received this intervention. A retrospective review of the major hospital laboratory databases for this period identified two additional cases. A secondary sensitivity analysis taking account of these cases provided an estimated national incidence of 0.26 (95% CI 0.18-0.37) per 1000 live births. CONCLUSIONS: Ten years after a similar survey and five years after promoting a single, risk-based prevention protocol nationally, the incidence of early-onset GBS disease in New Zealand has more than halved, but opportunities remain to further reduce the rate.

Septic arthritis and acute rheumatic fever in children: the diagnostic value of serological inflammatory markers.

INTRODUCTION: Joint pain and raised inflammatory markers are features of both acute rheumatic fever (ARF) and septic arthritis, often posing a diagnostic challenge to clinicians. Important differences in the presenting serological inflammatory marker profile may assist patient diagnosis, however, as clinical experience suggests that ARF is associated with a higher erythrocyte sedimentation rate (ESR), whereas other serological markers may be similarly elevated in these 2 conditions. OBJECTIVE: The goal of this study was to determine the diagnostic value of serological inflammatory markers and white cell count (WCC) in children presenting with acute joint pain secondary to ARF or septic arthritis. METHODS: Data were obtained from the Auckland regional rheumatic fever database and hospital computer records between 2005 and 2012. Records of all patients under the age of 16 years who were admitted with a new diagnosis of ARF or septic arthritis were analyzed. The diagnosis of ARF was defined on the basis of the New Zealand modification of the Jones Criteria, and the diagnosis of septic arthritis was defined on the basis of joint fluid cytology and culture. Baseline characteristics, serological inflammatory markers, and serum WCC were compared between the ARF and septic arthritis patient groups. RESULTS: Children with ARF displayed significantly higher ESR, higher serum C-reactive protein, and lower serum WCC than children with septic arthritis on presentation to hospital. In children presenting with monoarthritis, an ESR>64.5, serum WCC<12.1×109/L, and age above 8.5 years were found to be significant independent predictors of ARF. Children with all 3 predictors had a 71% risk for ARF and a 29% risk for septic arthritis. A significant proportion (30%) of children with the final diagnosis of ARF initially presented with monoarthritis; 14% of these children (5/34) had received nonsteroidal anti-inflammatory medication before hospital presentation, and 74% of these children (25/34) had abnormal echocardiograms on admission. CONCLUSIONS: ARF and septic arthritis are important diagnoses to consider in children presenting with acute joint pain in New Zealand. A significant proportion of patients with ARF initially present with acute monoarthritis. Serological inflammatory markers and WCC on presentation differ significantly between children with ARF and septic arthritis.

Prospective population-based study on the burden of disease from post-streptococcal glomerulonephritis of hospitalised children in New Zealand: epidemiology, clinical features and complications.

AIM: A nationwide 24-month study was conducted (2007-2009), via the New Zealand Paediatric Surveillance Unit to define epidemiology and clinical features of acute poststreptococcal glomerulonephritis (APSGN) in children hospitalised with the illness. METHODS: Paediatricians (n = 215) were requested to report new hospitalised cases fulfilling a case definition of definite (haematuria with low C3 and high streptococcal titres or biopsy proven APSGN) or probable (haematuria with low C3 or high streptococcal titres). RESULTS: A total of 176 cases were identified (definite: n = 138, probable: n = 38) with 63% residing in the Auckland metropolitan region. Sixty-seven percent were in the most deprived quintile. Annual incidence (0-14 years) was 9.7/100,000 (Pacific 45.5, Maori 15.7, European/other 2.6 and Asian 2.1/100,000). Annual incidence was highest in the South Auckland Metropolitan region (31/100,000), Central Auckland 14.9, West/North Auckland metropolitan region 5.9 and for the remainder of New Zealand 5.5/100,000. Age-specific incidence was highest in age 5-9 years (15.1/100,000). Reduced serum complement C3, gross haematuria, hypertension, impairment of renal function and heavy proteinuria were present in 93%, 87%, 72%, 67% and 44% of patients, respectively. Severe hypertension was closely associated with either symptoms of an acute encephalopathy or congestive heart failure. CONCLUSIONS: New Zealand children carry a significant disease burden of hospitalised APSGN with socio-economically deprived; Pacific and Maori children are being over-represented. Significant short-term complications were observed in hospitalised children with APSGN. Persistently very low rates in European/other suggest a preventable disease.

Reducing inequalities with vaccines: New Zealand's MeNZB vaccine initiative to control an epidemic.

Disadvantaged children of Maori and Pacific origin in New Zealand carry an inequitable burden of infectious diseases, many of which are preventable, some by vaccine. Immunisation is recognised in the developing world as a cheap, effective and efficient means of reducing inequalities. The MeNZB immunisation programme delivered in 2004-2006 towards the expected natural end of a projected 15-year epidemic appears to have had an effect (difficult to prove conclusively) on reducing the disproportionate burden of meningococcal disease carried by this group of children. It was delayed by the late engagement of the New Zealand Ministry of Health, fully briefed from 1996, leading to unnecessary and potentially avoidable deaths and sequelae, many lifelong. Further, failure to adequately assess vaccine effectiveness means that the contribution of MeNZB to the observed reduction in disease, particularly in those aged less than five years, will never be reliably known. However, the MeNZB campaign has at least left a legacy: the National Immunisation Register, which should enable New Zealand to minimise the 'vaccine inverse care law' and contribute to reducing ethnic inequity in the burden of vaccine preventable diseases.

Mortality and hospitalisation costs of rheumatic fever and rheumatic heart disease in New Zealand.

AIMS: To estimate the annual mortality and the cost of hospital admissions for acute rheumatic fever (ARF) and rheumatic heart disease (RHD) for New Zealand residents. METHODS: Hospital admissions in 2000-2009 with a principal diagnosis of ARF or RHD (ICD9_AM 390-398; ICD10-AM I00-I099) and deaths in 2000-2007 with RHD as the underlying cause were obtained from routine statistics. The cost of each admission was estimated by multiplying its diagnosis-related group (DRG) cost weight by the national price for financial year 2009/2010. RESULTS: There were on average 159 RHD deaths each year with a mean annual mortality rate of 4.4 per 100, 000 (95% confidence limit 4.2, 4.7). Age-adjusted mortality was five- to 10-fold higher for Maori and Pacific peoples than for non-Maori/Pacific. The mean age at RHD death (male/female) was 56.4/58.4 for Maori, 50.9/59.8 for Pacific and 78.2/80.6 for non-Maori, non-Pacific men and women. The average annual DRG-based cost of hospital admissions in 2000-2009 for ARF and RHD across all age groups was $12.0 million (95% confidence limit $11.1 million, $12.8 million). Heart valve surgery accounted for 28% of admissions and 71% of the cost. For children 5-14 years of age, valve surgery accounted for 7% of admissions and 27% of the cost. Two-thirds of the cost occurs after the age of 30. CONCLUSIONS: ARF and RHD comprise a burden of mortality and hospital cost concentrated largely in middle age. Maori and Pacific RHD mortality rates are substantially higher than those of non-Maori/Pacific.

Incidence of acute rheumatic fever in New Zealand children and youth.

AIM: To estimate acute rheumatic fever (ARF) incidence rates for New Zealand children and youth by ethnicity, socioeconomic deprivation and region. METHODS: National hospital admissions with a principal diagnosis of ARF (ICD9_AM 390-392; ICD10-AM I00-I02) were obtained from routine statistics and stratified by age, ethnicity, socioeconomic deprivation index (NZDep2006) and District Health Board (DHB). RESULTS: The mean incidence rate for ARF in 2000-2009 peaked at 9 to 12 years of age. Incidence rates for children 5 to 14 years of age for Maori were 40.2 (95% confidence interval 36.8, 43.8), Pacific 81.2 (73.4, 89.6), non-Maori/Pacific 2.1 (1.6, 2.6) and all children 17.2 (16.1, 18.3) per 100 000. Maori and Pacific incidence rates increased by 79% and 73% in 1993-2009, while non-Maori/Pacific rates declined by 71%. Overall rates increased by 59%. In 2000-2009, Maori and Pacific children comprised 30% of children 5-14 years of age but accounted for 95% of new cases. Almost 90% of index cases of ARF were in the highest five deciles of socioeconomic deprivation and 70% were in the most deprived quintile. A child living in the most deprived decile has about one in 150 risk of being admitted to the hospital for ARF by 15 years of age. Ten DHBs containing 76% of the population 5 to 14 years of age accounted for 94% of index cases of ARF. CONCLUSIONS: ARF with its attendant rheumatic heart disease is an increasing public health issue for disadvantaged North Island communities with high concentrations of Maori and/or Pacific families.

Risk factors for acute rheumatic fever: A case-control study.

Background: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain an inequitable cause of avoidable suffering and early death in many countries, including among Indigenous Maori and Pacific populations in New Zealand. There is a lack of robust evidence on interventions to prevent ARF. This study aimed to identify modifiable risk factors, with the goal of producing evidence to support policies and programs to decrease rates of ARF. Methods: A case-control study was undertaken in New Zealand using hospitalised, first episode ARF cases meeting a standard case-definition. Population controls (ratio of 3:1) were matched by age, ethnicity, socioeconomic deprivation, location, sex, and recruitment month. A comprehensive, pre-tested questionnaire was administered face-to-face by trained interviewers. Findings: The study included 124 cases and 372 controls. Multivariable analysis identified strong associations between ARF and household crowding (OR 3·88; 95%CI 1·68-8·98) and barriers to accessing primary health care (OR 2·07; 95% CI 1·08-4·00), as well as a high intake of sugar-sweetened beverages (OR 2·00; 1·13-3·54). There was a marked five-fold higher ARF risk for those with a family history of ARF (OR 4·97; 95% CI 2·53-9·77). ARF risk was elevated following self-reported skin infection (aOR 2·53; 1·44-4·42) and sore throat (aOR 2·33; 1·49-3·62). Interpretation: These globally relevant findings direct attention to the critical importance of household crowding and access to primary health care as strong modifiable causal factors in the development of ARF. They also support a greater focus on the role of managing skin infections in ARF prevention. Funding: This research was funded by the Health Research Council of New Zealand (HRC) Rheumatic Fever Research Partnership (supported by the New Zealand Ministry of Health, Te Puni Kokiri, Cure Kids, Heart Foundation, and HRC) award number 13/959.

Invasive group A streptococcal infection and vaccine implications, Auckland, New Zealand.

We aimed to assess the effect of invasive group A streptococcal (GAS) infection and the potential effects of a multivalent GAS vaccine in New Zealand. During January 2005-December 2006, we conducted prospective population-based laboratory surveillance of Auckland residents admitted to all public hospitals with isolation of GAS from normally sterile sites. Using emm typing, we identified 225 persons with confirmed invasive GAS infection (median 53 years of age; range 0-97 years). Overall incidence was 8.1 cases per 100,00 persons per year (20.4/100,000/year for Maori and Pacific Islanders; 24.4/100,000/year for persons >65 years of age; 33/100,000/year for infants <1 year of age). Nearly half (49%) of all cases occurred in Auckland's lowest socioeconomic quintile. Twenty-two persons died, for an overall case-fatality rate of 10% (63% for toxic shock syndrome). Seventy-four percent of patients who died had an underlying condition. To the population in our study, the proposed 26-valent vaccine would provide limited benefit.

Rheumatic fever recurrence prevention: a nurse-led programme of 28-day penicillin in an area of high endemnicity.

AIMS: To evaluate safety and effectiveness of 28-day long-acting penicillin to prevent recurrences of acute rheumatic fever (ARF). METHODS: Historical cohort study using the regional RF register for Auckland, New Zealand, in a 5-14-year-old population with ARF rates of ~40-80/100,000. Consented patients were referred to a population-based delivery programme of free benzathine penicillin every 28 days by community nurses with discharge after the longer of 10 years of treatment or aged 21 years. First-episode and recurrent ARF cases classified as definite (Jones criteria 1992) or probable (Jones criteria 1956) were the main outcome measures. RESULTS: Of the 360 cases meeting the case definitions, 20 recurrences occurred in 19 people (median age 21 years). The age at first episode was 2-52 years (mode 11 years), median age 21.3 (8-40). ARF recurred 0-21 years after penicillin was discontinued. Seventy-two per cent of recurrent cases occurred within 5 years, and 12% between 5 years and 10 years. The 4-weekly long-acting penicillin failure rate (n= 1) was 0.07/100 patient years. The programme failure rate (Auckland residents) was 1.4/100 patient years (n= 20). Patient non-adherence accounted for 55% of recurrences. Two recurrences after discharge from prophylaxis as per the New Zealand guidelines occurred 3 years and 13 years later. CONCLUSIONS: In this environment, 28-day long-acting penicillin prophylaxis for at least 10 years delivered by community nurses is safe and effective for patients with no or mild cardiac disease by auscultation at discharge off penicillin. Penicillin delivery every 21 days (as suggested by a recent Cochrane review) would add to costs and complexity.

Optimising echocardiographic screening for rheumatic heart disease in New Zealand: not all valve disease is rheumatic.

AIMS: Echocardiography detects a greater prevalence of rheumatic heart disease than heart auscultation. Echocardiographic screening for rheumatic heart disease combined with secondary prophylaxis may potentially prevent severe rheumatic heart disease in high-risk populations. We aimed to determine the prevalence of rheumatic heart disease in children from an urban New Zealand population at high risk for acute rheumatic fever. METHODS AND RESULTS: To optimise accurate diagnosis of rheumatic heart disease, we utilised a two-step model. Portable echocardiography was conducted on 1142 predominantly Maori and Pacific children aged 10-13 years. Children with an abnormal screening echocardiogram underwent clinical assessment by a paediatric cardiologist together with hospital-based echocardiography. Rheumatic heart disease was then classified as definite, probable, or possible. Portable echocardiography identified changes suggestive of rheumatic heart disease in 95 (8.3%) of 1142 children, which reduced to 59 (5.2%) after cardiology assessment. The prevalence of definite and probable rheumatic heart disease was 26.0 of 1000, with 95% confidence intervals ranging from 12.6 to 39.4. Portable echocardiography overdiagnosed rheumatic heart disease with physiological valve regurgitation diagnosed in 28 children. A total of 30 children (2.6%) had non-rheumatic cardiac abnormalities, 11 of whom had minor congenital mitral valve anomalies. CONCLUSIONS: We found high rates of undetected rheumatic heart disease in this high-risk population. Rheumatic heart disease screening has resource implications with cardiology evaluation required for accurate diagnosis. Echocardiographic screening for rheumatic heart disease may overdiagnose rheumatic heart disease unless congenital mitral valve anomalies and physiological regurgitation are excluded.

The primary prevention of rheumatic fever.

Rheumatic fever (RF), caused by untreated group A streptococcal (GAS) pharyngitis, is a major cause of morbidity and mortality throughout much of the less developed world and disadvantaged populations (Indigenous and other) in the developed world. Through systematic literature searches, our group has identified potential risk factors for RF and possible interventions for its prevention. The causes can be divided into biological factors, socio-economic, and lifestyle factors and health-care systems and services. Currently, the most promising medical areas look to be improving access to health care and introducing community and school-based sore throat interventions (which aim to diagnose and treat GAS pharyngitis). We could find no convincing support for skin sepsis causing RF. Overall evidence suggests that measures that aim to alleviate poverty and crowding may also reduce the incidence of RF. In comparatively rich countries such as New Zealand and Australia, urgent measures based on available evidence should be undertaken to reduce the very striking health disparity seen with RF and its sequela, rheumatic heart disease in our at-risk populations.

School-based Streptococcal A Sore-throat Treatment Programs and Acute Rheumatic Fever Amongst Indigenous Maori: A Retrospective Cohort Study.

BACKGROUND: Acute rheumatic fever (ARF) predominantly affects indigenous Maori schoolchildren in Bay of Plenty region, and more so male Maori students, especially when socioeconomically deprived. We evaluated the effectiveness of strategies for reducing ARF with group A streptococcal pharyngitis treatment in 2011-18. METHODS: We retrospectively assessed outcomes of 3 open cohorts of Maori schoolchildren receiving different interventions: Eastern Bay rural Cohort 1, mean deprivation decile 9.80, received school-based sore-throat programs with nurse and general practice (GP) support; Eastern Whakatane township/surrounds Cohort 2, mean deprivation 7.25, GP management; Western Bay Cohort 3, mean deprivation 5.98, received predominantly GP care, but 3 highest-risk schools received school-based programs. Cases were identified from ICD10 ARF-coded hospital discharges, notifications to Ministry of Health, and a secondary-prevention penicillin database. Primary outcomes were first-presentation ARF cohorts' incidence preintervention (2000-10) and postintervention (2011-18) with cases over annual school rolls' Maori students-year denominators. RESULTS: Overall, ARF in Maori schoolchildren declined in the cohorts with school-based programs. Cohort 1 saw a postintervention (2011-18) decline of 60%, 148 to 59/100,000/year, rate ratio (RR) = 0.40(CI 0.22-0.73) P = 0.002. Males' incidence declined 190 to 78 × 100,000/year RR = 0.41(CI 0.19-0.85) P = 0.013 and females too, narrowing gender disparities. Cohort 3 ARF incidence decreased 48%, 50 to 26/100,000/year RR = 0.52(CI 0.27-0.99) P = 0.044. In contrast, ARF doubled in Cohort 2 students with GP-only care without school-based programs increasing 30 to 69/100,000/year RR = 2.28(CI 0.99-5.27) P = 0.047, especially for males 39/100,000/year to 107/100,000/year RR = 2.71(CI 1.00-7.33) P = 0.0405. CONCLUSIONS: School-based programs with indigenous Maori health workers' sore-throat swabbing and GP/Nurse support reduced first-presentation ARF incidence in Maori students in highest-risk settings.

Fast tracking the vaccine licensure process to control an epidemic of serogroup B meningococcal disease in New Zealand.

Epidemics of serogroup B meningococcal disease are rare. Strain-specific outer membrane vesicle vaccines, which are not marketed, are the only current tool for control. A correlate of protection is ill defined, but published data suggest that measured serum bactericidal antibody levels parallel efficacy. Even infants can mount a strain-specific antibody response to a strain-specific vaccine. New Zealand's epidemic (1991-2007; peak rate [in 2001], 17.4 cases per 100,000 persons) was dominated by a single strain. After a 5-year search (1996-2001) for a manufacturer for a strain-specific outer membrane vesicle vaccine, a fast-tracked research program (2002-2004) determined the safety and immunogenicity of vaccine in infants (2 age groups: 6-10 weeks and 6-8 months), children (age, 16-24 months), and school-aged children (age, 8-12 years) after an adult trial. The vaccine was reactogenic, compared with control vaccines (meningococcal C conjugate and routine infant vaccines), but retention was high. Three vaccine doses produced antibody levels (measured by serum bactericidal assay) that were considered to be adequate for public health intervention. However, in young infants, a fourth dose was required to achieve levels equivalent to those achieved by other age groups. Provisional licensure by New Zealand's MedSafe was based on serological criteria strengthened by bridged safety data from studies of the parent outer membrane vesicle vaccine, independent assessment of manufacturing quality, and a clear plan for safety monitoring and effectiveness evaluation after licensure.

Immunogenicity and tolerability in infants of a New Zealand epidemic strain meningococcal B outer membrane vesicle vaccine.

BACKGROUND: An outer membrane vesicle meningococcal vaccine (MeNZB), was developed for the New Zealand epidemic strain of Neisseria meningitidis B:4:P1.7-2,4. METHODS: A phase II, randomized, observer blind, controlled study evaluating the safety, reactogenicity, and immunogenicity of MeNZB administered with routine New Zealand immunizations at 6 weeks, 3 months, and 5 months of age (n = 375). Group 1 (n = 250) received 25 mug MeNZB and routine immunizations with a fourth MeNZB dose given at 10 months (n = 51). Group 2 (n = 125) received routine immunizations only. Sero-response was a > or =4-fold rise in vaccine strain serum bactericidal antibody titer compared with baseline or a titer of at least 1:8 for baselines <1:4. Reactogenicity was monitored for 7 days after vaccination. RESULTS: Sero-response in Group 1 was achieved in 53% (95% Confidence interval [CI]: 46-59, n = 239) and 69% (95% CI: 54-80, n = 45) with geometric mean antibody titers of 9 (95% CI: 7-10) and 22 (95% CI: 12-39) after the third and fourth doses, respectively. No negative interference by MeNZB on routine immunizations was detected. There were no serious adverse events judged to be vaccine related. CONCLUSIONS: In this group of New Zealand infants, 4 MeNZB doses were required to demonstrate titers comparable with those achieved after 3 doses in older children. MeNZB was safe when used concomitantly with routine New Zealand immunizations to 5 months of age.