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.

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.

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.

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.

Risk Factors for Acute Rheumatic Fever: Literature Review and Protocol for a Case-Control Study in New Zealand.

Acute rheumatic fever (ARF) and its sequela, rheumatic heart disease (RHD), have largely disappeared from high-income countries. However, in New Zealand (NZ), rates remain unacceptably high in indigenous Maori and Pacific populations. The goal of this study is to identify potentially modifiable risk factors for ARF to support effective disease prevention policies and programmes. A case-control design is used. Cases are those meeting the standard NZ case-definition for ARF, recruited within four weeks of hospitalisation for a first episode of ARF, aged less than 20 years, and residing in the North Island of NZ. This study aims to recruit at least 120 cases and 360 controls matched by age, ethnicity, gender, deprivation, district, and time period. For data collection, a comprehensive pre-tested questionnaire focussed on exposures during the four weeks prior to illness or interview will be used. Linked data include previous hospitalisations, dental records, and school characteristics. Specimen collection includes a throat swab (Group A Streptococcus), a nasal swab (Staphylococcus aureus), blood (vitamin D, ferritin, DNA for genetic testing, immune-profiling), and head hair (nicotine). A major strength of this study is its comprehensive focus covering organism, host and environmental factors. Having closely matched controls enables the examination of a wide range of specific environmental risk factors.

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.

Is a rheumatic fever register the best surveillance tool to evaluate rheumatic fever control in the Auckland region?

AIM: To determine the most accurate data source for acute rheumatic fever (ARF) epidemiology in the Auckland region. METHOD: To assess coverage of the Auckland Regional Rheumatic Fever Register (ARRFR), (1998-2010) for children <15 years and resident in Auckland at the time of illness, register, hospitalisation and notification data were compared. A consistent definition was applied to determine definite and probable cases of ARF using clinical records. (www.heartfoundation.org.nz) RESULTS: Of 559 confirmed (definite and probable) RF cases <15 years (median age 10 years), seven were recurrences. Of 552 first episodes, the ARRFR identified 548 (99%), hospitalisations identified 501 (91%) including four not on the register, and public health notifications identified 384 (70%). Of hospitalisation cases, 33% (245/746), and of notifications 20% (94/478) did not meet the case definition and were therefore excluded. Between 1998-2010, eight cases, initially entered as ARF on the ARRFR, were later removed once further clinical detail was available. CONCLUSION: The ARRFR produced the most accurate information surrounding new cases of ARF (for children <15 years) for the years 1998-2010 in Auckland. This was significantly more accurate than medical officer of health notification and hospitalisation data.

Adequate adherence to benzathine penicillin secondary prophylaxis following the diagnosis of rheumatic heart disease by echocardiographic screening.

AIMS: The primary aim of this study was to determine adherence to benzathine penicillin (BPG) for individuals diagnosed with rheumatic heart disease (RHD) by echocardiographic screening between 2007-2012. METHODS: BPG records were obtained for 57 patients, median age 12 at time of diagnosis. A 'days at risk' analysis was undertaken. Annual adherence was calculated for each individual. A comparison with the Wellington region's Rheumatic Fever 2013 adherence data was undertaken. RESULTS: Adherence to BPG was good with a median follow-up time of 5.8 years. Days at risk analysis: median 0% at year one and 2.7% at year five. The median adherence for the entire cohort over the entire follow-up period was 92%, range 0-100%. There was no difference of proportions of late doses compared to the Wellington region. Median adherence was higher for register based (94%, n=48) compared to primary health care penicillin delivery (37%, n=7), p<0.005. During follow-up, 30% of the cohort moved between regions or overseas. CONCLUSIONS: Good adherence rates are achievable for secondary prophylaxis when RHD is diagnosed by echocardiographic screening. This likely reflects the benefit of rheumatic fever registers and community nursing services rather than the pathway of the diagnosis for RHD.

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.

First Presentation Acute Rheumatic Fever is Preventable in a Community Setting: A School-based Intervention.

BACKGROUND: Robust evidence is lacking for community initiatives to prevent first presentation acute rheumatic fever (ARF) by group A streptococcal (GAS) pharyngitis treatment. METHODS: We measured the effect of introducing a sore throat clinic program on first presentation ARF into 61-year 1-8 schools with students 5-13 years of age (population ≈25,000) in Auckland, New Zealand. The study period was 2010-2016. A generalized linear mixed model investigated ARF rate changes before and after the staggered introduction of school clinics. Nurses and lay workers treated culture-proven GAS sore throats (including siblings) with 10 days of amoxicillin. ARF cases were identified from a population-based secondary prophylaxis register. Annual pharyngeal GAS prevalence was assessed in a subset. RESULTS: ARF rates in 5-13 year olds dropped from 88 [95% confidence interval (CI): 79-111] per 100,000 preclinics to 37 (95% CI: 15-83) per 100,000 after 2 years of clinic availability, a 58% reduction. No change in rate was demonstrated before the introduction of clinics [P = 0.88; incidence risk ratio for a 1-year change: 0.98 (95% CI: 0.63-1.52)], but there was a significant decrease of first presentation ARF rates with time after the introduction of the sore throat program [P = 0.008; incidence risk ratio: 0.61 (95% CI: 0.43-0.88)]. Pharyngeal GAS cross-sectional prevalence fell from 22.4% (16.5-30.5) preintervention to 11.9% (8.6-16.5) and 11.4% (8.2-15.7) 1 or 2 years later (P = 0.005). CONCLUSIONS: ARF declined significantly after school-based GAS pharyngitis management using oral amoxicillin paralleled by a decline in pharyngeal GAS prevalence.

Proposed new industry code on unhealthy food marketing to children and young people: will it make a difference?

Reducing the exposure of children and young people to the marketing of unhealthy foods is a core strategy for reducing the high overweight and obesity prevalence in this population. The Advertising Standards Authority (ASA) has recently reviewed its self-regulatory codes and proposed a revised single code on advertising to children. This article evaluates the proposed code against eight criteria for an effective code, which were included in a submission to the ASA review process from over 70 New Zealand health professors. The evaluation found that the proposed code largely represents no change or uncertain change from the existing codes, and cannot be expected to provide substantial protection for children and young people from the marketing of unhealthy foods. Government regulations will be needed to achieve this important outcome.

Where to from here? The treatment of impetigo in children as resistance to fusidic acid emerges.

Admissions for skin and soft-tissue infections have been increasing steadily in children and in the general population. Concerns have been raised recently about the increasing widespread use of topical fusidic acid and concurrent increase of fusidic acid-resistant Staphylococcus aureus. Fusidic acid resistance and methicillin resistant Staphylococcus aureus (MRSA) are both more prevalent in youngest age group (<5 year-olds) and particularly in the North island. In New Zealand, fusidic acid is recommended for treatment of minor impetigo and is the only fully-funded topical antibiotic. The evidence base for alternative treatment strategies for mild impetigo is limited. Most children with impetigo in the current Counties Manukau skin and sore throat schools programme received care with wound management with only a few requiring escalation. An upcoming randomised controlled trial comparing topical hydrogen peroxide cream, topical fusidic acid and wound management only (clean and cover) will help provide evidence about the effectiveness of alternative treatments in the New Zealand setting.

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.

Nurse-led school-based clinics for rheumatic fever prevention and skin infection management: evaluation of Mana Kidz programme in Counties Manukau.

AIM: To evaluate registered nurse-led school clinics in 61 primary and intermediate schools in Counties Manukau. METHODS: The evaluation (conducted August­December, 2014) collated evidence concerning service delivery, outcomes, value for money and effectiveness. RESULTS: 97% (23,756/24,497) of eligible children were consented, 11% (20,696/191,423) of throat swabs taken (February 2013­September 2014) were culture positive for Group A Streptococcus (GAS); 20,176 were treated. Mana Kidz teams treated (includes cleaning and covering alone) 17,593 skin infections and actioned 4,178 school health referrals. A pre-programme cross sectional GAS pharyngeal prevalence demonstrated a relative risk 1.8 (1.3­2.3) (95%CI) of being pharyngeal GAS positive in 2013 compared to 2014. Hospitalisations for acute rheumatic fever (ARF) and skin infections for children aged 5­12 years living in Counties Manukau are declining and this appears to be temporally related to the introduction of the Mana Kidz programme. Effective engagement with children, parents/ whanau and improved health literacy was demonstrated, especially knowledge about sore throats, ARF, medication adherence and skin infection. The programme was delivered at $280 per participating child in the 2013/14 financial year. CONCLUSION: Mana Kidz is an effective programme with a substantial contribution to health care for children, aged 5­12 years, identified at increased risk of poor health outcomes.

Antimicrobial stewardship using pharmacy data for the nurse-led school-based clinics in Counties Manukau District Health Board for management of group A streptococcal pharyngitis and skin infection.

AIM: To evaluate antimicrobial usage in the school-based clinics against operating guidelines. METHOD: Antimicrobial prescribing data (2014) from 10/18 participating pharmacies serving 14,153/23,588 primary school children of the programme were accessible. Prescriptions from 5/10 pharmacies were available for identifying type, amount, and indication of the medicine. One pharmacy serving a defined population (n=3,513) with single healthcare provider delivering the school programme was selected for detailed evaluation and identifying individuals receiving multiple treatments. RESULTS: Data from 10 pharmacies (n=7,889 prescriptions) showed 91.2% of prescriptions were for group A streptococcal-positive throat swab, 8.8% for skin infections. More detail from 5/10 pharmacies showed only 2% of group A streptococcal pharyngitis treatments (107/4,672) were not first-line (56 cephalexin and 51 rifampin prescriptions). Fusidic acid (159/452, 35.18%) or cephalexin (169/452, 37.39%) were most commonly used for skin infection. Analysis in the defined population showed <4% (151/4,325) of assessed skin conditions received antimicrobials, and only 6 individuals received more than one course of oral antimicrobial over the year. CONCLUSION: Antimicrobial administration demonstrates high compliance with the protocol. There was very limited use of second-line antimicrobials for recurrent pharyngitis. Most skin infections did not require antimicrobial treatment. Repeated antimicrobials for individuals were rare.

Persistence, Discordance and Diversity of Staphylococcus aureus Nasal and Oropharyngeal Colonization in School-aged Children.

BACKGROUND: The anterior nares are regarded as the primary site for Staphylococcus aureus colonization, although studies have highlighted the potential importance of colonization at extra-nasal sites, including the oropharynx. Accordingly, the aims of this study were to assess the prevalence, persistence and molecular epidemiology of S. aureus colonization in the nares and oropharynx of Maori and Pacific children, a population with strikingly high rates of S. aureus infection. METHODS: A cross-sectional study of predominantly Maori and Pacific school-aged children in Auckland, New Zealand was performed in October 2013, and swabs were taken from the nares and oropharynx. Sampling was repeated from the same schools in October 2014. All S. aureus isolates underwent antimicrobial susceptibility testing and spa typing. RESULTS: Overall, 506/893 (56.7%) children were colonized with S. aureus, and the colonization prevalence was significantly higher in the oropharynx than nares (41.1% vs. 31.5%; P < 0.001). Longitudinal colonization was significantly higher in the oropharynx than the nares, and children with longitudinal oropharyngeal colonization were more likely to be colonized with the same spa type than those colonized in the nares (67.6% vs. 37.0%; P = 0.01). Approximately 40% of children had discordant spa types at the nares and oropharynx. CONCLUSIONS: Oropharyngeal S. aureus colonization represents a significant reservoir of S. aureus and it is possible that the oropharynx may represent a protected anatomical niche, enabling persistent colonization with the same S. aureus strain. Future study should attempt to better understand the determinants of oropharyngeal carriage.

Seven key actions to eradicate rheumatic heart disease in Africa: the Addis Ababa communiqué.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major causes of heart failure, stroke and death among African women and children, despite being preventable and imminently treatable. From 21 to 22 February 2015, the Social Cluster of the Africa Union Commission (AUC) hosted a consultation with RHD experts convened by the Pan-African Society of Cardiology (PASCAR) in Addis Ababa, Ethiopia, to develop a 'roadmap' of key actions that need to be taken by governments to eliminate ARF and eradicate RHD in Africa. Seven priority areas for action were adopted: (1) create prospective disease registers at sentinel sites in affected countries to measure disease burden and track progress towards the reduction of mortality by 25% by the year 2025, (2) ensure an adequate supply of high-quality benzathine penicillin for the primary and secondary prevention of ARF/RHD, (3) improve access to reproductive health services for women with RHD and other non-communicable diseases (NCD), (4) decentralise technical expertise and technology for diagnosing and managing ARF and RHD (including ultrasound of the heart), (5) establish national and regional centres of excellence for essential cardiac surgery for the treatment of affected patients and training of cardiovascular practitioners of the future, (6) initiate national multi-sectoral RHD programmes within NCD control programmes of affected countries, and (7) foster international partnerships with multinational organisations for resource mobilisation, monitoring and evaluation of the programme to end RHD in Africa. This Addis Ababa communiqué has since been endorsed by African Union heads of state, and plans are underway to implement the roadmap in order to end ARF and RHD in Africa in our lifetime.