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Jonathan R Carapetis

Publications and source records attributed to Jonathan R Carapetis.

At least 19 recordsLinked to original sources
PubMed2006

Subclinical carditis in rheumatic fever: a systematic review.

OBJECTIVE: Subclinical carditis (SCC)--pathological valvular regurgitation detected on echocardiography that is not evident clinically--has been reported in acute rheumatic fever (ARF), but its significance is unknown. We aimed to review the existing literature on the prevalence and outcome of SCC in ARF. METHODS: We conducted a systematic literature review using MEDLINE. RESULTS: Prevalences of SCC in ARF ranged from 0% (in one study only) to 53% in 23 articles. The weighted pooled prevalence of SCC in ARF was 16.8% (95%CI 11.9 to 21.6). This increased slightly to 18.1% (95%CI 11.1 to 25.2) by analysing only the 10 studies that applied full World Health Organization criteria for SCC diagnosis. The weighted pooled prevalence of persistence or deterioration of SCC 3 to 23 months after ARF diagnosis was 44.7% (95%CI 19.3 to 70.2) from 11 articles. CONCLUSION: SCC is relatively common in ARF. Although some studies suggest that SCC lesions may persist or deteriorate, the available data are insufficient and of poor quality, so no confident conclusions can be drawn about the prognosis of SCC. Until better studies are conducted, clinicians will have to make management decisions that are not evidence-based. These decisions will have important practical implications for the use of echocardiography acutely and during follow-up, diagnosis of ARF, and duration of secondary prophylaxis in patients with SCC.

Acute Disease↗
PubMed2006

Low rates of streptococcal pharyngitis and high rates of pyoderma in Australian aboriginal communities where acute rheumatic fever is hyperendemic.

BACKGROUND: Acute rheumatic fever is a major cause of heart disease in Aboriginal Australians. The epidemiology differs from that observed in regions with temperate climates; streptococcal pharyngitis is reportedly rare, and pyoderma is highly prevalent. A link between pyoderma and acute rheumatic fever has been proposed but is yet to be proven. Group C beta-hemolytic streptococci and group G beta-hemolytic streptococci have also been also implicated in the pathogenesis. METHODS: Monthly, prospective surveillance of selected households was conducted in 3 remote Aboriginal communities. People were questioned about sore throat and pyoderma; swab specimens were obtained from all throats and any pyoderma lesions. Household population density was determined. RESULTS: From data collected during 531 household visits, the childhood incidence of sore throat was calculated to be 8 cases per 100 person-years, with no cases of symptomatic group A beta-hemolytic streptococci pharyngitis. The median point prevalence for throat carriage was 3.7% for group A beta-hemolytic streptococci, 0.7% for group C beta-hemolytic streptococci, and 5.1% for group G beta-hemolytic streptococci. Group A beta-hemolytic streptococci were recovered from the throats of 19.5% of children at some time during the study. There was no seasonal trend or correlation with overcrowding. Almost 40% of children had pyoderma at least once, and the prevalence was greatest during the dry season. In community 1, the prevalence of pyoderma correlated with household crowding. Group C and G beta-hemolytic streptococci were rarely recovered from pyoderma lesions. CONCLUSIONS: These data are consistent with the hypothesis that recurrent skin infections immunize against throat colonization and infection. High rates of acute rheumatic fever were not driven by symptomatic group A beta-hemolytic streptococci throat infection. Group G and C beta-hemolytic streptococci were found in the throat but rarely in pyoderma lesions.

Adolescent↗
PubMed2006

B-cell antigen D8/17 is a marker of rheumatic fever susceptibility in Aboriginal Australians and can be tested in remote settings.

OBJECTIVE: To test the B-cell antigen D8/17 as a marker of past rheumatic fever (RF) in a predominantly Aboriginal Australian population, and to evaluate technical modifications to allow its use in remote settings. DESIGN AND SETTING: Cross-sectional survey in a remote Aboriginal community, a regional tertiary referral hospital and a tertiary paediatric centre in Melbourne. PARTICIPANTS: 106 people, including three with acute RF, 38 with a history of past RF, 20 relatives of these people, and 45 healthy controls. MAIN OUTCOME MEASURE: D8/17 expression in B cells. RESULTS: Blood was collected from each participant and the expression of D8/17 and CD19 in each sample was analysed by flow cytometry. The mean proportion of D8/17-positive B cells was 39.3% (SD, 11.8) in patients with previous RF, 22.5% (SD, 5.2) in first-degree relatives, 11.6% (SD, 7.2) in controls, and 83.7% (SD, 10.1) in patients with acute RF (analysis of variance test between means, P = 0.001). A cut-off of 22.1% of D8/17-positive B cells to indicate past RF yielded the highest percentage of correct results (95.4%). Delayed staining of whole blood (mean, 0.55 days; SD, 0.2) gave equivalent results to immediate staining, but the D8/17 assay on peripheral blood mononuclear cells was unreliable. CONCLUSIONS: The B-cell antigen D8/17 accurately identifies Australians with a past history of RF, and the assay is feasible in remote settings with access to facilities capable of performing D8/17 staining within half a day of sample collection.

Adolescent↗
PubMed2006

Practical challenges of conducting research into rheumatic fever in remote Aboriginal communities.

Before embarking on an epidemiological study of acute rheumatic fever in remote Aboriginal communities, researchers engaged in the processes of community consultation, consent and household enrollment. Community expectations and time constraints are not necessarily those of the funding bodies, and a considerable investment of time and local engagement was required before the project proceeded with local support. The remoteness of the communities, harsh climate and limited infrastructure made working conditions difficult. Nevertheless, the study was completed and the results are being returned to the local councils and households. The research team continues to maintain its relationship with each study community.

Community Participation↗
PubMed2006

Use of a single-nucleotide polymorphism genotyping system to demonstrate the unique epidemiology of methicillin-resistant Staphylococcus aureus in remote aboriginal communities.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem in Australia, as in many other parts of the world. High rates of CA-MRSA skin and soft tissue infection have been reported from Aboriginal communities. We used a single-nucleotide polymorphism (SNP) genotyping typing system based on the multilocus sequence type (MLST) database to investigate the epidemiology of CA-MRSA and methicillin-sensitive S. aureus (MSSA) over a 12-month period in three remote Aboriginal communities of Northern Australia. This was supplemented by real-time PCR for Panton-Valentine leukocidin (PVL) genes, staphylococcal cassette chromosome mec (SCCmec) typing, and antimicrobial susceptibility testing. S. aureus was recovered from pyoderma lesions on 221 occasions and throat swabs on 44 occasions. The median monthly recovery rate of S. aureus from skin sores was 58% (interquartile range, 62 to 78%), and there was no seasonal variation. Twenty-three percent of isolates were CA-MRSA; the proportion was similar across the communities and did not vary over the study period. Erythromycin resistance was found in 47% of CA-MRSA and 21% of MSSA. SNP-based typing identified 14 different clonal complexes (cc); however, cc75 was predominant, accounting for 71% of CA-MRSA isolates. These were confirmed as ST75-like by using an additional SNP and MLST of selected isolates. All but one of the cc75 isolates had SSCmec type IV (one had type V), and all were PVL negative. Monthly tracking of SNP-based cc types showed a highly dynamic process. ST75-MRSA-IV appears to be unique to the region and probably evolved de novo in remote Aboriginal communities.

Australia↗
PubMed2005

The clinical course of acute otitis media in high-risk Australian Aboriginal children: a longitudinal study.

BACKGROUND: It is unclear why some children with acute otitis media (AOM) have poor outcomes. Our aim was to describe the clinical course of AOM and the associated bacterial nasopharyngeal colonisation in a high-risk population of Australian Aboriginal children. METHODS: We examined Aboriginal children younger than eight years who had a clinical diagnosis of AOM. Pneumatic otoscopy and video-otoscopy of the tympanic membrane (TM) and tympanometry was done every weekday if possible. We followed children for either two weeks (AOM without perforation), or three weeks (AOM with perforation), or for longer periods if the infection persisted. Nasopharyngeal swabs were taken at study entry and then weekly. RESULTS: We enrolled 31 children and conducted a total of 219 assessments. Most children had bulging of the TM or recent middle ear discharge at diagnosis. Persistent signs of suppurative OM (without ear pain) were present in most children 7 days (23/30, 77%), and 14 days (20/26, 77%) later. Episodes of AOM did not usually have a sudden onset or short duration. Six of the 14 children with fresh discharge in their ear canal had an intact or functionally intact TM. Perforation size generally remained very small (<2% of the TM). Healing followed by re-perforation was common. Ninety-three nasophyngeal swabs were taken. Most swabs cultured Streptococcus pneumoniae (82%), Haemophilus influenzae (71%), and Moraxella catarrhalis (95%); 63% of swabs cultured all three pathogens. CONCLUSION: In this high-risk population, AOM was generally painless and persistent. These infections were associated with persistent bacterial colonisation of the nasopharynx and any benefits of antibiotics were modest at best. Systematic follow up with careful examination and review of treatment are required and clinical resolution cannot be assumed.

Acute Disease↗
PubMed2005

The global burden of group A streptococcal diseases.

The global burden of disease caused by group A streptococcus (GAS) is not known. We review recent population-based data to estimate the burden of GAS diseases and highlight deficiencies in the available data. We estimate that there are at least 517,000 deaths each year due to severe GAS diseases (eg, acute rheumatic fever, rheumatic heart disease, post-streptococcal glomerulonephritis, and invasive infections). The prevalence of severe GAS disease is at least 18.1 million cases, with 1.78 million new cases each year. The greatest burden is due to rheumatic heart disease, with a prevalence of at least 15.6 million cases, with 282,000 new cases and 233,000 deaths each year. The burden of invasive GAS diseases is unexpectedly high, with at least 663,000 new cases and 163,000 deaths each year. In addition, there are more than 111 million prevalent cases of GAS pyoderma, and over 616 million incident cases per year of GAS pharyngitis. Epidemiological data from developing countries for most diseases is poor. On a global scale, GAS is an important cause of morbidity and mortality. These data emphasise the need to reinforce current control strategies, develop new primary prevention strategies, and collect better data from developing countries.

Glomerulonephritis↗
PubMed2005

Current issues regarding the use of pneumococcal conjugate and polysaccharide vaccines in Australian children.

OBJECTIVE: To present the results of child pneumococcal vaccination studies in the setting of current Australian disease epidemiology and immunization policy, and issues that clinicians should consider in discussions with families. METHODS: This paper includes a narrative review of randomized, controlled, double blind studies and systematic reviews which evaluated the efficacy of child pneumococcal vaccination. RESULTS: 7PCV is expected to prevent > 80% of childhood invasive pneumococcal disease (IPD, includes meningitis, septicaemia/bacteraemia) and the associated mortality. 7PCV may prevent 6% of all pneumonia, 18% of radiographically-defined pneumonia, 6% of all otitis media (OM) and 20%-40% of tympanostomy tube procedures. It may also reduce IPD due to antibiotic-resistant pneumococci, and prevent IPD in unvaccinated individuals. The impact of replacement disease caused by non-vaccine serotypes is not yet known. Pneumococcal polysaccharide vaccines given to 2-year-old children may prevent approximately 19% of all and 26% of recurrent OM. CONCLUSION: The Australian Standard Vaccination Schedule recommends universal infant immunization with seven-valent pneumococcal conjugate vaccine (7PCV). Universal infant 7PCV will prevent pneumococcal diseases and deaths. The potential for its impact to be reduced in the long-term by serotype replacement must be closely monitored. Information concerning disease epidemiology, vaccine efficacy and safety, disease risk perception and national costs may prove useful in discussions with families.

Australia↗
PubMed2004

The burden and cost of hospitalised varicella and zoster in Australian children.

BACKGROUND: Economic analyses of varicella-zoster virus (VZV) immunisation are sensitive to the costs of hospitalised cases, so there is a need to validate VZV hospitalisation data. AIMS: To assess the accuracy of hospital VZV coding data and to apply these parameters to a population-based sample to estimate incidence and costs. METHODS: A 3-year retrospective chart review from one hospital to document clinical features and validate coding data. A separate 9-year analysis of discharge data from two hospitals draining a defined region of suburban Melbourne, with adjustment for miscoding and estimates of direct hospital costs. RESULTS: After correction for miscoding, 224 patients were admitted to one hospital over 3 years, 79% with varicella and 21% with zoster. Miscoding resulted in a 15% underestimate of zoster cases and a 4% overestimate of varicella cases. Thirty-six percent of varicella admissions compared to 80% of zoster admissions were immunocompromised and/or had chronic disease. Compared to otherwise-healthy patients, immunocompromised patients were admitted earlier in their illness and had lower complication rates. Forty-two percent of immunocompromised/chronic disease patients with varicella had a known exposure, usually from a family member. The incidence of hospitalised varicella and zoster in under 15-year olds was 15.7 and 1.8 per 100,000 per year, respectively. This suggests that there are 615 varicella hospitalisations and 72 zoster hospitalisations in this age group each year in Australia, at a total direct cost of over 2.2 million AU dollars. CONCLUSION: These results highlight the considerable burden of hospitalised zoster and the importance of immunising non-immune contacts of immunocompromised individuals. They also support previous estimates of the incidence of hospitalised varicella in Australian children and adolescents, although direct medical costs may be higher than those previously estimated.

Adolescent↗
PubMed2004

Group A streptococci from a remote community have novel multilocus genotypes but share emm types and housekeeping alleles with isolates from worldwide sources.

Group A streptococci (GAS) cause several human diseases that differentially affect distinct host populations. Genotypes were defined by multilocus sequence typing and emm typing for 137 organisms collected from individuals in a remote aboriginal island community in tropical Australia and compared with >200 isolates obtained from sources elsewhere in the world. The majority of aboriginal-derived isolates shared emm types and housekeeping alleles with GAS isolates recovered from outside Australia, but these emm types and alleles were in novel combinations. There were many examples in which isolates from aboriginal and non-Australian subjects shared the same emm type, but for approximately 50% of emm types, the multilocus genotypes of isolates of the same emm type but from different regions were very different. A single emm type may typically define a single clone within the United States and on the remote island that is the focus of this study, but in many cases, these clones will be different, and this finding has implications for attempts to make global associations between emm types and certain disease manifestations.

Australia↗
PubMed2004

Acute rheumatic fever: a chink in the chain that links the heart to the throat?

Acute rheumatic fever (ARF) remains a major problem in tropical regions, resource-poor countries, and minority indigenous communities. It has long been thought that group A streptococcal (GAS) pharyngitis alone was responsible for acute rheumatic fever; this belief has been supported by laboratory and epidemiological evidence gathered over more than 60 years, mainly in temperate climates where GAS skin infection is uncommon. GAS strains have been characterised as either rheumatogenic or nephritogenic based on phenotypic and genotypic properties. Primary prevention strategies and vaccine development have long been based on these concepts. The epidemiology of ARF in Aboriginal communities of central and northern Australia challenges this view with reported rates of ARF and rheumatic heart disease (RHD) that are among the highest in the world. GAS throat colonisation is uncommon, however, and symptomatic GAS pharyngitis is rare; pyoderma is the major manifestation of GAS infection. Typical rheumatogenic strains do not occur. Moreover, group C and G streptococci have been shown to exchange key virulence determinants with GAS and are more commonly isolated from the throats of Aboriginal children. We suggest that GAS pyoderma and/or non-GAS infections are driving forces behind ARF in these communities and other high-incidence settings. The question needs to be resolved as a matter of urgency because current approaches to controlling ARF/RHD in Aboriginal communities have clearly been ineffective. New understanding of the pathogenesis of ARF would have an immediate effect on primary prevention strategies and vaccine development.

Acute Disease↗
PubMed2004

Prospective study of a real-time PCR that is highly sensitive, specific, and clinically useful for diagnosis of meningococcal disease in children.

Due to the early administration of antibiotics, meningococcal disease is increasingly difficult to diagnose by culturing. Laboratory studies have shown PCR to be sensitive and specific, but there have been few clinical studies. The objectives of this study were to determine the diagnostic accuracy and clinical usefulness of meningococcal PCR through a prospective comparison of real-time PCR, nested PCR, and standard culturing of blood and cerebrospinal fluid (CSF). The setting was a tertiary-care pediatric hospital in Australia, and the participants were 118 children admitted with possible septicemia or meningitis. The main outcome measures-sensitivity, specificity, and positive and negative predictive values-were compared to a "gold standard " fulfilling clinical and laboratory criteria. For 24 cases of meningococcal disease diagnosed by the gold standard, culturing of blood or CSF was positive for 15 (63%), nested PCR was positive for 21 (88%), and real-time PCR was positive for 23 (96%). The sensitivity, specificity, and positive and negative predictive values of real-time PCR (the most sensitive test) for all specimens were, respectively, 96% (95% confidence interval, 79 to 99%), 100% (95% confidence interval, 96 to 100%), 100% (95% confidence interval, 85 to 100%), and 99% (95% confidence interval, 94 to 100%). Of 54 patients with suspected meningococcal disease at admission, 23 had positive PCR results. Only one PCR specimen was positive in a patient thought unlikely to have meningococcal disease at admission. Blood PCR remained positive for 33% of patients tested at up to 72 h. Real-time PCR has high positive and negative predictive values in this clinical setting, with better confirmation of cases than nested PCR. Targeting patients for PCR based on admission criteria appears to be practical, and the test may remain useful for several days after the start of antibiotic administration.

Adolescent↗
PubMed2004

Acute hematogenous osteomyelitis in children: recognition and management.

Acute hematogenous osteomyelitis is most common in children and has the potential to cause life-long musculoskeletal deformities. Most cases are caused by Staphylococcus aureus. Haemophilus influenzae type b (Hib) is now rare in countries that routinely use the Hib vaccine. Although magnetic resonance imaging is the preferred modality in localized disease, scintigraphy is often preferred as the first line of investigation because it helps to clarify the location of infection and exclude the presence of multifocal disease. Where the presentation is typical, there is no underlying disease, there is a low prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA), and there is a good response to antibacterial therapy, a diagnostic bone aspirate or biopsy is not necessary. The first-line antibacterial choice in most circumstances is a beta-lactamase-resistant penicillin. If CA-MRSA is suspected, the first-line options include clindamycin, the addition of an aminoglycoside or, rarely, vancomycin. In most patients, the total duration of therapy can be substantially shorter than the traditional 6 weeks, and oral therapy can be commenced after a brief course of intravenous antibacterials. We recommend 3 days of intravenous therapy followed by 3 weeks of high-dose oral antibacterials, provided there is no underlying illness, the presentation is typical and acute, and there has been a good response to treatment initially. Any deviation from this requires more intensive confirmation of the diagnosis (with imaging and/or biopsy or aspiration), and prolongation of intravenous therapy and total duration of treatment. Close monitoring and follow-up for at least 2 years are advised to detect complications.

Acute Disease↗
PubMed2004

The burden of group A streptococcal pharyngitis in Melbourne families.

BACKGROUND & OBJECTIVES: There are no recent data from industrialised countries documenting the incidence and costs of group A streptococcal (GAS) pharyngitis. Such data are important in developing policy regarding management (e.g., whether or not to use antibiotics to treat sore throat) and in planning preventive strategies, including preparing for the arrival of GAS vaccines. The present study was undertaken to estimate the incidence and costs of GAS pharyngitis in school aged children in Melbourne, Australia. We report here the results after initial 11 months of surveillance. METHODS: A total of 202 families (852 individuals) with at least one child aged 3 to 12 yr were enrolled across Melbourne in a family-based cohort study, and are being followed prospectively for 24 months. Surveillance data for acute GAS pharyngitis (including serology), throat carriage, and costs of the disease were collected. Additional cases of GAS pharyngitis have been ascertained to improve the precision of costing estimates. RESULTS: Cohort retention was 97 per cent. The spring, summer and winter carriage rates for children were 13.0, 8.0 and 16.0 per cent respectively. The incidence of GAS pharyngitis was 14 per 100 person-years for children. For every primary case there were 0.7 secondary cases and 24 per cent of families experienced at least one episode of GAS pharyngitis per year. Preliminary costing data suggest that 46 per cent of cases lead to school absenteeism and a high rate of antibiotic use. INTERPRETATION & CONCLUSION: The present data suggest that GAS pharyngitis remains very common in childhood, and that it has further implications in terms of secondary cases and costs.

Cohort Studies↗
PubMed2003

Streptococcus pyogenes recruits collagen via surface-bound fibronectin: a novel colonization and immune evasion mechanism.

This study aimed to characterize matrix assembly mechanisms on the surface of the human pathogen Streptococcus pyogenes. Among 125 S. pyogenes isolates, 61% were able to recruit collagen type IV via surface-bound fibronectin. Streptococcus gordonii expressing the fibronectin-binding repeat domain of S. pyogenes SfbI protein was equally potent in recruiting collagen, indicating that this domain was sufficient to promote fibronectin-mediated collagen recruitment. Electron microscopic analysis of streptococci revealed that fibronectin-mediated collagen recruitment led to matrix deposition on and between streptococcal cells, which induced the formation of large bacterial aggregates. Furthermore, collagen-recruiting streptococci were able to colonize collagen fibres and were protected from adhering to human polymorphonuclear cells in the presence of opsonizing antibodies. Fibronectin-mediated collagen recruitment thus represents a novel aggregation, colonization and immune evasion mechanism of S. pyogenes.

Adhesins, Bacterial↗
PubMed2002

Treatment of sore throat in light of the Cochrane verdict: is the jury still out?

There are few good-quality studies of the effectiveness of antibiotic treatment of proven group A streptococcal (GAS) pharyngitis in children; available data suggest that antibiotics may reduce symptom duration. While there is limited justification for antibiotic treatment of GAS pharyngitis to prevent acute rheumatic fever in non-Indigenous Australians, there is no justification for routine antibiotic treatment of all patients with sore throat. Two strategies are open to clinicians: not to treat GAS pharyngitis with antibiotics, in which case no investigations should be done; or to treat cases of sore throat with clinical features that suggest GAS, in which case diagnosis should be confirmed with a throat swab, and penicillin started while awaiting the result. Penicillin should be discontinued if the swab is negative, or continued for 10 days if it is positive for GAS. Surveillance of GAS infections and acute rheumatic fever is needed in Australia, as are further studies of effectiveness (including cost-effectiveness) of antibiotic treatment of proven GAS pharyngitis.

Adolescent↗