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Biomedical subjects

J R Carapetis

Publications and source records attributed to J R Carapetis.

At least 19 recordsLinked to original sources

As a bacterial culture medium, citrated sheep blood agar is a practical alternative to citrated human blood agar in laboratories of developing countries.

Human blood agar (HuBA) is widely used in developing countries for the isolation of bacteria from clinical specimens. This study compared citrated sheep blood agar (CSBA) and HuBA with defibrinated horse blood agar and defibrinated sheep blood agar (DSBA) for the isolation and antibiotic susceptibility testing of reference and clinical strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Reference and clinical strains of all organisms were diluted in brain heart infusion and a clinical specimen of cerebrospinal fluid and cultured on all agars. Viable counts, colony morphology, and colony size were recorded. Susceptibility testing for S. pneumoniae and S. pyogenes was performed on defibrinated sheep blood Mueller-Hinton agar, citrated sheep blood Mueller-Hinton agar (CSB MHA), and human blood Mueller-Hinton agar plates. For all organisms, the colony numbers were similar on all agars. Substantially smaller colony sizes and absent or minimal hemolysis were noted on HuBA for all organisms. Antibiotic susceptibility results for S. pneumoniae were similar for the two sheep blood agars; however, larger zone sizes were displayed on HuBA, and quality control for the reference strain failed on HuBA. For S. pyogenes, larger zone sizes were demonstrated on HuBA and CSBA than on DSBA. Poor hemolysis made interpretation of the zone sizes difficult on HuBA. CSBA is an acceptable alternative for the isolation of these organisms. The characteristic morphology is not evident, and hemolysis is poor on HuBA; and so HuBA is not recommended for use for the isolation or the susceptibility testing of any of these organisms. CSB MHA may be suitable for use for the susceptibility testing of S. pneumoniae.

Agar↗

Pneumococcal nasopharyngeal carriage and patterns of penicillin resistance in young children in Fiji.

BACKGROUND: Little is known about nasopharyngeal carriage and the patterns of antibiotic resistance of pneumococci in Pacific nations. We set out to document pneumococcal nasopharyngeal carriage and associated risk factors, antimicrobial resistance and serotypes in healthy children in Fiji. METHODS: A cross-sectional survey of healthy children aged 3-13 months was conducted. Nasopharyngeal (NP) swabs were collected from each child and processed according to standard methods. Antimicrobial resistance was determined by disk diffusion and confirmed by E-testing. Serotyping was performed by the Quellung reaction. RESULTS: Of 440 consecutive NP swabs taken, 195 were S. pneumoniae-positive (carriage rate 44.3%). Higher rates were found in the indigenous Fijian population. Penicillin non-susceptibility was found in 11.4% of isolates, with one isolate demonstrating high-level resistance. Cotrimoxazole resistance was common (20.3%) and no isolates were chloramphenicol-resistant. Multi-drug resistance was uncommon. The commonest serotypes were 6A (13.2%), 23F (8.3%), 19F (7.4%) and 6B (6.2%). Thirty per cent were included in the 7-valent pneumococcal conjugate vaccine (PCV), 54.3% if cross-reacting strains were included. Being indigenous Fijian or having symptoms of acute respiratory infection were independent risk factors for carriage. CONCLUSIONS: Pneumococcal NP carriage is common in Fijian children. Penicillin resistance has been documented for the first time in Fiji and, as a result, first-line treatment for meningitis has been altered. Being indigenous Fijian is a risk factor for disease, although the reasons for this are unclear. A low proportion of carriage serotypes are covered by the existing 7-valent PCV.

Carrier State↗

Chest X-ray-confirmed pneumonia in children in Fiji.

OBJECTIVE: To calculate the incidence and document the clinical features of chest X-ray- (CXR-) confirmed pneumonia in children aged between 1 month and 5 years living in Greater Suva, Fiji. METHODS: A retrospective review was undertaken of children aged between 1 month and 5 years with a discharge diagnosis suggesting a lower respiratory tract infection (LRTI) admitted to the Colonial War Memorial Hospital in Suva, Fiji, in the first 10 days of each month from 1 January 2001 to 31 December 2002. Clinical data were collected and CXRs were reread and classified according to WHO standardized criteria for CXR-confirmed pneumonia. FINDINGS: Two hundred and forty-eight children with LRTI met the inclusion criteria. CXRs were obtained for 174 (70%) of these cases, of which 59 (34%) had CXR-confirmed pneumonia. The annual incidence of CXR-confirmed pneumonia was 428 cases per 100,000 children aged between 1 month and 5 years living in Greater Suva. If a similar proportion of the children for whom CXRs were unavailable were assumed to have CXR-confirmed pneumonia, the incidence was 607 per 100,000. The incidence appeared to be higher in Melanesian Fijian than Indo-Fijian children. The case-fatality rate was 2.8% in all children with LRTI, and 6.8% in those with CXR-confirmed pneumonia. CONCLUSION: This is the first study to document the incidence of CXR-confirmed pneumonia in a Pacific Island country, and demonstrates a high incidence. A significant proportion of hospital admissions of children with LRTI are likely to be preventable by the introduction of pneumococcal conjugate vaccine.

Benchmarking↗

New normal ranges of antistreptolysin O and antideoxyribonuclease B titres for Australian children.

OBJECTIVE: To determine age-specific upper limit of normal (ULN) values of the ASO and ADB titres in children aged 4-14 years in urban Melbourne. Serology is often used to diagnose a preceding Streptococcus pyogenes infection, particularly in potential cases of rheumatic fever and post-streptococcal glomerulonephritis. The most commonly used antigens are antistreptolysin O (ASO) and antideoxyribonuclease B (ADB). Reference ranges used in Australia for these serological markers are usually based on data in adults from other countries. There are no age-specific reference values for Australian children. METHODS: Sixty-six sera from children with no history of recent streptococcal infection were obtained in May-June 2002. The children were divided into three age groups for analysis: 4-5 (n = 20), 6-9 (n = 19) and 10-14 (n = 25) years. The geometric mean titre and ULN (defined as the 80th percentile) for the ASO and ADB titres for each age group were determined in both international and log units. RESULTS: The ULN for ASO titres in each age group was 120 (2.08 log units), 480 (2.68) and 320 (2.51). The ULN for ADB titres in each age group was 100 (2.00 log units), 400 (2.60) and 380 (2.58). CONCLUSION: The ASO and ADB ULN values in school-aged children are higher than the current reference ranges suggest.

Adolescent↗

A pilot study of the quality of informed consent materials for Aboriginal participants in clinical trials.

OBJECTIVE: To pilot informed consent materials developed for Aboriginal parents in a vaccine trial, and evaluate their design and the informed consent process. METHODS: Cross sectional quantitative and qualitative survey of 20 Aboriginal and 20 non-Aboriginal women in Alice Springs. Information about the proposed research was presented to Aboriginal participants by an Aboriginal researcher, using purpose designed verbal, visual, and written materials. Non-Aboriginal participants received standard materials developed by the sponsor. Questionnaires were used to evaluate recall and understanding immediately and five days later. Qualitative analysis of Aboriginal participants' interviews was performed. RESULTS: There were no differences between the groups in understanding of diseases prevented by the vaccine, the potential risks of participating, or the voluntary nature of participation. Most Aboriginal participants had difficulty with the concept of a "licensed" versus "unlicensed" vaccine. The non-Aboriginal group had a good understanding of this. Aboriginal participants identified the use of the flipchart, along with a presentation by a doctor and Aboriginal health worker, as preferred delivery modes. Group presentations were preferred rather than one-on-one discussions. The use of the questionnaire posed considerable methodological difficulties. CONCLUSIONS: A one-off oral presentation to Aboriginal participants is unlikely to produce "informed consent". Key but unfamiliar concepts require identification and particularly considered presentation.

Clinical Trials as Topic↗

High incidence of Haemophilus influenzae type b infection in children in Pacific island countries.

The Haemophilus influenzae type b (Hib) disease burden among children <5 years old in 4 Pacific island countries (PICs) was estimated. The incidence of confirmed Hib meningitis was calculated using the numbers of culture-confirmed isolates. In addition, the World Health Organization (WHO) Hib Rapid Assessment Tool (RAT) was used to estimate the true Hib meningitis incidence and the number of Hib meningitis and pneumonia cases, as well as the number of deaths due to Hib meningitis and pneumonia. The Hib meningitis annual incidence in 3 PICs was 70-84 cases per 100,000 children <5 years old. For PICs, the RAT is likely to overestimate the Hib pneumonia burden, as it assumes a 5 : 1 ratio of Hib pneumonia to Hib meningitis. The true ratio is likely to be 1 : 1. The high Hib disease burden and the relative cost-effectiveness of Hib vaccine make the introduction of Hib vaccine a good investment for PICs, costing US1000 dollars-US10,000 dollars for each death prevented--a number that ignores savings from reductions in the cost of treatment.

Bacterial Capsules↗

Screening for intestinal parasites in recently arrived children from East Africa.

BACKGROUND: Intestinal parasitic carriage is common in East African populations with a wide spectrum of clinical severity. There are scant data on the rates of carriage in East African immigrants to Australia. This study describes the prevalence of and risk factors for intestinal parasite carriage among children recently arrived from East African countries. METHODS: Children aged 0-17 years, who attended an outpatient clinic, were born in East Africa and had immigrated since 1998 were eligible to participate. A single preserved stool specimen was collected for faecal microscopy, and blood tests were conducted for Strongyloides and Schistosoma serology, full blood examination and serum ferritin. RESULTS: One hundred and thirty-five children (median age 8.1 years, range 1.0-17.5) participated, of whom 133 (99%) provided a stool specimen. Parasites were detected in 50% of samples, and 18% of children carried a possibly pathogenic species. No child was symptomatic at diagnosis. Positive or equivocal serology occurred in 11% of children for Strongyloides and 2% for Schistosoma. Anaemia and iron deficiency were detected in 16% of all children. Those carrying an intestinal parasite were older (mean age 9.8 vs 7.4 years, P= 0.002) and less likely to be anaemic (odds ratio 0.37, 95% confidence interval 0.14-0.96) than those who were not carriers. CONCLUSIONS: Carriage of intestinal parasites is common among children from East Africa. Those carrying pathogenic organisms require treatment and follow up to ensure eradication. The results of this survey support the need for routine assessment of newly arrived immigrants from East Africa for intestinal parasites, anaemia and iron deficiency.

Adolescent↗

Duration of antibiotics in children with osteomyelitis and septic arthritis.

OBJECTIVE: To evaluate the outcomes of children with acute osteomyelitis and septic arthritis at a hospital where short-duration antibiotic treatment (< or = 3.5 weeks) was considered routine. METHODOLOGY: We carried out a retrospective chart review, with telephone interviews to follow up and determine long-term outcomes. Patients were selected to be at low risk for complications (illness < or = 14 days, no underlying disease, uncomplicated presentation). RESULTS: Thirty-two children with osteomyelitis (OM), 34 with septic arthritis (SA) and five with OM and SA (OMSA) were included. Blood cultures were positive (mainly Staphylococcus aureus) in 15% of patients who had not had prior antibiotic treatment, and microbiological confirmation (positive blood culture, Gram stain or culture of surgical specimen) was obtained in 36%. The median duration of antibiotic treatment was 5.4, 4.4 and 5.0 weeks for OM, SA and OMSA, respectively. Only 22% of patients received antibiotics for 3.5 weeks or less. Overall, the recurrence rate was 1.4%. At follow-up, only two patients had mild occasional pain at the site of the original infection; all patients had normal function. CONCLUSIONS: Contrary to expectations and local protocols, most patients were treated with conventional long-duration therapy. Patients treated for short courses had good outcomes. The low rate of complications may make randomized controlled equivalence trials unfeasible. Increasing evidence of the efficacy and safety of short-duration treatment (3-3.5 weeks) for acute, uncomplicated OM or SA in children suggests that this could be accepted as the standard treatment. However, this should be evaluated prospectively using a register, with at least 12 months' of follow-up.

Acute Disease↗

Childhood invasive pneumococcal disease in Tasmania, 1994-2000.

OBJECTIVE: To describe the burden of invasive pneumococcal disease in Tasmanian children, including age-specific incidence and antibiotic-resistance pattern. METHODS: A population-based retrospective study was carried out, examining cases of childhood disease associated with isolates of Streptococcus pneumoniae from normally sterile sites, identified via scrutiny of laboratory records at all major Tasmanian laboratories during a 7-year period between January 1994 and December 2000. Medical records were sub-sequently examined for information describing the clinical syndrome and course of disease. RESULTS: Invasive pneumococcal disease was identified in 76 children during the 7-year period. The incidence per 100 000 children was 28.5 (95% CI 22.0-36.3) in children under 5 years and 54.3 (95% CI 40.2-71.8) in children under 2 years. The incidence of meningitis in children younger than 2 years was 12.2 (95% CI 6.1-21.8). Penicillin resistance was observed in 2.6% of cases, with no high level resistance. Predisposing conditions were identified in 34% of children with invasive disease. CONCLUSIONS: The incidence of invasive pneumococcal disease was comparable to many urban populations in Australia. The high rate of predisposing conditions supports the recommendations of the Australian Technical Advisory Group on Immunisation for targeted immunization in this group. The paucity of data describing Indigenous status is an argument for improved data collection in this area. The low level of penicillin resistance necessitates ongoing surveillance, and the lack of serotype information requires prospective data collection.

Adolescent↗

Systematic review of rheumatic heart disease prevalence in children in developing countries: the role of environmental factors.

OBJECTIVES: To consider the worldwide prevalence of rheumatic heart disease in children in developing countries using surveys with uniform methodologies, and to consider the effect of environmental factors including socio-economic status, overcrowding, urbanization, nutrition and access to medical services on the distribution of rheumatic heart disease in developing countries. METHODS: Sixty-one surveys of the prevalence of rheumatic heart disease in developing countries were found using a systematic review of MEDLINE from January 1976 to July 1999. Twenty-four studies were selected for comparison based on their uniform methodological and diagnostic techniques. RESULTS: There is a high prevalence of rheumatic heart disease in the Pacific region with a lower prevalence in the Indian subcontinent, Asian, sub-Saharan African, Mediterranean, Latin American and Caribbean regions. However, aside from the Indian subcontinent, these regions have not been well studied, and it may be that the true prevalence is actually higher. CONCLUSIONS: There is a lack of good quality prevalence surveys of rheumatic heart disease in developing countries. It appears that a threshold level where higher socio-economic status is associated with reduced prevalence of rheumatic heart disease is not reached in developing countries. Therefore, differences in prevalence between socio-economic groups in the one area cannot be detected. A similar case can be made for overcrowding. Many regions need well-designed studies of rheumatic heart disease that incorporate assessment of environmental factors as well as the study of the microbiological epidemiology of rheumatic heart disease and group A streptococci.

Acute Disease↗

Randomized, controlled trial comparing once daily and three times daily gentamicin in children with urinary tract infections.

OBJECTIVE: To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily (OD) gentamicin dosing in children with severe urinary tract infections (UTI). METHODS: An open, randomized, controlled trial comparing OD with three times daily (TD) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI. Daily doses (milligrams per kg per day) of gentamicin in both groups were 7.5 (<5 years old), 6.0 (5 to 10 years old) and 4.5 (>10 years old). RESULTS: There were 179 children enrolled (90 OD, 89 TD). Baseline clinical characteristics and pathogens were similar, except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group. Median gentamicin treatment durations were 3.0 (OD) and 2.7 (TD) days. Mean peak gentamicin concentrations were 17.3 (OD) vs. 6.4 (TD) mg/l; 99% of peak concentrations were >7 mg/l in the OD group whereas 16% of peak concentrations were <5 mg/l in the TD group. Mean trough concentrations were 0.35 (OD) vs. 0.55 (TD) mg/l. In the OD group 4% of trough concentrations were > or = 2 mg/l, whereas in the TD group only 0.7% were > or = 2 mg/l. Age or prior elevated peak concentrations did not predict high trough concentrations. Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination. There were no clinical or bacteriologic failures. The two disease-related complications were confined to the OD group. No nephro- or ototoxicity was identified. CONCLUSIONS: With age-appropriate dosing and measurement of serum trough concentrations before the second dose, OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years.

Anti-Bacterial Agents↗

Rheumatic fever in a high incidence population: the importance of monoarthritis and low grade fever.

AIMS: To describe the clinical features of rheumatic fever and to assess the Jones criteria in a population and setting similar to that in many developing countries. METHODS: The charts of 555 cases of confirmed acute rheumatic fever in 367 patients (97% Aboriginal) and more than 200 possible rheumatic fever cases from the tropical "Top End" of Australia's Northern Territory were reviewed retrospectively. RESULTS: Most clinical features were similar to classic descriptions. However, monoarthritis occurred in 17% of confirmed non-chorea cases and 35% of unconfirmed cases, including up to 27 in whom the diagnosis was missed because monoarthritis is not a major manifestation. Only 71% and 25% of confirmed non-chorea cases would have had fever using cut off values of 38 degrees C and 39 degrees C, respectively. In 17% of confirmed non-chorea cases, anti-DNase B titres were raised but antistreptolysin O titres were normal. Although features of recurrences tended to correlate with initial episodes, there were numerous exceptions. CONCLUSIONS: Monoarthritis and low grade fever are important manifestations of rheumatic fever in this population. Streptococcal serology results may support a possible role for pyoderma in rheumatic fever pathogenesis. When recurrences of rheumatic fever are common, the absence of carditis at the first episode does not reliably predict the absence of carditis with recurrences.

Adolescent↗

Contrasting molecular epidemiology of group A streptococci causing tropical and nontropical infections of the skin and throat.

Disease caused by group A streptococci (GAS) in tropical regions often takes the form of impetigo, whereas pharyngitis tends to predominate in temperate zones. GAS derived from asymptomatic throat infections and pyoderma lesions of rural Aboriginal Australians were evaluated for phylogenetic distant emm genes, which represent ecological markers for tissue site preference. On the basis of the percentage of total isolates from a given tissue, emm pattern A-C organisms exhibited a stronger predilection for the throat, whereas pattern D organisms preferred the skin. Only 16% of isolates collected by active surveillance displayed pattern A-C, which reflects the low incidence of oropharyngeal infection. Importantly, most (70%) pattern A-C organisms were isolated from skin sores, despite their innate tendency to infect the throat. Combined with findings from nontropical populations, analysis of the data supports the hypothesis that GAS tissue preferences are genetically predetermined and that host risk factors for infection strongly influence the differential reproduction of individual clones.

Adult↗

Cumulative incidence of rheumatic fever in an endemic region: a guide to the susceptibility of the population?

Aboriginal Australians in northern Australia are subject to endemic infection with group A streptococci, with correspondingly high rates of acute rheumatic fever and rheumatic heart disease. For 12 communities with good ascertainment, the estimated lifetime cumulative incidence of acute rheumatic fever was approximately 5.7%, whereas over the whole population, with less adequate ascertainment, the cumulative incidence was only 2.7%. The corresponding prevalences of established rheumatic heart disease were substantially less than the cumulative incidences of acute rheumatic fever, at least in part because of poor ascertainment. The cumulative incidence of acute rheumatic fever estimates the proportion of susceptible individuals in endemically exposed populations. Our figures of 2.7-5.7% susceptible are consistent with others in the literature. Such comparisons suggest that the major part of the variation in rheumatic fever incidence between populations is due to differences in streptococcal exposure and treatment, rather than to any difference in (genetic) susceptibility.

Acute Disease↗

Skin infections and infestations in Aboriginal communities in northern Australia.

The most important skin infections in Aboriginal communities in central and northern Australia are scabies and streptococcal pyoderma. Scabies is endemic in many remote Aboriginal communities, with prevalences in children up to 50%. The cycles of scabies transmission underlie much of the pyoderma. Up to 70% of children have skin sores, with group A streptococcus (GAS) the major pathogen. Group A streptococcus is responsible for the continuing outbreaks of post-streptococcal glomerulonephritis and acute rheumatic fever (ARF). The cycles of scabies transmission in dogs and humans do not appear to significantly overlap. Guidelines have been developed for community control of scabies and skin sores and successful community initiated coordinated programmes have occurred. The anthropophilic dermatophyte Trichophyton rubrum is ubiquitous in many communities, again reflecting living conditions. Other skin infections related to the tropical environment include melioidosis, nocardiosis, Chromobacterium violaceum and chromoblastomycosis. Sustainable and long-term improvements in scabies, skin sores and GAS-related disease and tinea require fundamental changes that address social and economic inequities and, in particular, living conditions and overcrowding.

Adult↗

Clinical and epidemiological features of group A streptococcal bacteraemia in a region with hyperendemic superficial streptococcal infection.

Reports of increasing incidence and severity of invasive group A streptococcal (GAS) infections come mainly from affluent populations where exposure to GAS is relatively infrequent. We conducted a 6-year retrospective review of GAS bacteraemia in the Northern Territory of Australia, comparing the Aboriginal population (24% of the study population), who have high rates of other streptococcal infections and sequelae, to the non-Aboriginal population. Of 72 episodes, 44 (61%) were in Aboriginal patients. All 12 cases in children were Aboriginal. Risk factors were implicated in 82% of episodes (91% in adults) and there was no significant difference in the proportion of Aboriginal compared to non-Aboriginal patients with at least one risk factor. Genetic typing of isolates revealed no dominant strains and no evidence of a clone which has been a common cause of these infections elsewhere.

Adolescent↗