Meningococcal septicaemia has high mortality, especially when the diagnosis is delayed or missed. Early recognition is not always straightforward, as classic clinical features may be absent or overlooked at initial presentation.... more
Meningococcal septicaemia has high mortality, especially when the diagnosis is delayed or missed. Early recognition is not always straightforward, as classic clinical features may be absent or overlooked at initial presentation. Septicaemia without focal infection accounts for 15%-20% of cases of meningococcal disease and is the most worrisome manifestation in terms of diagnosis and outcome; in contrast, meningococcal meningitis is usually straightforward to diagnose, with a relatively good prognosis. Useful early clinical clues to meningococcaemia include: - a haemorrhagic (petechial or purpuric) rash; - blanching macular or maculopapular rash that appears in first 24 hours of illness; - true rigors; - severe pain in extremities, neck or back; vomiting, especially in association with headache or abdominal pain; rapid evolution of the illness; - concern of parents, relatives or friends; - patient age (highest incidence at age 3-12 months, followed by 1-4 and then 15-19 years); and -...
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Immunofluorescent antibody (IFA) testing was performed on sera drawn from 150 pregnant women in the port city of Dar es Salaam, Tanzania. Prevalence of antibodies to Rickettsia typhi was 28%, higher than in any of the 12 other African... more
Immunofluorescent antibody (IFA) testing was performed on sera drawn from 150 pregnant women in the port city of Dar es Salaam, Tanzania. Prevalence of antibodies to Rickettsia typhi was 28%, higher than in any of the 12 other African countries in which serosurveys using IFA testing have been performed. Seroprevalence of antibodies to spotted fever group rickettsiae antigens was 25.3%, comparable with that found in other sub-Saharan countries endemic for Amblyomma ticks. Only 4.7% of women were seropositive for Coxiella burnetii.
Research Interests: Adolescent, Tanzania, Pregnancy, Humans, Q Fever, and 5 moreFemale, Prevalence, Adult, immunoglobulin G, and Coxiella Burnetii
High rates of this disease are the face of Indigenous disadvantage.
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Research Interests: Microbiology, Epidemiology, Infectious Diseases, Comorbidity, Multivariate Analysis, and 17 moreBiological Sciences, Prospective studies, Humans, Female, Drug Resistance, Male, Bacteria, Staphylococcus aureus, Incidence, Risk factors, Ethnic Groups, Northern Territory, Middle Aged, Adult, Risk Factors, Seasons, and Methicillin Resistant Staphylococcus Aureus
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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... more
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.
Research Interests: Research Ethics, Informed Consent, Health Services Research, Humans, Community Based Research, and 10 moreWorking Conditions, Northern Territory, Clinical Sciences, Rheumatic Fever, Older Women, Public health systems and services research, Consumer Participation, Health Workers, Epidemiologic Studies, and Communication Service
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Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial... more
Impetigo affects more than 110 million children worldwide at any one time. The major burden of disease is in developing and tropical settings where topical antibiotics are impractical and lead to rapid emergence of antimicrobial resistance. Few trials of systemic antibiotics are available to guide management of extensive impetigo. As such, we aimed to compare short-course oral co-trimoxazole with standard treatment with intramuscular benzathine benzylpenicillin in children with impetigo in a highly endemic setting. In this randomised, controlled, non-inferiority trial, Indigenous Australian children aged 3 months to 13 years with purulent or crusted non-bullous impetigo were randomly assigned (1:1:1) to receive benzathine benzylpenicillin (weight-banded injection), twice-daily co-trimoxazole for 3 days (4 mg/kg plus 20 mg/kg per dose), or once-daily co-trimoxazole for 5 days (8 mg/kg plus 40 mg/kg per dose). At every visit, participants were randomised in blocks of six and 12, stratified by disease severity. Randomisation was done by research nurses and codes were in sealed, sequentially numbered, opaque envelopes. Independent reviewers masked to treatment allocation compared digital images of sores from days 0 and 7. The primary outcome was treatment success at day 7 in a modified intention-to-treat analysis. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000858291. Between Nov 26, 2009, and Nov 20, 2012, 508 patients were randomly assigned to receive benzathine benzylpenicillin (n=165 [156 analysed]), twice-daily co-trimoxazole for 3 days (n=175 [173 analysed]), or once-daily co-trimoxazole for 5 days (n=168 [161 analysed]). Treatment was successful in 133 (85%) children who received benzathine benzylpenicillin and 283 (85%) who received pooled co-trimoxazole (absolute difference 0·5%; 95% CI -6·2 to 7·3), showing non-inferiority of co-trimoxazole (10% margin). Results for twice-daily co-trimoxazole for 3 days and once-daily co-trimoxazole for 5 days were similar. Adverse events occurred in 54 participants, 49 (90%) of whom received benzathine benzylpenicillin. Short-course co-trimoxazole is a non-inferior, alternative treatment to benzathine benzylpenicillin for impetigo; it is palatable, pain-free, practical, and easily administered. Australian National Health and Medical Research Council.
Research Interests: Treatment Outcome, Adolescent, Humans, Child, Female, and 4 moreMale, Infant, Northern Territory, and Lancet
Abstract Like most physicians, we have developed our clinical skills by caring for patients, reading, discussing with other clinicians, and watching our mentors at work. Also, like most experienced clinicians, we rely on a relatively... more
Abstract Like most physicians, we have developed our clinical skills by caring for patients, reading, discussing with other clinicians, and watching our mentors at work. Also, like most experienced clinicians, we rely on a relatively small number of basic rules repeatedly to ...
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To date, there has been scant information about the burden of methicillin-resistant Staphylococcus aureus infections in Central Australia. Our aims were to determine the proportion of Staphylococcus aureus infections due to... more
To date, there has been scant information about the burden of methicillin-resistant Staphylococcus aureus infections in Central Australia. Our aims were to determine the proportion of Staphylococcus aureus infections due to methicillin-resistant strains in Central Australia, to characterise resistance to non-beta lactam antibiotics and to correlate fi ndings with available demographic information. We retrospectively reviewed S. aureus isolates identifi ed
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There is a high burden of disease due to group A streptococcus (GAS) in remote Northern Territory (NT) Indigenous communities. A proposed 26-valent GAS M-type vaccine covers 80-90% of pharyngeal and invasive isolates in the US. We... more
There is a high burden of disease due to group A streptococcus (GAS) in remote Northern Territory (NT) Indigenous communities. A proposed 26-valent GAS M-type vaccine covers 80-90% of pharyngeal and invasive isolates in the US. We examined the diversity and distribution of emm types in two remote Indigenous communities in the NT Top End over a 17-year period and compared them to the proposed vaccine types. Eighty emm types were identified between 1991 and 2007. Diversity in both communities was high (overall Simpson's index 0.976), but varied between communities. Prior to 2004, 71 emm types were identified and an additional 9 emm types were identified during a period of active surveillance in 2004-2005. The proposed 26-valent vaccine would be expected to cover only 20% of emm types recovered in this study. Of the 80 emm types, 16 (20%) were new sequence types identified since the last assignment of M types in 2002. The diversity of streptococcal isolates was higher than that reported from most industrialized countries, and similar to that described in several developing countries. A vaccine based on such a variable antigen is unlikely to provide effective protection in the highest risk populations.
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ABSTRACT
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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... more
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.
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Although there is extensive literature on the control of MRSA, when that concerning epidemics is excluded, only a limited amount remains regarding the control of endemic MRSA. Several guidelines have been recently published recommending... more
Although there is extensive literature on the control of MRSA, when that concerning epidemics is excluded, only a limited amount remains regarding the control of endemic MRSA. Several guidelines have been recently published recommending stringent control measures, which are often suggested based on their success in controlling MRSA outbreaks in hospitals with few MRSA or in containing MRSA cases introduced into a hospital with no MRSA. In these settings, multiple measures are usually introduced with apparently successful results. However, results may not be generalizable to other settings and we do not know the minimum effective measures required for MRSA containment. This paper aims critically to review the literature to determine whether evidence exists for the value of the infection control measures that are widely recommended in the endemic setting. Much of this literature is based on observational studies, with few randomized, controlled trials having been conducted. More well-designed studies are required before many of the principles on which we build infection control programmes can be regarded as evidence based.
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Throat swabs are regarded as the "gold... more
Throat swabs are regarded as the "gold standard" for diagnosing streptococcal pharyngitis and for surveillance research. Culturing throats in remote tropical settings is logistically difficult, and these settings are commonly burdened by high rates of streptococcal disease. The survival of streptococci on swabs may depend on whether they are of "throat" or "skin" type, as determined by emm pattern typing. The aims of this study were to compare the recovery rates of beta-hemolytic streptococci (BHS) using three different transport methods and to determine whether the recovery rates correlated with the emm pattern type. Monthly duplicate throat swabs were taken from occupants of selected households in three remote Aboriginal communities. Paired swabs were separated and handled in one of three ways: (i) direct inoculation onto culture media with cold-box transport (plated), (ii) sealed in a bag with a silica gel desiccant and cold-box transport (desiccant), and (iii) transport at ambient temperature and humidity (ambient). emm pattern typing was done by standard methods. Over 23 months, 4,842 throat swabs were taken, and 4,122 were paired. BHS were recovered on 11.5% of the 4,842 occasions (group A, 4.5%; group C, 1.7%; group G, 5.4%). Results from paired swabs showed the plated method was superior to desiccant and desiccant was better than ambient. Pooled data indicated that plated and desiccant were equivalent, and both were significantly better than ambient. There was no correlation between the emm pattern type and recovery of group A streptococci by different methods. In tropical and remote settings, cold-box transport with desiccant and subsequent inoculation of culture plates in the laboratory is a practical alternative to direct plating.
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Research Interests: Polymorphism, Australia, Public Health, Clinical Microbiology, Biological Sciences, and 14 morereal time PCR, Humans, Clinical, Staphylococcus aureus, Biological evolution, Seasonal variation, Type System, Genotype, Single Nucleotide Polymorphism, Methicillin Resistance, Soft Tissue, Methicillin Resistant Staphylococcus Aureus, Panton Valentine leukocidin, and Multilocus sequence typing
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Computed tomography (CT) was used to evaluate 15 rabbits with experimentally induced liver abscesses. The animals were examined both before and after intravenous contrast injection. After sacrificing the animals, postfreeze CT scans were... more
Computed tomography (CT) was used to evaluate 15 rabbits with experimentally induced liver abscesses. The animals were examined both before and after intravenous contrast injection. After sacrificing the animals, postfreeze CT scans were made to mark the abdomen for 1-cm thick whole body sections for correlating the gross pathology with the results of the CT scans. CT detected 15 abscesses in 13 of the 14 rabbits with true positive lesions. Ten abscesses less than 1.4 cm in diameter were not detected by CT. Contrast agent enhancement was helpful in 70% of the studies. These abscesses have characteristics similar to human liver abscesses, but there was more gas and calcium in the experimentally induced abscesses than is encountered in humans with hepatic abscesses. The model and its CT characteristics appear well suited for future studies in the diagnosis and treatment of liver abscesses.
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The aim of the study was to describe the epidemiology of pharyngitis and pyoderma in a Central Australian Aboriginal community with a high prevalence of rheumatic heart disease (RHD) and compare it to communities in the Top End of the... more
The aim of the study was to describe the epidemiology of pharyngitis and pyoderma in a Central Australian Aboriginal community with a high prevalence of rheumatic heart disease (RHD) and compare it to communities in the Top End of the Northern Territory. Following ethics approval and community consultation, selected households were enrolled and visited over a 13-month period. People were asked if they had a sore throat and/or skin sores and asked about current or recent use of antibiotics; all throats and any pyoderma lesions were swabbed for bacterial culture. Beta-haemolytic streptococci (BHS), including group A streptococcus (GAS), were identified in the central laboratory using standard methods. Household crowding was also assessed. Results were then compared to those from the Top End study. Sore throat was relatively common (480 episodes per 100 person years), although there was only one case of GAS pharyngitis in 326 consultations. Only 5.5% of children <15 years had pyoderma during the course of the study. This is the opposite picture to that reported in the Top End where symptomatic pharyngitis is rare and pyoderma is common. Although the data are limited, the epidemiology of pharyngitis and pyoderma in this Central Australian Aboriginal community appears to be more akin to that seen in temperate climates rather than tropical Top End communities. In this community, RHD preventative measure should continue to include aggressive treatment of pharyngitis according to recommendations.
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Streptococcus dysgalactiae subsp. equisimilis (groups C and G streptococci [GCS/GGS]) is an increasingly recognized human pathogen, although it may follow indirect pathways. Prospective surveillance of selected households in 3 remote... more
Streptococcus dysgalactiae subsp. equisimilis (groups C and G streptococci [GCS/GGS]) is an increasingly recognized human pathogen, although it may follow indirect pathways. Prospective surveillance of selected households in 3 remote Aboriginal communities in Australia provided 337 GCS/GGS isolates that were emm sequence-typed. Lancefield group C isolates (GCS) were localized to specific households and group G isolates (GGS) were more evenly distributed. GCS/GGS was more frequently recovered from the throat than group A streptococci (GAS [S. pyogenes]) but rarely recovered from skin sores, and then only with Staphylococcus aureus or GAS. Symptomatic GGS/GGC pharyngitis was also rare. Specific emm sequence types of GCS/GGS did not appear to cycle through the communities (sequential strain replacement) in a manner suggesting acquisition of type-specific immunity. These communities already have high levels of streptococcal and poststreptococcal disease. GCS/GGS may increase in importance as it acquires key virulence factors from GAS by lateral gene transfer.
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Research Interests: Australia, Humans, Bacterial Toxins, Clinical, Bacteria, and 13 moreStaphylococcus aureus, Clinical microbiology and infection control, Fusion, Clinical Sciences, High Resolution, Anti-Bacterial Agents, Genotype, Melting, Reproducibility of Results, Microbial Sensitivity Tests, Genetic variation, Methicillin Resistant Staphylococcus Aureus, and Transition Temperature
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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... more
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. 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. 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. 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.
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To assess specific performance indicators relating to a register-based acute rheumatic fever and rheumatic heart disease (ARF/RHD) prevention program in a remote Australian Aboriginal community in order to identify the most appropriate... more
To assess specific performance indicators relating to a register-based acute rheumatic fever and rheumatic heart disease (ARF/RHD) prevention program in a remote Australian Aboriginal community in order to identify the most appropriate avenues for improvements in delivery of services. Information kept on the central ARF/RHD register was compared with an amalgamated dataset from three other sources. The community clinic charts of identified patients were reviewed for information regarding accuracy of diagnosis and the number of doses of benzathine penicillin received in the last year. Specific follow-up arrangements were assessed and compared with practice guidelines. The central ARF/RHD register contained the names of 58 of the 72 (81%) people identified in the community as eligible for inclusion. Only 42% (22/52) of people receiving antibiotic prophylaxis had received 80% or more of the recommended doses in the previous year; service delivery was significantly better for females than males (p = 0.004). Individuals in priority category 1 (most severe disease) were found to be receiving follow-up and investigation according to guidelines. About half the people in categories 2 (moderate disease) and 3 (mild disease) had been inadequately investigated and/or missed out on follow-up appointments. The ARF/RHD prevention program in this large remote Aboriginal community is struggling to deliver services to a substantial proportion of people who require them. Specific interventions, especially those related to men's health, may be required to correct the problems.
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This study was carried out to determine if single-dose antimicrobial prophylaxis is sufficient for cardiac surgery. The study was a prospective non-randomized trial of 353 consecutive patients undergoing cardiac surgery. Group A (n = 151)... more
This study was carried out to determine if single-dose antimicrobial prophylaxis is sufficient for cardiac surgery. The study was a prospective non-randomized trial of 353 consecutive patients undergoing cardiac surgery. Group A (n = 151) received 48 h of prophylaxis and Group B (n = 202) received a single dose. Cephazolin was used in all patients except those at high risk from methicillin-resistant Staphylococcus aureus (MRSA) who received teicoplanin and timentin. There was an overall in-hospital infection rate of 2.8%. There was no significant difference in rate or type of infection between the two groups. An in-hospital infection rate of 2.8% compares favourably with other reported series. Single-dose antimicrobial prophylaxis is as effective as a 48-h regimen. Targeting high-risk groups is effective.
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ABSTRACT In developing countries, Isospora belli and Cyclospora cayetanensis frequently cause chronic diarrhea in HIV-infected patients. To compare 1 week of trimethoprim-sulfamethoxazole treatment and 1 week of ciprofloxacin treatment in... more
ABSTRACT In developing countries, Isospora belli and Cyclospora cayetanensis frequently cause chronic diarrhea in HIV-infected patients. To compare 1 week of trimethoprim-sulfamethoxazole treatment and 1 week of ciprofloxacin treatment in HIV-infected patients with chronic diarrhea caused by I. belli and C. cayetanensis. Randomized, controlled trial. HIV clinic in Port-au-Prince, Haiti. 42 HIV-infected patients with chronic diarrhea due to I. belli (n = 22) or C cayetanensis (n = 20). Patients were randomly assigned to receive oral trimethoprim-sulfamethoxazole (160 mg or 800 mg) or ciprofloxacin (500 mg) twice daily for 7 days. Patients who responded clinically and microbiologically received prophylaxis for 10 weeks (1 tablet orally, three times per week). Treatment success was measured by cessation of diarrhea and negative stool examination at day 7. Prophylaxis success was measured by recurrent disease rate. Diarrhea ceased in all 19 patients treated with trimethoprim-sulfamethoxazole. Eighteen of 19 patients had negative results on stool examination at day 7 (95%). Among the 23 patients who received ciprofloxacin, diarrhea ceased in 20 (87% [CI; 66% to 97%]) and 16 had negative results on stool examination at day 7 (70%). By survival analysis, diarrhea from isosporiasis and cyclosporiasis ceased more rapidly with trimethoprim-sulfamethoxazole than with ciprofloxacin. All patients receiving secondary prophylaxis with trimethoprim-sulfamethoxazole remained disease-free, and 15 of 16 patients receiving secondary prophylaxis with ciprofloxacin remained disease-free. A 1-week course of trimethoprim-sulfamethoxazole is effective in HIV-infected patients with cyclosporiasis or isosporiasis. Although ciprofloxacin is not as effective, it is acceptable for patients who cannot tolerate trimethoprim-sulfamethoxazole.