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Bart J Currie

Publications and source records attributed to Bart J Currie.

At least 19 recordsLinked to original sources

Invasive Streptococcus dysgalactiae subspecies equisimilis compared with Streptococcus pyogenes in Australia, 2011-23, and the emergence of a multi-continent stG62647 lineage: a retrospective clinical and genomic epidemiology study.

BACKGROUND: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is closely related to Streptococcus pyogenes, with overlapping disease manifestations. We compared the clinical and genomic epidemiology of invasive SDSE with invasive S pyogenes across different settings in Australia and phylogenetically contextualised the SDSE sequences within a global cohort of genomes. METHODS: In this retrospective clinical and genomic epidemiology study, cases of invasive SDSE isolated from normally sterile sites were identified and whole-genome sequenced across five hospital networks in temperate southeast Australia (Melbourne and Sydney) and the tropical Top End of the Northern Territory. SDSE disease incidence, case demographics, clinical outcomes, and longitudinal lineage dynamics were compared between southeast Australia and the Top End and to co-collected invasive S pyogenes cases in each region. SDSE genomes and lineages were also contextualised within 1166 global SDSE sequences. Genomic transmission clusters (not necessarily direct transmission) were inferred between isolates from different individuals by single-linkage clustering at a single nucleotide polymorphism threshold of less than or equal to seven for SDSE and less than or equal to five for S pyogenes based on previous transmission analyses. FINDINGS: Between Jan 1, 2011, and Feb 28, 2023, there were 693 invasive SDSE cases and 995 invasive S pyogenes cases. Invasive SDSE occurred almost exclusively in adults. The overall invasive SDSE incidence in southeast Australia was similar to invasive S pyogenes (incidence rate ratio [IRR] 1&#xb7;15, 95% CI 0&#xb7;91-1&#xb7;46; p=0&#xb7;26) and increased over the study period (IRR 1&#xb7;06 per year, 95% CI 1&#xb7;05-1&#xb7;08; p<0&#xb7;0001) from 1&#xb7;30 cases per 10&#x2009;000 admissions in 2011 to 3&#xb7;72 cases per 10&#x2009;000 admissions in the first 2 months of 2023 (95% CI 2&#xb7;13-6&#xb7;07). In southeast Australia, where stringent COVID-19 non-pharmaceutical interventions (NPIs) were implemented between 2020 and 2021, the SDSE incidence plateaued during 2020-21 but did not significantly decline (IRR 1&#xb7;09 compared with 2017-19, 95% CI 0&#xb7;88-1&#xb7;35; p=0&#xb7;47). By contrast, S pyogenes incidence substantially declined in 2020-21 in southeast Australia (IRR 0&#xb7;35 compared to 2017-19, 95% CI 0&#xb7;22-0&#xb7;52; p=0&#xb7;017). In the Top End, SDSE incidence was lower than S pyogenes (IRR 0&#xb7;24, 95% CI 0&#xb7;19-0&#xb7;31; p<0&#xb7;0001). However, crude incidence remained higher than southeast Australia (crude IRR 1&#xb7;24, 95% CI 1&#xb7;07-1&#xb7;42; p=0&#xb7;0037) and disproportionately affected First Nations Australians in the Top End compared with non-First Nations individuals (IRR 3&#xb7;36, 95% CI 2&#xb7;33-4&#xb7;85; p<0&#xb7;0001). Comparing 2020-21 with 2017-19, there was no decline in SDSE (IRR 1&#xb7;27, 95% CI 0&#xb7;73-2&#xb7;24; p=0&#xb7;45) or S pyogenes (IRR 0&#xb7;97, 95% CI 0&#xb7;80-1&#xb7;18; p=0&#xb7;81) incidence in the Top End, which did not implement prolonged stringent COVID-19 NPIs. Analysing the available genomes of invasive cases and in lineages for which more than or equal to five invasive cases occurred, only 24 (6%) of 384 SDSE cases were assigned to genomic transmission clusters, compared with 271 (52%) of 524 S pyogenes cases. An stG62647 lineage encompassed 113 (26%) of 436 sequenced SDSE genomes. Analysis of available SDSE sequences from Australia, western Europe, and North America inferred concurrent international expansion of the stG62647 lineage in all three regions between 1990 and 2005. INTERPRETATION: We identified a substantial burden of invasive SDSE, dominated by the emergent stG62647 lineage. The contrasting epidemiology between species in the different Australian regions, during COVID-19 NPIs, and genomic infection patterns indicates transmission dynamic, pathogen population, and host-pathogen interaction differences between SDSE and S pyogenes and indicates implications for disease control measures. FUNDING: Australian National Health and Medical Research Council.

Humans↗

Diagnostic and phylogenetic perspectives of the 2023 Murray Valley encephalitis virus outbreak in Australia: an observational study.

BACKGROUND: An outbreak of Murray Valley encephalitis virus (MVEV), the largest since 1974, was observed in Australia between Jan 1 and July 31, 2023. This study aims to characterise the utility of diagnostic platforms, testing algorithms, and genomic characteristics of MVEV to facilitate a comprehensive framework for MVEV testing and surveillance in the outbreak setting. METHODS: In this observational study, we assessed flavivirus diagnostics for all patients with suspected Murray Valley encephalitis in Australia from Jan 1 to July 31, 2023. We included all patients with confirmed Murray Valley encephalitis, probable Murray Valley encephalitis, or acute unspecified flavivirus infection using the Communicable Diseases Network Australia case definition. Cases were excluded if an alternative diagnosis was identified. We collected blood, serum, cerebrospinal fluid, brain tissue, urine, or a combination of these samples, as appropriate and at the discretion of the treating clinician. We conducted multimodal diagnostic testing, which included flavivirus-specific serological and nucleic acid amplification testing. Metagenomic next-generation sequencing, including next-generation deep sequencing, target-enrichment, and targeted amplification, was conducted on human and representative mosquito-derived samples obtained from established mosquito population surveillance programmes for phylogenetic analysis. FINDINGS: 27 patients with encephalitis were assessed for MVEV between Jan 1, 2023, and July 31, 2023, 23 (85%) of whom fulfilled national case definitions for confirmed Murray Valley encephalitis. Patient ages ranged from 6 weeks to 83 years (median 62&#xb7;0 years [IQR 31&#xb7;0-67&#xb7;5]) and patients were mostly male (21 [78%] male patients and six [22%] female patients). Incidence varied widely by geographical region and was highest in the Northern Territory (32&#xb7;0 per 1&#x2009;000&#x2009;000 population). Diagnostic specimen collection generally occurred promptly (median 6&#xb7;0 days [IQR 4&#xb7;0-14&#xb7;5] from symptom onset to diagnostic specimen collection). In seven patients, case assignation relied on convalescent serum samples to assess for seroconversion or an appropriate rise in antibody titre (to four times the initial value or greater), or both. MVEV-specific IgM was detectable in serum samples of 17 (81%) of 21 patients tested by day 7 and MVEV IgG or total antibody (TAb) were detected in 18 (100%) of 18 patients tested by day 30. MVEV-specific IgM (or TAb) and MVEV RNA were detected in cerebrospinal fluid collected within 14 days of symptom onset in nine (39%) of 23 patients and seven (28%) of 25 patients, respectively. Phylogenetic analysis revealed two circulating MVEV genotypes, G1A and G2, in mosquitoes and humans in 2023. In southeast Australia, only G1A was detected and probably introduced from enzootic foci in northern Australia. INTERPRETATION: This study provides a comprehensive overview of the diagnostic workflows and phylogenetic evaluations used during the 2023 MVEV outbreak in Australia, emphasising the importance of a multimodal approach for accurate and timely confirmation of flavivirus infection. Further One Health surveillance for MVEV and other zoonotic flaviviruses is key, given potential expanded ecological niches in the context of episodic climatic events. FUNDING: None.

Humans↗

Temporal and geographical lineage dynamics of invasive Streptococcus pyogenes in Australia from 2011 to 2023: a retrospective, multicentre, clinical and genomic epidemiology study.

BACKGROUND: Defining the temporal dynamics of invasive Streptococcus pyogenes (group A Streptococcus) and differences between hyperendemic and lower-incidence regions provides crucial insights into pathogen evolution and, in turn, informs preventive measures. We aimed to examine the clinical and temporal lineage dynamics of S pyogenes across different disease settings in Australia to improve understanding of drivers of pathogen diversity. METHODS: In this retrospective, multicentre, clinical and genomic epidemiology study, we identified cases of invasive S pyogenes infection from normally sterile sites between Jan 1, 2011, and Feb 28, 2023. Data were collected from five hospital networks across low-incidence regions in temperate southeast Australia and the hyperendemic, tropical, and largely remote Top End of the Northern Territory of Australia. The crude incidence rate ratio (IRR) of bloodstream S pyogenes infection comparing the Top End and southeast Australia and in First Nations people compared with non-First Nations people was estimated by quasi-Poisson regression. We estimated odds ratios (ORs) of intensive care unit (ICU) admission, in-hospital mortality, and 30-day mortality for the Top End versus southeast Australia using logistic regression. Retrieved and successfully sequenced isolates were assigned lineages at whole-genome resolution. Temporal trends in the composition of co-circulating lineages were compared between the two regions. We used an S&#x2009;pyogenes-specific multistrain simulated transmission model to examine the relationship between host population-specific parameters and observed pathogen lineage dynamics. The prevalence of accessory genes (those present in 5-95% of all genomes) was compared across geographies and temporal periods to investigate genomic drivers of diversity. FINDINGS: We identified 500 cases of invasive S pyogenes infection in patients in the Top End and 495 cases in patients in southeast Australia. The crude IRR of bloodstream infection for the Top End compared with southeast Australia was 5&#xb7;97 (95% CI 4&#xb7;61-7&#xb7;73) across the entire study period; in the Top End, infection disproportionately affected First Nations people compared with non-First Nations people (5&#xb7;41, 4&#xb7;28-6&#xb7;89). The odds of in-hospital mortality (OR 0&#xb7;43, 95% CI 0&#xb7;26-0&#xb7;70), 30-day mortality (0&#xb7;38, 0&#xb7;23-0&#xb7;63), and ICU admission (0&#xb7;42, 0&#xb7;30-0&#xb7;59) were lower in the Top End than in southeast Australia. Longitudinal lineage analysis of 642 S pyogenes genomes identified waves of replacement with distinct lineages in the Top End, whereas southeast Australia had a small number of dominant lineages that persisted and cycled in frequency. The transmission model qualitatively reproduced a similar pattern of replacement with distinct lineages when using a high transmission rate, small population size, and high levels of human movement-characteristics similar to those of communities in the hyperendemic Top End. Using a lower transmission rate, larger population size, and lower levels of migration similar to those of communities in urbanised southeast Australia, the transmission model qualitatively reproduced a pattern of dominant lineages that cycled in frequency. Despite distinct circulating lineages, the prevalence of accessory genes in the bacterial population was maintained across geographies and temporal periods. INTERPRETATION: In a hyperendemic setting, the replacement of distinct S pyogenes lineages occurred in waves, which could be linked to the disproportionate burden of disease and sparse human population in this setting. The maintenance of bacterial gene frequency could be consistent with multilocus selection. These findings suggest that lineage-specific interventions-such as vaccines under development-should consider disease setting and, without broad cross-protection, might lead to lineage replacement. FUNDING: National Health and Medical Research Council, and Leducq Foundation.

Humans↗

Murray Valley encephalitis in an adult traveller complicated by long-term flaccid paralysis: case report and review of the literature.

Murray Valley encephalitis (MVE) virus, a mosquito-borne flavivirus, is the most common cause of viral encephalitis in the tropical 'Top End' of northern Australia. Clinical encephalitis due to MVE virus has a mortality rate of approximately 30%, with a similar proportion of patients being left with significant neurological deficits. We report the case of a 25-year-old man from the UK who acquired MVE while travelling through northern Australia. He required prolonged admission to the Intensive Care Unit and several years later remains partly ventilator-dependent, with flaccid quadriparesis. To our knowledge, this is the first reported case of MVE virus-induced flaccid paralysis in an adult in northern Australia, although it is well described in children. Paralysis was thought to be due to anterior horn cell involvement in the spinal cord and extensive bilateral thalamic destruction, both of which are well recognised complications of infection with MVE virus. Cases of flaccid paralysis with similar pathology have been described following infection with the related flavivirus Japanese encephalitis virus as well as more recently with West Nile virus. Our case highlights the potential severity of flavivirus-induced encephalitis and the importance of avoiding mosquito bites while travelling through endemic areas.

Adult↗

Efficacy of antivenom against the procoagulant effect of Australian brown snake (Pseudonaja sp.) venom: in vivo and in vitro studies.

Snake venom induced consumption coagulopathy (VICC) is a common complication of snake bite due to prothrombin activators or thrombin-like enzymes in the venom. This study aimed to determine the efficacy and dose of antivenom for treating VICC in patients envenomed by brown snakes (Pseudonaja spp.), including in vitro coagulation studies. In serial blood samples from patients with brown snake envenoming, venom and antivenom concentrations were measured using enzyme immunoassays. In vitro mixtures of brown snake venom and antivenom were used to investigate antivenom binding, neutralisation of prothrombin activity, prevention of venom-mediated clotting and effect on thrombin generation parameters using a thrombinoscope. In 27 envenomed patients the median venom concentration was 20 ng/mL (Interquartile range[IQR]:12-44 ng/mL) prior to antivenom and was not detected after antivenom administration, including 9 patients given one vial. In vitro, 200 microg/mL of antivenom bound all free venom at venom concentrations seen in patients. In vitro prothrombinase activity of the venom (using a chromogenic substrate) was not neutralised by antivenom. However, for venom concentrations seen in humans, 100 microg/mL of antivenom prevented venom clotting activity in human plasma and 479 microg/mL neutralised procoagulant venom activity measured by triggering thrombin generation. One vial of antivenom appears to be sufficient to bind and neutralise all venom in patients with severe brown snake envenoming.

Animals↗

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↗

Vibrio vulnificus and V. parahaemolyticus necrotising fasciitis in fishermen visiting an estuarine tropical northern Australian location.

Three cases of severe necrotising fasciitis due to Vibrio vulnificus (two cases) and Vibrio parahaemolyticus (one case, fatal), have occurred in Caucasian tourists while fishing at a remote tropical northern Australian estuarine area. Infections were acquired over a 4-year period during the tourist fishing season (April to July 2000-2003), when water temperatures range from 23 to 30 degrees C. They are notable for their geographical clustering in the remote western aspect of the Gulf of Carpentaria, an area characterised by sedimentary stratiform zinc-lead-silver deposits and a major mining operation. Patients presented with classical bullous cellulitis with necrotising fasciitis, accompanied by severe sepsis. Underlying risk factors were identified in each patient; in one instance, previously unrecognised haemochromatosis was diagnosed. Likely reasons for Vibrio occurrence in this particular ecological niche are discussed.

Adult↗

Treatment of snakebite in Australia: the current evidence base and questions requiring collaborative multicentre prospective studies.

Despite the wealth of anecdotes and case reports there are fundamental questions of management of snakebite in Australia that remain unresolved or for which the current evidence is limited. The efficacy in the field, potential limitations and possibility of improvements in pressure immobilisation first aid need objective studies in humans. Optimal bandage sizes, stretch and pressure for different sized limbs need further evaluation, as does the use of pressure pads. Better definitions of specific clinical envenoming syndromes attributable to individual snake species are required, including elucidation of within-genus variations, similarities and differences. Venom studies suggest this is especially important for species within the brown snake (Pseudonaja) and death adder (Acanthophis) genera. Appropriate antivenom types, doses and dosing intervals for individual snake species should be more formally studied in patients. Especially important are confirmation of the need for higher doses of brown snake antivenom, while possibly limiting unnecessarily high doses, confirmation of the critical importance of early antivenom use to prevent pre-synaptic neurotoxicity in Taipan and tiger snake bites and ascertainment of whether larger doses of antivenom are unhelpful in Taipan bites after specified time delays. Confirmation of clinical efficacy and dosing recommendations for use of tiger snake (Notechis) antivenom in envenoming from Australian copperhead (Austrelaps spp.), broad headed (Hoplocephalus spp.) and rough-scaled snakes (Tropidechis carinatus) also require formal study in patients. Other examples of clinical relevance of cross-specificity of current and future monospecific antivenoms and whether there are geographical variations in antivenom responses within species will require elucidation. Prospective multicentre collaborative studies with predefined data collection and serial venom level assays are proposed as the way forward in Australia to help resolve therapeutic uncertainties and to establish a firmer evidence base for best-practice treatment guidelines for Australasian elapid snakebite.

Adult↗

Clinical variation in melioidosis in pigs with clonal infection following possible environmental contamination from bore water.

An outbreak of melioidosis occurred in pigs on a rural property in the tropical north of the Northern Territory of Australia. The pigs were mostly asymptomatic but lesions in the parotid glands suggested an oral route of infection. Skin lesions were also common and one piglet had disseminated infection. Pulsed-field gel electrophoresis showed an identical pattern amongst Burkholderia pseudomallei isolates from the pigs, with similarity to an isolate from the unchlorinated bore water supplying the property.

Animals↗

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↗

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↗

Challenging perceptions of non-compliance with rheumatic fever prophylaxis in a remote Aboriginal community.

AIM: To identify factors that affect rheumatic fever prophylaxis for remote-living Aboriginal patients, and to determine the proportion who received adequate prophylaxis. DESIGN AND SETTING: Interview (with analysis based on principles of grounded theory) of patients with a history of rheumatic fever or rheumatic heart disease and their relatives, and health service providers in a remote Aboriginal community; audit of benzathine penicillin coverage of patients with rheumatic heart disease. PARTICIPANTS: 15 patients with rheumatic heart disease or a history of rheumatic fever, 18 relatives and 18 health care workers. RESULTS: Patients felt that the role of the clinic was not only to care for them physically, but that staff should also show nurturing holistic care to generate trust and treatment compliance. Differing expectations between patients and health care providers relating to the responsibility for care of patients absent from the community was a significant factor in patients missing injections. Neither a biomedical understanding of the disease nor a sense of taking responsibility for one's own health were clearly related to treatment uptake. Patients did not generally refuse injections, and 59% received adequate prophylaxis (> 75% of prescribed injections). CONCLUSION: In this Aboriginal community, concepts of being cared for and nurtured, and belonging to a health service were important determinants of compliance.

Anti-Bacterial Agents↗

Enzyme immunoassays in brown snake (Pseudonaja spp.) envenoming: detecting venom, antivenom and venom-antivenom complexes.

Although a commercial snake venom detection kit (SVDK) is available to distinguish between the five major snake groups in Australia, there is no assay for quantifying venom or antivenom concentrations in envenomed patients. Serum samples were obtained from patients with brown snake (Pseudonaja spp.) envenoming before and after the administration of antivenom and patients with suspected brown snake bites but no evidence of envenoming. Enzyme immunoassays (EIAs) were developed for free venom, free antivenom and the venom-antivenom complex. Standard samples measured in duplicate had a coefficient of variation of less than 10%. The EIA for venom was able to detect brown snake venom down to concentrations of 3 ng/mL. A high baseline absorbance was measured in some patients that did not change with the addition of excess antivenom to the samples. In these patients, the baseline absorbance was subtracted from all measurements to calculate the true venom concentration. The EIA for brown snake antivenom had a limit of detection of 20 microg/mL, but 50 microg/mL was used as a cut-off based on assays in patients who had not received antivenom. The EIA for venom-antivenom complexes was unable to detect these at the low venom concentrations that occurred in patients. Quantification of venom and antivenom will help to determine the dose of antivenom required to bind venom and to establish appropriate end points for antivenom treatment.

Adolescent↗

Histoplasmosis in two aboriginal patients from Australia's tropical Northern Territory.

Endemic histoplasmosis occurs uncommonly in Australia and has not previously been reported in the tropical Northern Territory, nor in Aboriginal Australian patients. We report one suspected and one confirmed case of severe disseminated histoplasmosis in Aboriginal Australians from the Northern Territory. Underlying illness included chronic cardiac disease and Type 1 diabetes mellitus, respectively, and neither patient was infected with HIV. The clinical presentations resembled malignancy. Diagnosis of histoplasmosis was made on the basis of bowel histology in Case 1, demonstrating characteristic yeasts, and lymph node histology and culture in Case 2. Histoplasmosis should be considered in relevant clinical situations, even in HIV-negative patients who have not left Australia.

Adult↗

Scabies: a ubiquitous neglected skin disease.

Scabies has been a scourge among human beings for thousands of years. Its worldwide occurrence with epidemics during war, famine, and overcrowding is responsible for an estimated 300 million people currently infested. Scabies refers to the various skin lesions produced by female mites, and their eggs and scybala that are deposited in the epidermis, leading to delayed-type hypersensitivity reaction. Recent immunological findings such as cross-reactivity with house dust mite allergens and an altered T-helper-1/T-helper-2 pattern contribute to a better understanding of the pathomechanism. Furthermore, progress in molecular biology and cloning of relevant antigens could enable the development of a diagnostic ELISA system and candidate vaccines in the near future. Typical and atypical clinical presentations with pruritus as a hallmark of scabies occur in young, pregnant, immunocompromised, and elderly patients and include bullous and crusted (Norwegian) manifestations as well as those masked by steroid use (scabies incognito). This article reviews scabies management strategies in developed countries and resource-poor communities as well as typical complications, including the emergence of resistance and drug-related adverse events. Other problems such as post-scabies eczema and reinfestation, and newer treatments such as ivermectin are also discussed.

Animals↗

Group A streptococcal infections of the skin: molecular advances but limited therapeutic progress.

PURPOSE OF REVIEW: With the sequencing of several Streptococcus pyogenes (group A Streptococcus) genomes have come major advances in understanding the pathogenesis of group A Streptococcus-associated diseases. This review focuses on group A Streptococcus skin infections and summarizes data published in the English language medical literature in 2004 and 2005. RECENT FINDINGS: Group A Streptococcus shows enormous and evolving molecular diversity driven by horizontal transmission between group A Streptococcus strains and between group A Streptococcus and other streptococci. Acquisition of prophages accounts for much of the diversity, conferring both virulence through phage-associated virulence factors and increased bacterial survival against host defences. Studies of group A Streptococcus isolates outside the US also question the generalizability of classic group A Streptococcus M serotype associations with specific disease entities such as acute rheumatic fever and necrotizing fasciitis. The distinction between throat and skin group A Streptococcus has become blurred. Although there have been few advances in treatment of group A Streptococcus skin infections, developments towards group A Streptococcus vaccines are promising. SUMMARY: The diversity of group A Streptococcus remains a challenge for vaccine development. As acute rheumatic fever and streptococcal pyoderma occur predominantly in disadvantaged populations, international funding support will be necessary for any group A Streptococcus vaccine to have a sustained impact on the global burden of disease.

Humans↗