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Nigel Curtis

Publications and source records attributed to Nigel Curtis.

At least 19 recordsLinked to original sources

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↗

Early detection of perinatal tuberculosis using a whole blood interferon-gamma release assay.

BACKGROUND: The diagnosis of perinatal tuberculosis (TB) is problematic because of its nonspecific presentation, the difficulty of obtaining microbiological confirmation, and the unreliability of the tuberculin skin test. Immunodiagnosis of TB has received new attention with the discovery of Mycobacterium tuberculosis-specific immunodominant antigens (early secreted antigenic target 6 [ESAT-6] and culture filtrate protein 10 [CFP-10]) that are encoded by the RD1 region of the pathogen. A whole blood assay has recently been developed to quantitatively measure interferon- gamma production by lymphocytes specific to these antigens, but its evaluation in the diagnosis of TB in infants and children has been limited to date. METHODS: In addition to routine diagnostic evaluation (tuberculin skin tests, culture of early-morning gastric aspirate samples, and chest radiographs), 2 infants with suspected perinatal TB were investigated with a whole blood interferon-gamma release assay. RESULTS: The results of the tuberculin skin tests were negative for both patients. The findings of the chest radiographs were abnormal with features suggestive of miliary TB. A whole blood interferon- gamma release assay was performed and yielded positive results within 48 h after admission to the hospital for both patients, prompting early antituberculous treatment. M. tuberculosis was cultured after 6 weeks from gastric aspirate samples collected on admission to the hospital from both infants. At 6 months of age, both infants were thriving and had acheived normal developmental milestones. CONCLUSIONS: The advent of interferon- gamma release assays may prove to be useful in the evaluation of infants with suspected perinatal TB.

Adult↗

Syphilis returns to the suburbs.

Congenital syphilis is now rare in Australia, particularly in suburban areas. The disease is both preventable and treatable, however, missed or late diagnosis can lead to catastrophic effects. We report an infant who developed congenital syphilis after multiple opportunities for preventing this condition were missed.

Anemia↗

Successful treatment of cytomegalovirus-associated haemophagocytic syndrome following paediatric orthotopic liver transplantation.

Haemophagocytic syndrome (HPS) following orthotopic liver transplantation is a rare event which is often fatal. We report here a case of HPS in association with cytomegalovirus (CMV) reactivation. The patient was treated with a combination of antiviral agents, immunomodulatory and supportive therapy which resulted in suppression of CMV infection and resolution of the haemophagocytosis.

Antiviral Agents↗

QuantiFERON-TB Gold: state of the art for the diagnosis of tuberculosis infection?

Tuberculosis (TB) remains a major threat to global health. The recently launched Global Plan to Stop Tuberculosis 2006-2015 highlights the need for accurate, simple and low-cost diagnostic tests for the detection of TB infection. For the first time in decades, new diagnostic tools have emerged that may facilitate this goal. The discovery of Mycobacterium tuberculosis-specific immunodominant antigens has led to the development of interferon gamma-release assays that have been shown to have high sensitivity and specificity for TB disease. This review focuses on the QuantiFERON-TB Gold tests and addresses the potential strengths and limitations of the current assays, summarizes the available evidence for their use and identifies areas of future research and development. Although representing an advance in TB diagnostics, with the potential to have a significant impact on global TB control, many issues remain unanswered. The cost of the tests and laboratory requirements may limit their use in developing countries. Most importantly, additional studies are needed in TB-endemic regions, particularly in high-risk persons such as children and individuals who are also co-infected with HIV.

Developing Countries↗

Variations in the protective immune response against streptococcal superantigens in populations of different ethnicity.

Superantigens (SAgs) from group A streptococcus (GAS) are potent T cell mitogens, and have been suggested to play a role in severe streptococcal disease. Neutralizing antibodies protect against SAg-mediated disease and their levels should therefore be inversely related to severe streptococcal infection. Neutralizing anti-SAg titers in patients with severe GAS infection and patients without disease were compared in two separate groups. The first group comprised patients with invasive GAS disease from New Zealand European, Maori, and Pacific Island descent. The second group comprised Aboriginal Australian individuals with rheumatic heart disease and/or a past history of acute rheumatic fever. Patients sera were tested for their ability to neutralize T cell mitogenicity of recombinant streptococcal SAgs as a measure of functional SAg-neutralizing antibody concentration. In both studies, no inverse correlation was observed between disease and the level of serum SAg-neutralizing activity. Notably, much higher levels of natural immunity to all streptococcal SAgs were found in New Zealand Maori, New Zealand Pacific Island, and Aboriginal Australian individuals, suggesting a high degree of natural exposure and seroconversion in these groups compared to the New Zealand European cohort. Levels of serum antibodies against SAgs could not be used to predict disease susceptibility in groups with existing high levels of SAg-neutralizing antibodies.

Adolescent↗

Analysis of respiratory viral coinfection and cytomegalovirus coisolation in pediatric inpatients.

OBJECTIVE: To determine (1) the rates of single infection and coinfection with 7 respiratory viruses in pediatric inpatients undergoing respiratory viral cultures, (2) the rate of cytomegalovirus (CMV) coisolation in these patients and (3) the relationship between these and length of hospital stay. METHODS: A retrospective analysis of all respiratory viral cultures undertaken at the Royal Children's Hospital, Melbourne, Australia during a 4-year period. RESULTS: A total of 6706 respiratory virus cultures were identified, of which 3955 were the first nasopharyngeal or nasal specimen taken within 48 hours of admission from inpatients younger than 18 years of age. A virus was isolated in 1444 (36.5%) specimens. Coinfection was found in only 13 (0.9%) of these culture-positive specimens (0.3% of all 3955 specimens). After adjustment for age and seasonal variation in virus isolation, rates of coinfection were lower than would have been predicted for most respiratory viruses, particularly for respiratory syncytial virus (RSV) with influenza A, and RSV with any other virus. CMV was isolated in 174 (4.4%) specimens. Rates of CMV coisolation with respiratory viruses were lower than predicted from independent infection rates, with clearest evidence for the most common virus, RSV. The length of hospital stay varied between different viruses, but there was no evidence of increased length of stay in patients with coinfection (median, 1.9 days) compared with single infection (median, 2.5 days). The length of stay was longer in patients with CMV, especially when coisolated with a respiratory virus (a median of 3.9 days for coisolation compared with a median of 2.5 days for CMV isolation alone). CONCLUSION: Coinfection with respiratory viruses is rare and in our study occurred less commonly than predicted from the independent virus isolation rates. Coisolation of CMV occurs less commonly than predicted with RSV. CMV coisolation, in contrast to respiratory virus coinfection, is associated with a longer length of stay.

Adolescent↗

Fever in children.

Fever in children is a common presenting problem in general practice, and its assessment and management are steeped in habits and teaching from the past. Evidence now suggests that treating fever is not based on the evidence that we thought--that the use of drugs has little effect both on the course of disease and the wellbeing of the child. What is the evidence for what we do and what we should do, and how do we apply this in our surgeries?

Analgesics, Non-Narcotic↗

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↗

Neonatal coxsackie B virus infection-a treatable disease?

UNLABELLED: Ten neonates with coxsackie B viral infection presented over a 3-month period. Clinical features included meningoencephalitis, thrombocytopenia, disseminated intravascular coagulopathy, cardiomyopathy, and hepatitis. Eight infants had multiorgan disease, four with severe myocardial dysfunction, of whom two died. All of the infants with severe disease developed symptoms within 7 days of age. In infants presenting within 10 days of birth, in all cases there were symptoms compatible with maternal infection prior to delivery. Severity was associated with perinatal transmission. Enteroviral polymerase chain reaction of CSF, urine, stool or throat swab was positive in nine of the ten babies. Seven of the infants were treated with a 7-day course of the new anti-picornaviral drug pleconaril (5 mg/kg 3 times daily). CONCLUSION: These cases highlight the importance of not missing coxsackie B viral infection in the differential diagnosis of the septic neonate, especially as there is now a potential treatment.

Antiviral Agents↗

Kawasaki disease and toxic shock syndrome--at last the etiology is clear?

A decade after the superantigen hypothesis for KD was first suggested, it has still not been either proven or refuted conclusively. Although initial optimism for the hypothesis was quashed by a series of published papers apparently refuting the idea, in the last few years there have been a number of good studies providing evidence in support of the superantigen hypothesis. Whether this renewed enthusiasm is justified will hopefully become clear in the near future. Ultimately, accurate diagnosis, more targeted treatment, and preventative strategies depend on the unraveling of the immunopathogenesis of this disease.

Animals↗

Chips with everything: DNA microarrays in infectious diseases.

Two developments are set to revolutionise research in and clinical management of infectious diseases. First, the completion of the human genome project together with the sequencing of many pathogen genomes, and second, the development of microarray technology. This review explains the principles underlying DNA microarrays and highlights the uses to which they are being put to investigate the molecular basis of infectious diseases. Pathogen studies enable identification of both known and novel organisms, understanding of genetic evolution, and investigation of determinants of pathogenicity. Host studies show the complexities of development and activation of both innate and adaptive immunity. Host-pathogen studies allow global analysis of gene expression during pathogenesis. Microarray technology will accelerate our understanding of the complex genetic processes underlying the interaction between microorganisms and the host, with consequent improvements in the diagnosis, treatment, and prevention of infectious diseases.

Animals↗