Kevin Barratt

Background and objective: Anti‐pyretic treatment is recommended in the management of influenza infection. In animal models anti‐pyretic treatment increases mortality from influenza. We investigated the effects of paracetamol on viral and clinical outcomes in adults with influenza infection.Methods: This is a randomized, double‐blind, placebo‐controlled trial of adults aged 18–65 years with influenza‐like illness and positive influenza rapid antigen test. Treatments were 1 g paracetamol four times a day, or matching placebo, for 5 days. Pernasal swabs were taken for influenza quantitative RT‐PCR at Baseline and Days 1, 2 and 5. Temperature and symptom scores were recorded for 5–14 days or time of resolution respectively. The primary outcome variable was area under the curve (AUC) for quantitative PCR log₁₀ viral load from Baseline to Day 5.Results: A total of 80 participants were randomized: no one was lost to follow up, and one withdrew after 4 days. There were 22 and 24 participants who were influenza PCR‐positive in placebo and in paracetamol groups respectively. Mean (SD) AUC PCR log₁₀ viral load was 4.40 (0.91) in placebo and 4.64 (0.88) in paracetamol; difference was −0.24, 95% CI: −0.78 to 0.29, P = 0.36. In all participants there were no differences in symptom scores, temperature, time to resolution of illness and health status, with no interaction between randomized treatment and whether influenza was detected by PCR.Conclusion: Regular paracetamol had no effect on viral shedding, temperature or clinical symptoms in patients with PCR‐confirmed influenza. There remains an insufficient evidence base for paracetamol use in influenza infection.Clinical trial registration: ACTRN12611000497909 at the Australian New Zealand Clinical Trials Registry.

Background. Legionnaires' disease cannot be clinically or radiographically distinguished from other causes of pneumonia, and specific tests are required to make the diagnosis. Currently, testing occurs erratically and, instead, clinicians rely on empiric treatment strategies and ignore public health implications of the diagnosis. We aimed to measure the increase in case detection of Legionnaires’ disease following the introduction of routine polymerase chain reaction (PCR) testing of respiratory specimens. PCR is the most sensitive diagnostic tool for Legionnaires’ disease. Methods. In a quasi-experimental study in Christchurch, New Zealand, we compared the number of cases of Legionnaires’ disease requiring hospitalization diagnosed during a 2-year period before the introduction of a routine PCR testing strategy (November 2008–October 2010) with a similar period after the introduction (November 2010–October 2012). With this testing strategy, all respiratory specimens from hospitalized patients with pneumonia sent to the region's sole tertiary-level laboratory were tested for Legionella by PCR, whether requested or not. Results. During November 2008 to October 2010, there were 22 cases of Legionnaires’ disease compared with 92 during November 2010 to October 2012. Of 1834 samples tested since November 2010, 1 in 20 was positive, increasing to 1 in 9 during peak Legionella season (November to January). Increasing bacterial load was associated with increasing disease severity. Conclusions. In our region, the burden of Legionnaires’ disease is much greater than was previously recognized. Routine PCR testing provides results within a clinically relevant time frame and enables improved characterization of the regional epidemiology of Legionnaires’ disease.

The primary aim of the study was to determine if the gonococcal porA pseudogene is a stable sequence target for the detection of Neisseria gonorrhoeae by PCR. A total of 240 gonococcal strains from various geographic locations were tested by porA pseudogene PCR. In addition, porA pseudogene PCR positivity rates were compared with established gonococcal assays in three Australian states. All N. gonorrhoeae isolates provided positive results in the porA pseudogene PCR. Positivity rates compared favourably with established gonococcal assays, with increased N. gonorrhoeae detection in the Northern Territory and Western Australia. The results of this multicentre study provide further evidence that the porA pseudogene is highly conserved across a diverse range N. gonorrhoeae strains and is a suitable PCR target for routine detection of N. gonorrhoeae.

Patients with meningococcal disease who seek medical attention can create a diagnostic dilemma for clinicians due to the nonspecific nature of the disease’s presentation. This study assesses the diagnostic accuracy of procalcitonin levels in the setting of meningococcal disease. Two emergency department cohorts (A and B) were studied between 2002 and 2005, during the current epidemic of serogroup B meningococcal disease in New Zealand. Cohort A consisted of 171 patients, all with confirmed meningococcal disease (84 children, 87 adults). Cohort B consisted of a large (n=1,524) consecutively recruited population of febrile patients who presented to the emergency department, 28 of whom had confirmed meningococcal disease. Within the meningococcal disease cohort (cohort A), the geometric mean procalcitonin level was 9.9 ng/ml, with levels being higher in children than in adults (21.6 vs. 4.6 ng/ml, p=0.01). The overall sensitivity of elevated procalcitonin, using a cutoff of 2.0 ng/ml in children and 0.5 ng/ml in adults, was 0.93 (95%CI: 0.88–0.96). Despite the higher cutoff level for paediatric patients, a trend towards greater sensitivity existed in children (0.96 vs. 0.90; p=0.08). Elevated procalcitonin was correlated with whole blood meningococcal load (r=0.50) and Glasgow Meningococcal Sepsis Prognostic Score (r=0.40). Within the cohort of patients who were febrile on presentation (cohort B), the specificity of elevated procalcitonin in meningococcal disease was 0.85 (95% CI: 0.83–0.87), the positive and negative likelihood ratios were 6.1 and 0.08, respectively, and the sensitivity of elevated procalcitonin (0.93; 95% CI: 0.76–0.99) was corroborated. Measurement of procalcitonin is a useful tool in patients with nonspecific febrile illnesses when the possibility of meningococcal disease is present. The diagnostic accuracy surpasses that of current early laboratory markers, allowing results to be used to guide decisions about patient management.

A dual-color LightCycler PCR assay targeting the 16S rDNA gene of Legionella spp. was established. By using two pairs of hybridization probes, Legionella spp. and Legionella pneumophila could be detected and differentiated simultaneously. With 26 culture-positive and 42 culture-negative respiratory specimens from patients with atypical pneumonia, 100% sensitivity and specificity was observed for L. pneumophila .