Community-acquired acute meningitis and encephalitis: a narrative review.

Meningitis and encephalitis are medical emergencies. Patients need prompt evaluation and immediate empiric therapy to reduce the likelihood of fatal outcomes and chronic neurological sequelae. Conjugate bacterial vaccines have significantly reduced the incidence of bacterial meningitis, especially in children. As the results of changes in patterns of bacterial drug sensitivity, ceftriaxone is now part of the recommended empiric treatment for bacterial meningitis and should be administered as early as possible. Neuroimaging delays the treatment of meningitis and is not needed in most cases. Adjunctive corticosteroid therapy is of benefit for many patients with meningitis and should be initiated in most adults before antibiotic therapy. Molecular testing can assist the specific diagnosis of encephalitis and should be based on the exposure history and geographic risk factors relevant to the patient, but non-infectious causes of encephalitis are also common. Empiric therapy for encephalitis should be directed at the most frequently identified infectious pathogen, herpes simplex virus type 1 (ie, intravenous aciclovir). Vaccines can protect against the major pathogens of childhood infections (measles, mumps, rubella, polio, varicella viruses), influenza viruses, and exotic pathogens that cause meningitis and encephalitis (rabies, Japanese encephalitis, dengue, yellow fever, tick-borne encephalitis viruses, Mycobacterium tuberculosis).

Extended spectrum beta-lactamase testing of community Enterobacteriaceae in the west of Australia: poor performance of phenotypic methods.

Expanded spectrum ß-lactamase (ESBL) producing organisms have long been recognised in institutions worldwide. Recently, community isolates producing ESBL have been reported overseas and in eastern Australia. We tested 571 consecutive Enterobacteriaceae urinary isolates from Western Australia and the Northern Territory phenotypically by calibrated dichotomous sensitivity (CDS) methods in two periods (2007 and 2012). Eleven ESBL-producing isolates from 2012 and 39 banked strains were genotyped by PCR. Twenty-six (4.6%) strains produced ESBL by CDS. Only 57.7% of CDS-confirmed ESBL strains had an initial reduced cephalosporin zone. Vitek 2 identified only nine (34.6%) CDS-ESBL strains. There was no significant change in ESBL strain prevalence over the two periods by CDS, but our laboratory information system showed a steady increase from 2007-2012 in ESBL strain prevalence (identified by multiple methods) at a rate of 0.02% per month to reach 2% by 2012. Genotyping of 50 CDS-confirmed isolates demonstrated ESBL genes in 44 (88%), mainly CTX-M genes. Twenty-five ESBL strains contained more than one ß-lactamase gene, up to a maximum of three genes. There is a rising prevalence of ESBL strains in our communities. CDS and Vitek-2 testing is neither sensitive nor specific in detecting ESBL enzymes. Routine laboratories need access to genotyping to identify and monitor ESBLs in the community.

Diagnosis of pertussis using nasopharyngeal IgA and polymerase chain reaction in specimens from outpatients in Australia.

We assessed IgA antibodies and polymerase chain reaction (PCR) for diagnosis of pertussis in nasopharyngeal aspiration (NPA) samples from outpatients in Australia. A total of 1700 patients (849 adults, 851 children) from Western Australia and the Northern Territory fulfilled the laboratory case definition for pertussis between 2004 and 2013: 732 specimens were positive by NPA IgA alone, 559 by PCR alone, and 409 by both tests. Overall, 968 cases (56.8%) were positive by PCR and 1141 cases (67.2%) by IgA [p < 0.00025]. Among pediatric patients, PCR was positive in 524 (61.3%) and IgA in 569 (67%). In 849 adult cases, the respective proportions were 52.3% and 67.4% [p < 0.00025]. The duration of cough in 507 patients was shorter in 262 pediatric cases (mean, 2.51 weeks; standard deviation [SD], 2.25) than 245 adult patients (3.27 weeks; SD, 2.79) [p = 0.0009]. PCR positivity showed a season-dependent variance (range, 5.6 to 85.9%) and peaked in the second week (71.7%) of illness. IgA antibodies peaked in the fifth week (89.5%) postinfection, and the positivity rate for NPA IgA was less variable (range, 38.3-97.2%). Nasopharyngeal Bordetella pertussis-specific IgA antibodies are valuable in diagnosis of pertussis in Australia. Reliance on PCR alone misses a significant proportion of pertussis cases, especially those with a delayed presentation.

Effect of route of infection on outcome of Toxoplasma gondii infection in hu-PBL SCID mice.

Toxoplasma gondii (T. gondii) causes serious infection, especially in immunocompromised hosts. The relevance of animal models of toxoplasmosis to human disease is unclear, but have indicated that the route of Toxoplasma infection may affect the outcome. A humanized model of toxoplasmosis of immunocompromised mice (i.e. hu-PBL SCID), using the intraperitoneal (IP) route demonstrated long-term engraftment of human cells and worsening of inflammation compared to controls. In this study, we examined the effect of route of infection on this hu-PBL SCID model using a Toxoplasma strain (i.e. DAG) isolated from an immunocompromised human. Oral infection led to an asymptomatic infection, whereas animals infected by the IP route succumbed more quickly to infection. Human cells, detected through species-specific ß-actin mRNA, were not as prominent in IP-infected animals as compared to orally infected and uninfected animals. There was evidence of control of toxoplasmosis in some orally infected animals, and this was associated with the presence of human cells in multiple tissues. Thus, the route of infection dramatically affects the outcome of infection, either by affecting parasite replication or expansion of human immune cells. Further studies of oral Toxoplasma infection using hu-PBL SCID mice may help in developing chemotherapies and immunotherapeutic strategies for toxoplasmosis.

Pandemic influenza testing at the coalface: time for reassessment?

Australian federal and state governments were advised several years ago that an influenza pandemic would overwhelm Australian public reference laboratories. It was proposed at the time that currently underused capacity in the private sector be used to enhance pandemic responses. The current outbreak of pandemic influenza has confirmed the predictions of advisors from the private sector. Future official pandemic plans should be adjusted to take into account these observations.

Evidence that the gonococcal porA pseudogene is present in a broad range of Neisseria gonorrhoeae strains; suitability as a diagnostic target.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

4: Acute community-acquired meningitis and encephalitis.

Acute meningitis and encephalitis are medical emergencies that require prompt assessment (usually by cerebral imaging and lumbar puncture) and treatment; specialist consultation is recommended. In acute meningitis, early administration of antibiotics can be life-saving (usually high-dose penicillin and/or a third-generation cephalosporin); antibiotics may be needed before referral to hospital. Emergence of penicillin and cephalosporin resistance in Streptococcus pneumoniae has necessitated more complex antibiotic regimens that include vancomycin or rifampicin for empirical treatment of meningitis. Adjunctive dexamethasone therapy may be of benefit in children with Haemophilus influenzae meningitis; there is no controlled evidence of its benefit in adults, but it could be considered in those with raised intracranial pressure. In possible encephalitis, empirical therapy with intravenous aciclovir should be given to cover herpes simplex virus (HSV) until the cause is established; HSV encephalitis may be fatal and leaves up to 50% of survivors with long-term sequelae.