Fatal Respiratory Diphtheria Caused by ß-Lactam-Resistant Corynebacterium diphtheriae.

BACKGROUND: Diphtheria is a potentially fatal respiratory disease caused by toxigenic Corynebacterium diphtheriae. Although resistance to erythromycin has been recognized, ß-lactam resistance in toxigenic diphtheria has not been described. Here, we report a case of fatal respiratory diphtheria caused by toxigenic C. diphtheriae resistant to penicillin and all other ß-lactam antibiotics, and describe a novel mechanism of inducible carbapenem resistance associated with the acquisition of a mobile resistance element. METHODS: Long-read whole-genome sequencing was performed using Pacific Biosciences Single Molecule Real-Time sequencing to determine the genome sequence of C. diphtheriae BQ11 and the mechanism of ß-lactam resistance. To investigate the phenotypic inducibility of meropenem resistance, short-read sequencing was performed using an Illumina NextSeq500 sequencer on the strain both with and without exposure to meropenem. RESULTS: BQ11 demonstrated high-level resistance to penicillin (benzylpenicillin minimum inhibitory concentration [MIC] ≥ 256 µg/ml), ß-lactam/ß-lactamase inhibitors and cephalosporins (amoxicillin/clavulanic acid MIC ≥ 256 µg/mL; ceftriaxone MIC ≥ 8 µg/L). Genomic analysis of BQ11 identified acquisition of a novel transposon carrying the penicillin-binding protein (PBP) Pbp2c, responsible for resistance to penicillin and cephalosporins. When strain BQ11 was exposed to meropenem, selective pressure drove amplification of the transposon in a tandem array and led to a corresponding change from a low-level to a high-level meropenem-resistant phenotype. CONCLUSIONS: We have identified a novel mechanism of inducible antibiotic resistance whereby isolates that appear to be carbapenem susceptible on initial testing can develop in vivo resistance to carbapenems with repeated exposure. This phenomenon could have significant implications for the treatment of C. diphtheriae infection, and may lead to clinical failure.

Satisfactory immune response following anaphylaxis to PCECV facilitated by the use of steroids and antihistamines.

INTRODUCTION: Rabies is fatal and can cause almost certain mortality in animals and humans. Effective post-exposure prophylaxis (PEP) using the rabies vaccine remains the cornerstone for preventing disease in humans. We present the first reported case of supporting the live purified-chick-embryo-cell rabies vaccine(PCECV) administration with prophylactic high-dose corticosteroids. CASE: A 39-year-old female was at high-risk of developing rabies-like disease following a bat bite. She was commenced on PEP using PCECV. Our patient developed an anaphylactic reaction with bronchospasm and a rash following her 2nd PCECV dose. Consequently, she received 2 days of loratadine and high-dose prednisolone prior to her final vaccination. During this administration in the emergency department, our patient completed the final PCECV dose. At a two-week follow-up, our patient had no evidence of rabies and had adequate viral neutralizing antibody levels detectable on serology. DISCUSSION: Type 1 hypersensitivity reactions to PCECV are rare. Only 20 anaphylactic cases have been reported from a total of 1.1million administered doses over 8 years. Individuals at higher risk of anaphylaxis include those with a prior history of allergy to either egg white, gelatin, milk, penicillin, bee venom, or beef products. Administering high dose prophylactic corticosteroids prior to vaccination can potentially induce immune tolerance and minimize subsequent risks of hypersensitivity reactions. However, data relating to its use is extremely limited to only animal and limited human case-report data from other vaccines. CONCLUSION: We propose an alternative option which will require further research to manage vaccine-related anaphylaxis where immunization is an essential prophylactic requirement with the support of an immunologist and careful monitoring in an appropriate environment.

Informing the public health management of typhoid and paratyphoid: the Australian context.

OBJECTIVE: To examine outcomes of public health management of notified enteric fever cases in South-East Queensland over the past five years. METHODS: Notification records of typhoid and paratyphoid infection in South-East Queensland 2008-2012 (inclusive) were reviewed to determine likelihood of cases and contacts adhering to present or previous recommendations for faecal clearance/screening, duration of infectiousness of cases and extent of local transmission to contacts. RESULTS: Sixty-nine of 85 cases and 218 of 265 contacts submitted at least one faecal specimen. Cases were 2.7 (95%CI 1.2-6.0) and contacts were 4.4 (95%CI 3.0-6.4) times more likely to complete recommended faecal clearance/screening under previous compared to present guidelines (requiring more specimens). In ten cases with positive post-treatment specimens, last recorded infectiousness was 19 days to six months after notification. The documented rate of local transmission of infection was 18/1,000 contacts submitting at least one faecal specimen (95%CI 6-48/1,000). CONCLUSIONS: Local transmission risk of enteric fever in South-East Queensland is low, although small numbers of cases may have prolonged bacilli excretion post-treatment. More complex clearance/screening regimens are associated with decreased compliance. IMPLICATIONS: Pursuing extensive faecal clearance/screening regimens is unlikely to be effective in terms of public health management of enteric fever in South-East Queensland. We suggest a unified national approach focussing on cases/contacts at high risk of disease transmission.

Australian Bat Lyssavirus in a child: the first reported case.

Human infection with Australian Bat Lyssavirus is extremely rare and has not previously been reported in a child. We describe a fatal case of Australian Bat Lyssavirus in an 8-year-old child, and review the literature pertaining to the diagnosis and management of lyssavirus infection with consideration of its applicability to this emerging strain.

Evaluation of clinical management of gonorrhoea using enhanced surveillance in South East Queensland.

BACKGROUND: Gonorrhoea is the second most common notifiable sexually transmissible infection (STI) in Queensland. Notifications have been increasing since 2002. Enhanced surveillance was undertaken in this study in order to evaluate clinical management and add to understanding of the epidemiology of gonorrhoea and in South East Queensland. METHODS: Information on clinical management and an enhanced surveillance form were faxed to clinicians who notified gonorrhoea in the Brisbane Southside Population Health Unit area from 2003 to 2008. Ceftriaxone was recommended for treatment of gonorrhoea cases, as was simultaneous treatment for chlamydia, testing for other STIs and management of sexual contacts. Enhanced surveillance focussed on collecting more detailed epidemiological and clinical management information. RESULTS: A total of 909 enhanced surveillance forms were returned (response rate 72.2%). The use of ceftriaxone increased significantly over the study period from 31.3% in 2003 to 68.4% in 2008 (P < 0.05). However, there remained a considerable proportion of cases that did not receive ceftriaxone (31.6% in 2008). Simultaneous treatment for chlamydia was reported for 70.5% of cases and did not increase over the study period. A high proportion of males were not screened for high risk co-infection such as HIV (49.6%) and syphilis (51.7%). Contact tracing was initiated for 76.5% of cases and did not increase during the study period. CONCLUSIONS: Continued education of clinicians on treatment guidelines is needed. Screening of other STIs such as HIV in males with gonorrhoea and increasing contact tracing were identified as aspects of clinical management for future improvement. Overall this study provides useful insights into the clinical management of gonorrhoea in South East Queensland.

Human Hendra virus encephalitis associated with equine outbreak, Australia, 2008.

A recent Hendra virus outbreak at a veterinary clinic in Brisbane, Queensland, Australia, involved 5 equine and 2 human infections. In contrast to previous outbreaks, infected horses had predominantly encephalitic, rather than respiratory, signs. After an incubation period of 9-16 days, influenza-like illnesses developed in the 2 persons before progressing to encephalitis; 1 died. Both patients were given ribavirin. Basal serum and cerebrospinal fluid levels were 10-13 mg/L after intravenous administration and 6 mg/L after oral administration (isolate 90% inhibitory concentration 64 mg/L). Both patients were exposed to infected horses, 1 during the late incubation period in a horse. The attack rate for veterinary clinic staff exposed to infected horses was 10%. An isolate from this outbreak showed genetic heterogeneity with isolates from a concurrent, but geographically remote, outbreak and from previous outbreaks. Emergence of Hendra virus is a serious medical, veterinary, and public health challenge.

Bordetella pertussis PCR positivity, following onset of illness in children under 5 years of age.

Bordetella pertussis is a significant cause of respiratory illness and an ongoing public health problem. Pertussis polymerase chain reaction (PCR) testing has been widely utilised since 2001, especially in infants. Uncertainty exists as to how long PCR remains positive following symptom onset. Further information on the time frame for pertussis PCR testing would assist diagnosis, epidemiological research and disease control. The Brisbane Southside Population Health Unit (BSPHU) conducted a retrospective analysis of enhanced surveillance data from pertussis notifications between January 2001 and December 2005, in children less than 5 years of age, in the BSPHU reporting area with the aim to determine the possible range of duration of Bordetella pertussis PCR, from symptom onset for this age group. Of 1,826 pertussis notifications to BSPHU between January 2001 and December 2005, 155 (8.5%) were children under 5 years of age, with 115 pertussis PCR positive results. Analysis indicated a range of PCR positivity from day one to day 31 from the onset of catarrhal symptoms with most (84%) being within 21 days from onset of catarrhal symptoms. The range of PCR positivity following onset of paroxysmal cough was from day one to day 38 with most (89%) being within 14 days from the onset of paroxysmal cough. This review of pertussis PCR data in young children showed that PCR positive results generally mirrored the understood length of infectivity with regard to both catarrhal symptoms and paroxysmal cough; namely that PCR positive results were obtained at least 21 days following onset of catarrhal symptoms and at least 14 days following onset of paroxysmal cough.

"The dust hasn't settled yet": the National Q fever Management Program, missed opportunities for vaccination and community exposures.

AIMS: To determine the proportion of notifiable cases of Q fever attributable to occupational and community exposures and to identify missed opportunities for Q fever vaccination in notifications of occupational exposures. METHODS: A review of Q fever notifications to the BSPHU from January 2000 to September 2006 was undertaken. Notifications were categorised according to probable exposure source. Occupational exposures were further categorised according to reported past exposure to Q fever and Q fever vaccination status. RESULTS: One hundred and ninety-one Q fever notifications were identified, with occupational exposure reported in 106 cases and community exposure reported in 69 cases. In the occupational exposures, 76 cases (71%) were not vaccinated, 15 (14%) reported past exposure to Q fever and eight reported vaccination prior to illness onset, but vaccination status could not be independently verified. Community acquired Q fever was most commonly attributed to living or working near a high-risk industry (26, 38%), incidental exposures such as farm visits, or attending sale yards (27, 39%). CONCLUSIONS: Occupationally acquired cases of Q fever continue to be reported in significant numbers and opportunities for vaccination are being missed. There is an ongoing need to ensure that all employees in high-risk industries are screened and vaccinated. The proportion of community acquired notifications of Q fever has increased since the National Q fever Management Program started, commensurate with the decline in occupationally acquired cases. These proportions may be expected to change with the cessation of the program in Queensland in December 2006.