Investigation and response to an outbreak of Neisseria meningitidis serogroup Y ST-1466 urogenital infections, Australia.

Abstract: In 2023, an increased number of urogenital and anorectal infections with Neisseria meningitis serogroup Y (MenY) were reported in New South Wales (NSW). Whole genome sequencing (WGS) found a common sequence type (ST-1466), with limited sequence diversity. Confirmed outbreak cases were NSW residents with a N. meningitidis isolate matching the cluster sequence type; probable cases were NSW residents with MenY isolated from a urogenital or anorectal site from 1 July 2023 without WGS testing. Of the 41 cases, most were men (n = 27), of whom six reported recent contact with a female sex worker. Five cases were men who have sex with men and two were female sex workers. Laboratory alerts regarding the outbreak were sent to all Australian jurisdictions through the laboratories in the National Neisseria Network. Two additional states identified urogenital MenY ST-1466 infections detected in late 2023. Genomic analysis showed all MenY ST-1466 sequences were interspersed, suggestive of an Australia-wide outbreak. The incidence of these infections remains unknown, due to varied testing and reporting practices both within and across jurisdictions. Isolates causing invasive meningococcal disease (IMD) in Australia are typed, and there has been no MenY ST-1466 IMD recorded in Australia to end of March 2024. Concerns remain regarding the risk of IMD, given the similarity of these sequences with a MenY ST-1466 IMD strain causing a concurrent outbreak in the United States of America.

High prevalence of ceftriaxone-resistant and XDR Neisseria gonorrhoeae in several cities of Cambodia, 2022-23: WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP).

Objectives: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern. Ceftriaxone is the last effective and recommended option for empirical gonorrhoea therapy worldwide, but several ceftriaxone-resistant cases linked to Asia have been reported internationally. During January 2022-June 2023, the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) investigated N. gonorrhoeae AMR and epidemiological factors in patients from 10 clinical sentinel sites in Cambodia. Methods: Urethral swabs from males with urethral discharge were cultured. ETEST determined the MIC of five antimicrobials, and EGASP MIC alert values and EUCAST breakpoints were used. EGASP demographic, behavioural and clinical variables were collected using a standardized questionnaire. Results: From 437 male patients, 306 had positive N. gonorrhoeae cultures, AMR testing and complete epidemiological data. Resistance to ceftriaxone, cefixime, azithromycin and ciprofloxacin was 15.4%, 43.1%, 14.4% and 97.1%, respectively. Nineteen (6.2%) isolates were resistant to all four antimicrobials and, accordingly, categorized as XDR N. gonorrhoeae. These XDR isolates were collected from 7 of the 10 sentinel sites. No EGASP MIC alert values for gentamicin were reported. The nationally recommended cefixime 400 mg plus azithromycin 1 g (65.4%) or ceftriaxone 1 g plus azithromycin 1 g (34.6%) was used for treatment. Conclusions: A high prevalence of ceftriaxone-resistant, MDR and XDR N. gonorrhoeae in several cities of Cambodia were found during 2022-23 in WHO EGASP. This necessitates expanded N. gonorrhoeae AMR surveillance, revision of the nationally recommended gonorrhoea treatment, mandatory test of cure, enhanced sexual contact notification, and ultimately novel antimicrobials for the treatment of gonorrhoea.

Rapid expansion of Neisseria gonorrhoeae ST7827 clone in Australia, with variable ceftriaxone phenotype unexplained by genotype.

BACKGROUND: Neisseria gonorrhoeae is identified as a priority pathogen due to its capacity to rapidly develop antimicrobial resistance (AMR). Following the easing of SARS-CoV-2 pandemic travel restrictions across international borders in the state of New South Wales (NSW), Australia, a surge of gonococcal isolates with raised ceftriaxone MIC values were detected. METHODS: All N. gonorrhoeae isolates (n = 150) with increased ceftriaxone MIC values in NSW between 1 January 2021 and July 2022 from males and females from all sites were sequenced. RESULTS: A new emergence and rapid expansion of an N. gonorrhoeae ST7827 clone was documented within NSW, Australia and provides further evidence of the ability of N. gonorrhoeae to undergo sufficient genomic changes and re-emerge as a geographically restricted subclone. Mapping AMR determinants to MIC results did not reveal any genomic pattern that correlated with MIC values. CONCLUSIONS: The rapid dissemination and establishment of this clone at the population level is a new and concerning demonstration of the agility of this pathogen, and underscores concerns about similar incursions and establishment of MDR clones. Moreover, it is notable that in this context the AMR genotype-phenotype correlates remain unclear, which requires further investigation to enable better understanding of genomic aspects of AMR in N. gonorrhoeae.

Meningococcal disease epidemiology in Australia 10 years after implementation of a national conjugate meningococcal C immunization programme.

Australia implemented conjugate meningococcal C immunization in 2003 with a single scheduled dose at age 12 months and catch-up for individuals aged 2-19 years. Several countries have recently added one or more booster doses to their programmes to maintain disease control. Australian disease surveillance and vaccine coverage data were used to assess longer term vaccine coverage and impact on invasive serogroup C disease incidence and mortality, and review vaccine failures. Coverage was 93% in 1-year-olds and 70% for catch-up cohorts. In 10 years, after adjusting for changes in diagnostic practices, population invasive serogroup C incidence declined 96% (95% confidence interval 94-98) to 0·4 and 0·6 cases/million in vaccinated and unvaccinated cohorts, respectively. Only three serogroup C deaths occurred in 2010-2012 vs. 68 in 2000-2002. Four (<1/million doses) confirmed vaccine failures were identified in 10 years with no increasing trend. Despite published evidence of waning antibody over time, an ongoing single dose of meningococcal C conjugate vaccine in the second year of life following widespread catch-up has resulted in near elimination of serogroup C disease in all age groups without evidence of vaccine failures in the first decade since introduction. Concurrently, serogroup B incidence declined independently by 55%.

Detection of Neisseria gonorrhoeae Isolates from Tonsils and Posterior Oropharynx.

We examined the factors influencing gonorrhea detection at the pharynx. One hundred men infected with Neisseria gonorrhoeae were swabbed from the tonsils and posterior oropharynx. N. gonorrhoeae was reisolated from the tonsils and posterior oropharynx in 62% and 52%, respectively (P = 0.041). Culture positivity was greater with higher gonococcal DNA loads at the tonsils (P = 0.001) and oropharynx (P < 0.001). N. gonorrhoeae can be cultured from the tonsils and posterior oropharynx with greater isolation rates where gonococcal loads are higher.

Polymerase chain reaction-based screening for the ceftriaxone-resistant Neisseria gonorrhoeae F89 strain.

Emergence and spread of Neisseria gonorrhoeae resistant to extended spectrum cephalosporins is a major problem threatening treatment of gonorrhoea and is further highlighted by the recent report of a second ceftriaxone-resistant N. gonorrhoeae strain (F89) in Europe, initially observed in France and subsequently identified in Spain. N. gonorrhoeae antimicrobial resistance (AMR) surveillance has acquired new importance and molecular tools have the potential to enhance bacterial culture-based methods. In this study, we established a polymerase chain reaction (PCR) protocol for direct detection of the F89 strain. A key component of this screening protocol was the development of a hybridisation probe-based melting curve analysis assay (mosaic501-hybPCR) to detect the presence of an A501P substitution on the N. gonorrhoeae mosaic penicillin binding protein 2 (PBP2) sequence, an important characteristic of the F89 strain. The mosaic501-hybPCR was evaluated using plasmid-derived positive controls (n=3) and characterised gonococcal (n=33) and non-gonococcal (n=58) isolates. The protocol was then applied to 159 clinical specimens from Sydney, Australia, collected during the first half of the year 2012 that were N. gonorrhoeae PCR-positive. Overall, the results indicate that the PCR-based protocol is suitable for direct detection of the N. gonorrhoeae F89 strain in non-cultured clinical samples. It therefore provides an additional tool to aid investigations into the potential spread of F89 strain throughout Europe and elsewhere.

Maternal versus fetal inflammation and respiratory distress syndrome: a 10-year hospital cohort study.

OBJECTIVES: To determine the impact of maternal and fetal intrauterine inflammatory responses (chorioamnionitis and umbilical vasculitis) on the development of neonatal respiratory distress syndrome (RDS) in preterm infants. DESIGN, SETTING AND SUBJECTS: The study included all infants <30 weeks' gestation born at the Royal Prince Alfred Hospital, Sydney, Australia, and admitted to neonatal intensive care from 1992 to 2001. Those without placental examination were excluded. Antenatal and perinatal data were extracted from prospectively kept hospital databases and correlated with the independent, central neonatal database. Placentae were examined prospectively using a standardised, semi-quantitative method. MAIN OUTCOME MEASURE: A diagnosis of neonatal RDS. RESULTS: There were 766 eligible babies and 724 (94.5%) had placental examination. The mean (SD) gestational age of the cohort was 27.1 (1.6) weeks. Antenatal maternal steroids were given to 93.6%. Histological chorioamnionitis alone was evident in 19.1% of infants, and chorioamnionitis with umbilical vasculitis in 30.2%. Regression analysis showed that increasing gestational age (adjusted odds ratio (OR) 0.72, 95% CI 0.64 to 0.81), chorioamnionitis (adjusted OR 0.49, 95% CI 0.31 to 0.78), and chorioamnionitis with umbilical vasculitis (adjusted OR 0.23, 95% CI 0.15 to 0.35) were associated with a significant reduction in RDS. Factors associated with increased odds of RDS were multiple gestation (twin or triplet pregnancies), pregnancy-induced hypertension and an Apgar score <4 at 1 minute. CONCLUSIONS: Maternal and fetal intrauterine inflammatory responses are both protective for RDS. The presence of chorioamnionitis with umbilical vasculitis is associated with a markedly greater reduction of RDS than chorioamnionitis alone.

Survival after pulmonary edema due to enterovirus 71 encephalitis.

BACKGROUND: A distinctive pattern of enterovirus 71 (EV71) infection, characterized by fever, exanthem, acute pulmonary edema (PE), brainstem encephalitis, and flaccid paresis, affects infants and young children. Most die rapidly owing to respiratory failure and fulminant PE. METHOD: The authors report short- and long-term outcome of six survivors of the acute illness. RESULTS: In the context of acute PE and widespread weakness, recognition of the underlying neurologic disorder was facilitated by the distinctive pattern of MRI signal abnormalities in posterior pons and medulla. EV71-specific PCR of clinical samples helped confirm the diagnosis. Acute PE was managed with mechanical ventilation, afterload reduction, and inotrope support, and resolved completely over days. One patient with minimal neurologic recovery died 9 weeks after disease onset. The other patients have residual neurologic dysfunction, varying from subtle monoparesis to severe bulbar dysfunction, central and peripheral respiratory failure, and flaccid quadriparesis. Faster neurologic recovery was associated with less long-term deficit. Long-term outcome was similar in patients treated with and without pleconaril or IV immunoglobulin. Three long-term survivors treated with IV corticosteroids had less severe long-term neurologic disability than two not treated with steroids. CONCLUSION: Acute pulmonary edema and encephalomyelitis occurs with EV71 infection in infants. Long-term neurologic outcome varied from minor, focal weakness to profound, global motor dysfunction with respiratory failure.

The quality of communication between hospitals and general practitioners: an assessment.

The objective of this study was to assess the quality of communications between hospitals and general practitioners (GPs). The proportion of medical records in which the patient's general practitioner (GP) was identified, the accuracy of medications recorded in the discharge summary, the proportion of GPs who received discharge summaries, and the timeliness of receipt of discharge summaries were all evaluated. Discussions were held with all stakeholders, the literature was reviewed and GPs were surveyed to identify potential measures of quality. These were then trialled to assess their utility and practicability. Timeliness, issues that required follow-up and treatment provided in hospital were of greatest importance to general practitioners. The GP's name was recorded in 88% of audited records. Few inaccuracies were detected in the medications recorded in the discharge summaries, and GPs received 77% of discharge summaries. Methods similar to those used in this study might be broadly applied to improve the quality of discharge communication throughout Australia.

Eight-year outcome of universal screening and intrapartum antibiotics for maternal group B streptococcal carriers.

OBJECTIVES: To report the outcome of intervention to reduce early-onset group B streptococcal disease (EOGBSD) at a tertiary maternity hospital in Sydney and to review all cases of EOGBSD since intervention to improve outcomes further. METHODOLOGY: A prospective study was made of all cases of EOGBSD in the 16 months before and 8 years after an intervention that comprised universal screening and intrapartum ampicillin for all maternal carriers of group B streptococcus. Carriers were detected by screening all women at 28 weeks, or 24 weeks with known risk factors for preterm birth, by low vaginal swab, cultured onto blood agar and treated with intravenous ampicillin in labor, 1 g every 6 hours until delivery. Women with a routine midstream urine test positive for group B streptococcus, a previous neonate with EOGBSD, or preterm labor with an unknown carrier status were also treated. EOGBSD was detected by screening all neonates with maternal and/or neonatal risk factors for sepsis. RESULTS: The incidence of blood culture-positive EOGBSD for all live births before intervention was 1.4 per 1000 compared with a rate after intervention of 0.2 per 1000 live births. The incidence, if there were clinical signs of infection and the urine tested positive for streptococcal antigen, decreased from 3.5 per 1000 before intervention to 0.6 per 1000 live births. There was a statistically significant reduction in neonatal morbidity outcomes after intervention, including requirement for admission and treatment in a neonatal unit and the need for ventilation. An audit indicated that by the 8th year, 90% of all pregnant women were screened by a low vaginal swab at 28 weeks and 10.5% were carriers. After intervention, of the 28 neonates with EOGBSD, 64% were associated with departure from the protocol. CONCLUSION: The intervention has coincided with a significant decrease in the incidence of blood culture-positive EOGBSD to 0.2 and urine streptococcal antigen-positive disease to 0. 6 per 1000 live births. The 84% reduction in EOGBSD has been obtained by treating 244 neonates in labor to prevent disease in one neonate. Additional reduction seems possible by improving the compliance by staff with the protocol. By contrast, before intervention and in maternity units throughout Australia with no intervention, the rates for EOGBSD remain largely unchanged at approximately 2 per 1000 live births.