Monica M Lahra, Rodney P Enriquez for the National Neisseria Network
In 2015, there were 174 laboratory-confirmed cases of invasive meningococcal disease analysed by the Australian National Neisseria Network. This number was higher than that reported in 2013 and 2014, which were the lowest and second-lowest totals reported, respectively, since inception of the Australian Meningococcal Surveillance Programme in 1994. Probable and laboratory confirmed invasive meningococcal disease (IMD) is notifiable in Australia. There were 182 IMD cases notified to the National Notifiable Diseases Surveillance System in 2015, again, higher than in 2013 and 2014, which were the lowest and second-lowest totals of IMD cases recorded, respectively, by this system. Meningococcal serogrouping was able to be determined for 168/174 (97%) laboratory confirmed IMD cases. Of these, 64.2% (108 cases) were serogroup B infections, the lowest reported since 2003. Further, the number and proportion of cases of serogroup C IMD, (1.2%, 2 cases), was the lowest yet reported. By contrast, in 2015 in Australia, there was a marked increase in the number and proportion of serogroup W IMD (21.4%, 36 cases), and an increase in serogroup Y IMD (13.1%, 22 cases). The number and proportion of IMD cases caused by serogroups W and Y was the highest reported since the inception of the Australian Meningococcal Surveillance Programme in 1994. Molecular typing results were available for 140 of the 174 IMD cases. Of the 31 serogroup W IMD strains that were able to be genotyped, 25/31 (81%) were sequence type (ST)-11, and have the porA antigen encoding gene type P1.5,2, the same genotype as the hypervirulent serogroup W strain of that has been circulating in the United Kingdom and South America since 2009. In 2015, the most common serogroup B porA genotype circulating in Australia was P1.7-2,4. The primary IMD age peak was observed in adults aged 45 years or more, which was the first time that this was noted by the AMSP, whilst secondary disease peaks were observed in those aged 4 years or less, and in adolescents (15–19 years). Serogroup B cases predominated in all jurisdictions and age groups, except for those aged 45 years or over where serogroups W and Y predominated. All IMD isolates tested were susceptible to ceftriaxone and ciprofloxacin. One isolate was resistant to rifampicin. Four isolates were resistant to penicillin. Decreased susceptibility to penicillin was observed in 86% of isolates. Commun Dis Intell 2014;40(4):E503–E511.
Keywords: antibiotic resistance; disease surveillance; meningococcal disease; Neisseria meningitidis
The National Neisseria Network (NNN) in Australia is an established, collaborative network of reference laboratories in each state and territory that contribute to the laboratory surveillance system of the pathogenic Neisseria species (N. meningitidis and N. gonorrhoeae). Since 1994 the NNN has coordinated laboratory data from the examination of N. meningitidis cases of invasive meningococcal disease (IMD) for the Australian Meningococcal Surveillance Programme (AMSP).1 The AMSP is funded by the Australian Government Department of Health. The NNN laboratories supply phenotypic and genotypic data of invasive meningococci for the AMSP. These data supplement the notification data from the National Notifiable Diseases Surveillance System (NNDSS), which includes cases of probable IMD as well as laboratory confirmed IMD. The characteristics of meningococci responsible for IMD, and the associated demographic information, are important considerations for management of individual patients and their contacts; and to inform public health responses for outbreaks or case clusters, locally and nationally. The introduction of the publicly funded conjugate serogroup C meningococcal vaccine onto the National Immunisation Program in 2003 has seen a significant and sustained reduction in the number of cases of serogroup C IMD after 2003.2 However, IMD remains an issue of public health concern in Australia. In this report please note a nomenclature change for serogroup W135, which will be hereafter referred to as serogroup W in line with the accepted international nomenclature system for N. meningitidis.3
Case confirmation of invasive meningococcal disease
Case confirmation is based on isolation of N. meningitidis, or a positive nucleic acid amplification testing (NAAT) from a normally sterile site, defined as laboratory definitive evidence of IMD by the Communicable Diseases Network Australia criteria.4 Information regarding the site of infection, age and sex of the patients is collated by the NNN for the AMSP.
IMD cases are categorised on the basis of the site from which N. meningitidis was isolated, or from which meningococcal DNA was detected (blood, joint fluid, vitreous fluid). When N. meningitidis is detected from both blood and cerebrospinal fluid (CSF) from the same patient, the case is classified as one of meningitis.
Phenotyping and genotyping of Neisseria meningitidis
Phenotyping is limited to the determination of the serogroup by detection of soluble polysaccharide antigens. Genotyping of both isolates and DNA extracts is performed by sequencing of products derived from amplification of the porin genes porA, porB and FetA.
Antibiotic susceptibility testing
Isolates were tested to determine their minimum inhibitory concentration (MIC) values to antibiotics used for therapeutic and prophylactic purposes: ceftriaxone, ciprofloxacin; and rifampicin. This program uses the following parameters to define the various levels of penicillin susceptibility or resistance when determined by a standardised agar plate dilution technique: sensitive (MIC ≤ 0.03 mg/L); less sensitive (MIC 0.06–0.5 mg/L) and resistant (MIC ≥ 1 mg/L).
In 2015, there were 174 laboratory-confirmed cases of IMD analysed by the NNN, and 182 cases notified to the NNDSS. Thus, laboratory data were available for 96% of notified cases of IMD in Australia in 2014 (Figure 1). This number was higher than that reported in 2013 and 2014, which were the lowest and second-lowest totals reported, respectively, by both the NNDSS, and the AMSP. With regard to the number of cases of IMD in Australia, there has been an overall decrease from the peak reported in 2002. As in previous years, the peak incidence for IMD was in late winter and early spring (1 July to 30 September) (Table 1).
Figure 1: Number of invasive meningococcal disease cases reported to the National Notifiable Diseases Surveillance System compared with laboratory confirmed data from the Australian Meningococcal Surveillance Programme, Australia, 2015
Text version of Figure 1 (TXT 1 KB)
|Serogroup||1 January to 31 March||1 April to 30 June||1 July to 30 September||1 October to 31 December||2015|
ND: Not determined.
The highest number of laboratory confirmed cases was from Victoria (54 cases), which was higher than 2014 (33 cases), and the highest number of cases reported in this state since 2008 (61 cases).
New South Wales also recorded a rise in IMD cases in 2015 compared with 2014 (41 cases in 2015, compared with 36 cases in 2014). In contrast, Queensland recorded a fall in the number of IMD cases in 2015 (30 cases) compared with 2014 (39 cases), and this was the lowest number of cases reported in this State since the inception of the AMSP in 1994. Numbers for the other states were similar to 2014 (Table 2).
|State or territory||Serogroup||Total|
ND: Not determined
Nationally, for the first time in AMSP reporting, the peak incidence of IMD occurred in adults aged 45 years or more. This age group represented 61/174 (35%) IMD cases in 2015 (Table 3). The number of IMD cases and the proportion of cases within this age group was almost double that in 2014 (21%, 34 cases). Previously, the primary peak incidence of IMD was in children less than 5 years of age; however in 2015 they represented 23% of IMD cases, the lowest percentage of cases noted by the AMSP in this age group in any year. Between 2003 and 2014, the proportion of IMD that occurred in those less than 5 years of age in Australia ranged from 28% to 36% of cases. A secondary disease peak has also been observed in previous years among adolescents aged 15–19 years. Of the total cases of IMD, 33 (19%) were in those aged 15–19 years in 2015, which was similar to the proportion reported in the period 2006 to 2011, and 2013 to 2014 (17%, 20% respectively).
|NS: Age not stated.
ND: Not determined.
|% B of within age group||56.3||83.3||60.0||75.0||81.8||64.7||75.0||46.2||34.3|
Anatomical site of samples for laboratory confirmed cases
In 2015, diagnosis was made by a positive culture in 117/174 (67%) cases and 57/174 (33%) cases were confirmed by NAAT testing alone (Table 4).
|Specimen type||Isolate of MC||PCR positive||Total|
|PCR Polymerase chain reaction.|
|CSF +/- blood||20||33||53|
There were 53 diagnoses of meningitis based on cultures or NAAT examination of CSF either alone or with a positive blood sample. There were 115 diagnoses of septicaemia based on cultures or NAAT examination from blood samples alone (Table 4). There were 3 IMD diagnoses by positive joint fluid culture, 1 IMD diagnosis by positive eye vitreous fluid culture, 1 IMD diagnosis by positive cyst fluid culture, and 1 IMD diagnosis by NAAT where the site was not stated.
Number of cases of serogroup B, C, Y, W invasive meningococcal disease
The serogroup was determined for 168 of 174 laboratory confirmed cases of IMD (97%) in 2015 (Tables 2 and 3). The overall decrease since 2002 was initially predominantly due to a reduction in the number of cases of IMD caused by serogroup C from 2003 to 2007 following the introduction of the serogroup C vaccine. After 2009 a decline in the number of IMD cases caused by serogroup B was reported, from 194 cases in 2009, to 104 cases in 2013. In 2014, there was an increase in the number of IMD cases caused by serogroup B (n=129), but in 2015 the number of IMD cases caused by serogroup B was similar to 2013. The number of IMD cases caused by serogroup C (n=2) in 2015 was the lowest total reported by the AMSP. The number of cases of IMD caused by serogroup Y (n=22) in 2015 was the highest reported (13 cases in 2014). In contrast, the number of cases of serogroup W IMD has increased in recent years (7-16 cases in 2011-2014, compared with 4-9 cases in 2007-2010), and in 2015 there were 36 cases, the highest number reported by the AMSP, and more than double the number reported in 2014 (n=16).
Proportions of serogroup B, C, Y, W invasive meningococcal disease
Of the 168 IMD strains for which the serogroup was determined in 2015, 64.3% were serogroup B, which is the lowest overall proportion since 2003. In the years 2006 to 2012 it was 84% to 88%, and in 2013 to 2014 it was 75% to 80%. The proportion and number of IMD caused by serogroup C in 2015 was lowest since the inception of the Australian Meningococcal Surveillance Programme (1.2%).
Whilst the number and proportion of IMD attributable to serogroup B and C declined in 2015, the number and proportion of cases of serogroup Y and W have increased. In 2012 to 2014 serogroup Y accounted for 7.7% to 10.8% of IMD, higher than the proportion reported in the period 2007 to 2011: 3.5% to 5.0%. In 2015 the proportion of IMD cases caused by serogroup Y (13.1%) was the highest yet reported and the predominance (16/22, (73%) was in those aged 45 years or over.
The proportion of cases of IMD caused by serogroup W in Australia ranged from 1.8% to 4.5% in the period 2007 to 2011, and was 8.6% to 9.9% in 2013 to 2014. In 2015, this rose to 21.4% of the total cases of IMD in Australia.
In 2015 the proportion of cases of IMD caused by serogroup B in children less than 5 years, was the lowest since 2000 (Table 3, Figure 2). In young adults 20–24 years, serogroup B IMD was lower than in 2014 (83%), and lower than 2007 to 2010 and 2012 (72% to 88%) but similar to 2011 and 2013 (61% to 67%). The proportion of cases of IMD caused by serogroup B in those aged 15–19 has remained relatively stable since 2008. Serogroup B IMD was prominent in IMD in all age groups excepting 65 years or over where, serogroup Y was equally prevalent, and serogroup W slightly less so. The age group with the highest prevalence of serogroup Y IMD was those aged 65 years or over, and accounted for 12/22 total serogroup Y IMD cases (55%) in 2015. Serogroup W cases were more evenly distributed over the age groups than serogroup Y; however the age group with the highest prevalence of serogroup W IMD was those aged 65 years or over (11/37 cases, 30%), followed by those aged between 45 and 64 years (8/37 cases, 22%).
Figure 2: Number of serogroups B, Y and W cases of confirmed invasive meningococcal disease, Australia, 2015, by age
Text version of Figure 2 (TXT 1 KB)
In 2015, genotyping results were available for 140/174 (81%) IMD cases (Tables 5 and 6). The predominant porA genotypes for serogroup B IMD cases were again P1.7-2,4 (29 cases, 35% of serogroup B IMD cases that were typeable) and P1.7,16-26 (14 cases, 17% of serogroup B IMD cases that were typeable) (Figure 3). In 2014, the genotype P1.7-2,4 accounted for 18% (14 cases) of serogroup B IMD cases that were typeable, and between 2011 and 2014 was the most common genotype detected for serogroup B IMD cases that were typeable (18% to 30%).The predominant porA genotype for serogroup Y IMD cases was P1.5-1,10-1 (14 cases, 70% of serogroup Y IMD cases that were typeable). This was higher than in 2014 (6 cases, 50% of serogroup Y IMD cases that were typeable) but the overall numbers were low.
|P1.5,2||9 W||3 W||1 W||15 W||3 W|
|P1.5-1,10-1||3 B,6 Y||1 B,1 Y||6 Y||1 Y|
|P1.5-2,10-1||1 Y||2 Y|
|P1.7,16-26||3 B||4 B||1 B||5 B||1 B|
|P1.7-2,4||4 B||5 B||13 B||5 B||2 B|
|P1.18-1,3||1 W||1 B|
|P1.18-1,34||1 NG||2 B||3 B|
|P1.21,16||1 B||1 W|
|P1.22,9||1 B||2 B|
|P1.22,14||1 B||2 B||1 B||2 B|
Figure 3: Number of porA genotypes* for serogroup B in cases of invasive meningococcal disease, Australia, 2015
* Where data available.
Text version of Figure 3 (TXT 1 KB)
Of the 31 serogroup W IMD strains that were able to be genotyped, 25/31 (81%) were sequence type (ST)-11, and had the porA antigen encoding gene type P1.5,2; the same genotype as the hypervirulent serogroup W strain reported in the United Kingdom and South America since 20096,7 (Table 7).
|W genotype||Whole genome sequence type||Total|
|ST11||ST22||ST23||ST184||ST1287||Not typeable||Not tested|
Antibiotic susceptibility testing
Testing for antimicrobial susceptibility was performed for 117/174 (67%) IMD cases in 2015. All isolates tested were susceptible to ceftriaxone and ciprofloxacin. There was 1 isolate that was resistant to rifampicin (MIC=1 mg/L). Using the defined criteria, 12/117 (10.3%) isolates were fully sensitive to penicillin (MIC 0.03 mg/L or less), and 101 (86%) isolates were less sensitive to penicillin (MIC=0.06–0.5 mg/L). Four isolates were resistant to penicillin (MIC ≥ 1 mg/L).
In 2015, there were 174 cases of laboratory confirmed IMD, representing 96% of the number of notifications to the NNDSS.2 Whilst this was higher than the number of IMD cases reported in 2014, it represents the second lowest number of IMD cases reported in Australia since laboratory based surveillance (AMSP) began in 1994, and since notification data collection commenced in 1991, and represents about one-third of the peak number of IMD cases reported in Australia in 2002 (n=580). The introduction of the serogroup C vaccine to the national immunisation schedule in 2003 has resulted in a very large and sustained reduction in the number and proportion of serogroup C IMD cases in this country. In 2015, the number and proportion of serogroup C IMD cases was the lowest ever reported by the AMSP. In 2015 the majority of IMD cases continue to be caused by serogroup B strains; however the overall proportion IMD caused by serogroup B was the lowest since 2003. In early 2014, a recombinant multi-component meningococcal B vaccine became available in Australia.8 This vaccine is not on the immunisation register but is available for purchase privately. Therefore uptake is elective and the impact of its introduction is yet to be determined in this country.
All IMD isolates were susceptible to ceftriaxone and ciprofloxacin; and there was 1 isolate that was resistant to rifampicin, and 4 isolates that were resistant to penicillin. The proportion of IMD isolates with penicillin MIC values in the less sensitive category in 2015 was 86%. In previous years the range was 62% to 75% in 1996–2006; 67% to 79% in 2007–2009; and 78% to 88% in 2010–2014, thus indicating an ongoing increasing trend in penicillin MIC values of IMD isolates. The incidence of penicillin resistance in N. meningitidis in Australia however, remains low.
In 2015, a number of changes in IMD epidemiology were observed in Australia. There was a notable increase in the number of IMD cases caused by serogroups W and Y, the highest yet reported by the AMSP, and these were the predominant serogroups causing IMD in those aged 65 years or over. In addition, in 2015, the primary peak of IMD was observed for the first time in adults aged 45 years or more, because of the increased number of serogroup W and serogroup Y IMD cases in this age group. Secondary disease peaks were observed in those aged 4 years or less, and in adolescents (15–19 years).
In 2015, 21% of all IMD notifications were serogroup W, with the highest proportion of cases in New South Wales (22%), Victoria (17%), and Queensland (17%). Whole genome sequencing found that the predominant circulating strain of serogroup W in Australia in 2015, (25/31, 81%), was sequence type (ST)-11, and had the porA antigen encoding gene type P1.5,2. This is the same genotype as the hypervirulent serogroup W strain that emerged in the United Kingdom and South America in 20096,7 and has spread to now account for 25% of IMD in the United Kingdom in 2014–2015, and 59% of all cases in Chile in 2012. This serogroup W strain is now considered endemic in these regions, is associated with atypical presentations, more severe clinical disease and a higher case fatality rate.7 In these regions, the initial increase in IMD was seen in older adults, but was subsequently reported in all age groups, particularly in adolescents and infants.9 In response, vaccination programs have been implemented in both the United Kingdom and in Chile.6,10 The increase in cases of serogroup W IMD is of significant concern and the NNN is working on further investigations with the Australian Government Department of Health and the Communicable Diseases Network Australia and is closely monitoring the phenotypic and genotypic features of N. meningitidis causing IMD in Australia. Additional investigations including whole genome sequencing of all Serogroup W are in place to enhance surveillance practices. The AMSP data are used for informing treatment protocols and to inform the need for and monitor the effect of disease prevention strategies.
Meningococcal isolates were received in the reference centres from many laboratories throughout Australia. The considerable time and effort involved in forwarding these isolates is recognised and these efforts are greatly appreciated. These data could not have been provided without this assistance and the help of clinical colleagues and public health personnel. The Australian Government Department of Health provided funding for the National Neisseria Network.
Members of the AMSP in 2015 were: John Bates, Helen Smith and Vicki Hicks, Public Health Microbiology, Forensic and Scientific Services, Coopers Plains, Queensland; Monica Lahra, Rodney Enriquez; Tiffany Hogan; Ratan Kundu and Athena Limnios, Department of Microbiology, SEALS, The Prince of Wales Hospital, Randwick, New South Wales; Dr Michael Maley, Robert Porritt and Joanne Mercer, Department of Microbiology and Infectious Diseases, SSWPS, Liverpool, New South Wales; Kerrie Stevens, The Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria; Andrew Lawrence, Microbiology and Infectious Diseases Department, SA Pathology, Adelaide, South Australia; Jane Bew, Leanne Sammels and Tony Keil, Department of Microbiology, Princess Margaret Hospital for Children, Subiaco, Western Australia; Belinda McEwan Belinda Chamley and Dr McGregor Department of Microbiology and Infectious Diseases, Royal Hobart Hospital, Hobart, Tasmania; Rob Baird, Kevin Freeman and microbiology staff, Microbiology Laboratory, Territory Pathology, Royal Darwin Hospital, Tiwi, Northern Territory; Angelique Clyde-Smith and Peter Collignon, Microbiology Department, Canberra Hospital, Garran, Australian Capital Territory.
Participants in the 2015 AMSP to whom isolates and samples should be referred, and enquiries directed, are listed below.
Australian Capital Territory
P Collignon, S Bradbury Microbiology Department The Canberra Hospital Yamba Drive Garran ACT 2605 Telephone: +61 2 6244 2414 Email: firstname.lastname@example.org
New South Wales
MM Lahra, RP Enriquez, EA Limnios, TR Hogan, RL Kundu Microbiology Department, SEALS, The Prince of Wales Hospital Barker Street, Randwick NSW 2031 Telephone: +61 2 9382 9084 Facsimile: +61 2 9382 9310 Email: email@example.com
M Maley, J Mercer, R Porritt Department of Microbiology and Infectious Diseases SSWPS Locked Mail Bag 7090 Liverpool BC NSW 1871 Telephone: +61 8738 5124 Facsimile: +61 2 8738 5129 Email: Joanne.Mercer@sswahs.nsw.gov.au or Robert.Porritt@sswahs.nsw.gov.au
R Baird, K Freeman Microbiology Laboratory Territory Pathology Royal Darwin Hospital Tiwi NT 0810 Telephone: +61 8 8922 8167 Facsimile: +61 8 8922 7788 Email: firstname.lastname@example.org
J Bates, H Smith, V Hicks Public Health Microbiology Forensic and Scientific Services 39 Kessels Road Coopers Plains Qld 4108 Telephone: +61 7 3274 9101 Facsimile: +61 7 3274 9175 Email: email@example.com
A Lawrence Microbiology and Infectious Diseases SA Pathology Frome Road, Adelaide, SA 5000 Telephone: +61 8 2223503 Facsimile: +61 8 2223543 Email: firstname.lastname@example.org
B McEwan, B Chamley Department of Microbiology and Infectious Diseases Royal Hobart Hospital 48 Liverpool Street Hobart Tasmania 7000 Telephone: +61 3 6222 8656 Email: email@example.com
K Stevens Microbiological Diagnostic Unit Public Health Laboratory Department of Microbiology and Immunology The University of Melbourne Parkville Victoria 3052 Telephone: +61 3 8344 5701 Facsimile: +61 3 8344 7833 Email: firstname.lastname@example.org
AD Keil, J Bew, L Sammels Department of Microbiology Princess Margaret Hospital for Children 1 Thomas Street Subiaco WA 6008 Telephone: +61 8 9340 8273 Facsimile: +61 8 9380 4474 Email: email@example.com or firstname.lastname@example.org
Monica M Lahra1,2
Neisseria Reference Laboratory and World Health Organisation Collaborating Centre for STD, Sydney. Department of Microbiology, South Eastern Area Laboratory Services, The Prince of Wales Hospital, Randwick, New South Wales.
School of Medical Sciences, Faculty of Medicine, The University of New South Wales, New South Wales
Corresponding author: Professor Monica Lahra, Microbiology Department, SEALS, Director, Neisseria Reference Laboratory and WHO Collaborating Centre for STD, Level 4, Campus Centre, The Prince of Wales Hospital, RANDWICK NSW, 2031. Email: email@example.com
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- Abad R, Lopez E, Debbag R, Vázquez JA. Serogroup W meningococcal disease: global spread and current affect on the Southern Cone in Latin America. Epidemiol Infect 2014;142(12):2461–2470.
- Ladhani SN, Beebeejaun K, Lucidarme J, Campbell H, Gray S, Kaczmarski E, et al. Increase in endemic Neisseria meningitidis capsular group W sequence type 11 complex associated with severe invasive disease in England and Wales. Clin Infect Dis 2015;60(4):578–585.
- Australian Government Department of Health. Meningococcal disease. Immunise Australia Program. 2015. Accessed 2016. Available from: http://www1.health.gov.au/internet/immunise/publishing.nsf/Content/immunise-meningococcal
- Araya P, Fernandez J, Del Canto F, Seoane M, Ibarz-Pavón AB, Barra G, et al. Neisseria meningitidis ST-11 clonal complex, Chile 2012. Emerg Infect Dis 2015;21(2):339–341.
- Campbell H, Saliba V, Borrow R, Ramsay M, Ladhani SN. Targeted vaccination of teenagers following continued rapid endemic expansion of a single meningococcal group W clone (sequence type 11 clonal complex), United Kingdom 2015. Euro Surveill 2015;20(28):pii=21188.