The importance of molecular testing to confirm measles, mumps and rubella in immunised individuals
Authors: David J Speers and Gary K Dowse
Published online: 6 April 2015
To the Editor: Despite high vaccination coverage, Australians remain at risk of measles, mumps and rubella, either while travelling to endemic countries or from domestic exposure to imported cases. Those most at risk include incompletely vaccinated adults and children whose parents choose not to have them vaccinated. Additionally, immunity generated by vaccination (rather than natural infection) may be less protective, especially if only one vaccine dose is received.1,2
When measles, mumps and rubella were commonly encountered, their clinical features were well recognised, but far fewer cases are now seen, diminishing clinical acumen and the positive predictive value of a clinical diagnosis. Further, the relative proportion of cases in previously vaccinated individuals has increased, making the clinical diagnosis more difficult as these cases may present atypically.1,3
With this clinical uncertainty, laboratory confirmation assumes greater importance.4 However, the IgM response can take several days to appear and can be attenuated or completely absent in post-vaccination infection,1,2 necessitating molecular detection methods to confirm the diagnosis.2-4 Polymerase chain reaction (PCR) testing has been shown to contribute significantly to laboratory confirmation of measles2,5 and mumps3,4 in highly vaccinated populations.
We investigated the vaccination status and mode of laboratory confirmation of notified cases of measles, mumps and rubella in Western Australia over almost 10 years, from January 2001 to September 2010. During this period, 82 cases of measles, 335 of mumps and 38 of rubella were notified to the Department of Health. Of these, eight patients (10%) with measles, 117 (35%) with mumps and four (11%) with rubella were fully vaccinated; 16 (20%), 39 (12%) and five (13%), respectively, were partially vaccinated; and 46 (56%), 53 (16%) and 22 (58%), respectively, were unvaccinated. Thirty-two per cent of measles, 49% of mumps and 89% of rubella cases were confirmed by IgM serological testing alone; 34%, 2% and 3%, respectively, were confirmed by serological testing and PCR; and 20%, 38% and 3%, respectively, were confirmed by PCR alone (IgM not detected or not requested). A further 15% of measles, 10% of mumps and 5% of rubella cases were diagnosed using clinical and epidemiological criteria, without testing. Overall, when laboratory-confirmed cases were stratified by vaccination status, the proportion confirmed by PCR alone increased from 18% in the unvaccinated to 71% in the fully vaccinated, including from 21% to 63% for measles, and 22% to 74% for mumps, respectively (Box).
These data confirm the increased number of measles and mumps cases diagnosed by PCR rather than serological testing among people who are fully vaccinated compared with the unvaccinated group. Diagnosis by PCR allows virus genotyping, which is important for epidemiological purposes2 and can distinguish wild-type measles virus from the vaccine strain when vaccine is used for post-exposure prophylaxis.5 We recommend collection of respiratory specimens, whole blood and/or urine for PCR diagnosis, in addition to serological testing, for laboratory diagnosis in suspected cases of measles, mumps and rubella.
Laboratory-confirmed cases of measles, mumps and rubella in Western Australia, January 2001 to September 2010
Vaccination status | Laboratory confirmation | Measles (n = 70) | Mumps (n = 300) | Rubella (n = 36) | Total (%) | ||||||||||
Fully vaccinated | Serological | 3 | 26 | 3 | 32 (28%) | ||||||||||
PCR | 5 | 75 | 0 | 80 (71%) | |||||||||||
Both | 0 | 1 | 0 | 1 (1%) | |||||||||||
Partially vaccinated | Serological | 5 | 17 | 4 | 26 (46%) | ||||||||||
PCR | 3 | 15 | 0 | 18 (32%) | |||||||||||
Both | 8 | 3 | 1 | 12 (21%) | |||||||||||
Not vaccinated | Serological | 13 | 39 | 20 | 72 (69%) | ||||||||||
PCR | 7 | 11 | 1 | 19 (18%) | |||||||||||
Both | 14 | 1 | 0 | 15 (14%) | |||||||||||
Unknown | Serological | 5 | 82 | 7 | 94 (90%) | ||||||||||
PCR | 1 | 27 | 0 | 28 (24%) | |||||||||||
Both | 6 | 3 | 0 | 9 (8%) | |||||||||||
PCR = polymerase chain reaction.
Competing interests
No relevant disclosures.
Acknowledgements
We thank the clinicians and laboratory and public health staff involved in the diagnosis, testing and follow-up of these cases.
References
- Rota JS, Hickman CJ, Sowers SB, et al. Two case studies of modified measles in vaccinated physicians exposed to primary measles cases: high risk of infection but low risk of transmission. J Infect Dis 2011; 204 Suppl 1: S559-S563. _Ref413400013
- Vainio K, Steen TW, Arnesen TM, et al. Measles virus genotyping an important tool in measles outbreak investigation in Norway, 2011. Euro Surveill 2012; 17: 20340. _Ref413400015
- Hatchette T, Davidson R, Clay S, et al. Laboratory diagnosis of mumps in a partially immunized population: the Nova Scotia experience. Can J Infect Dis Med Microbiol 2009; 20: e157-e162. _Ref413400033
- Bitsko RH, Cortese MM, Dayan GH, et al. Detection of RNA of mumps virus during an outbreak in a population with a high level of measles, mumps, and rubella vaccine coverage. J Clin Microbiol 2008; 46: 1101-1103. _Ref413400038
- Aoki Y, Mizuta K, Ikeda T et al. Isolation of vaccine-derived measles viruses from children with acute respiratory infection. Tohoku J Exp Med 2013; 230: 111-115. _Ref413400130