Measles has shown a re-emergence in Europe in recent years.1 In Spain this increase has not occurred, but the seroprevalence in young adults is lower than the ideal,2 despite the high coverage with the triple vaccine for measles, mumps, and rubella (MMR), due to its decrease over time after vaccination. For this reason, the disease now tends to appear in adults, frequently linked to imported cases and, sometimes, related to healthcare.3,4 Microbiological diagnosis is based on the combined use of reverse transcriptase polymerase chain reaction (RT-PCR) and serology.5
The purpose of this letter is to report on a case of measles in a correctly vaccinated patient, in which the microbiological diagnosis showed certain particularities (Table 1). This was a 28-year-old woman, clinical assistant in a hospital Accident and Emergency department, vaccinated with two doses of MMR, who was in contact with a patient treated at her centre for suspected mononucleosis who, after assessment in Accident and Emergency, was transferred and admitted to another health centre, in another Autonomous Region, where it was later confirmed as a case of measles. After the notification of that case, a serological study was carried out on the exposed patient mentioned here (still asymptomatic), on a serum sample extracted five days after contact to assess and confirm her immune status, with both IgM and IgG being negative for measles through CLIA (DiaSorin SpA, Saluggia, Italy), indicating home quarantine. Thirteen days after the contact, she developed fever (38 °C), which subsided within four days, followed by an enanthem and an atypical rash (arms and legs). In view of the situation, it was recommended that a sample of pharyngeal exudate be taken for study by RT-PCR of the nucleoprotein gene (RealCycler®, molecular progeny, Valencia, Spain) and a second serum sample, which was finally obtained 20 days after exposure and three days after the onset of the rash. The RT-PCR result on the pharyngeal exudate was negative. In the second serum sample (reprocessed in parallel with the first) the IgM remained negative, but a positive IgG result was found, which also had a high avidity index (>80%), determined by ELISA (Euroimmun, Lübeck, Germany).
Clinical-epidemiological characteristics of the case.
| Case | 28-year-old woman born in Spain, healthcare professional | ||
|---|---|---|---|
| Clinical presentation | Fever of 38 °C followed three days later by sore throat and an atypical skin rash not accompanied by cough, coryza or conjunctivitis | ||
| Epidemiological history | Occupational exposure with a confirmed case | ||
| 1st dose MMR | 12 years old | ||
| 2nd dose MMR | 18 years old | ||
| Sampling | |||
| Time since exposure | Time since onset of symptoms | ||
| Initial serum samples (asymptomatic, occupational risk assessment after contact with a confirmed case) | 5 | 8 | |
| Onset of symptoms (fever and skin rash 4 days later) | 13 | 0 | |
| Second serum sample and nasopharyngeal swab sample for RT-PCR | 20 | 7 | |
| Urine sample | 28 | 15 | |
| Microbiological results | |||
| First serum sample | IgM | Negative | |
| IgG | Negative | ||
| IgG avidity | Not applicable | ||
| Second serum sample | IgM | Negative | |
| IgG | Positive | ||
| IgG avidity | High (>80%) | ||
Although MMR is highly effective against measles, protection can wane over time (waning immunity) and a small proportion of vaccinated people exposed to the wild virus can become infected.6,7 The increase in vaccination coverage means that the number of immunised people is high, so it is expected that, although rare, the absolute frequency of cases in vaccinated individuals will increase in the future.6,7 MMR failures can be primary (initial lack of response) or secondary (initial response, but with a subsequent loss of protection).8 In regions with good vaccination coverage the latter are more common. The diagnosis of measles vaccine failures is complicated due to the atypical clinical presentation and laboratory results, which apparently can be confusing7,9: IgM is usually negative (since it is not the first contact with the virus [live, but attenuated in the vaccine]) and RT-PCR may not be able to detect the virus due to a lower viral load, probably due to a faster and more effective immune response that limits its ability to multiply in the previously vaccinated host. For the characterisation of vaccine failure, the IgG avidity test is crucial,7 as it differentiates between the first contact with the virus (low avidity, which in vaccinated people would indicate primary failure) and a new contact (high avidity, indicative of secondary failure in vaccinated individuals).7,9 Sometimes, as occurred with this patient, despite complete vaccination, IgG can be negative in the acute phase (probably due to the decrease to undetectable and non-protective levels). Seroconversion with specific high-avidity IgG would be the consequence of the booster effect caused by natural infection. So, in this case, which met confirmation criteria, both epidemiological (link with a measles case) and microbiological (IgG seroconversion),10 but which produced results that could be seen as discrepant (negative IgM and RT-PCR), the determination of high IgG avidity in the second sample indicated that the vaccine failure was secondary.
Conflicts of interestThe authors declare that they have no conflicts of interest in relation to this article. This work is a consequence of the surveillance activity carried out within the framework of the plan for the elimination of measles, rubella and congenital rubella syndrome in the Autonomous Region of Madrid, in Spain.
To Belén Ramos, Teresa Gómez and Rebeca Sánchez for their excellent work in the serology techniques carried out in this study.
