Age: 25.0
Sex: U
Vaccine: MMR
Symptoms: Pyrexia, Rash generalised, Rhinitis, Vaccination failure
Clinical narrative: This literature marketed report as received from a physician refers to a 25 year old patient of unknown gender (case 2 in the article). The patient's medical history included ulcerative colitis, immunosuppressive medication and cerebral palsy. The patient was vaccinated with MMR vaccine (manufacturer unknown) in 1987 and 1990. Strength, dose and lot number were unknown. During a measles outbreak in 2011 suspected patients and contacts were investigated. A 22 year old female patient (also referred to as the index patient by the authors) was noted to have measles despite receipt of two doses of MMR through routine surveillance at the Department of Health and Mental Hygiene (see linked case 1405USA004782). Eighty-eight exposed contacts aged 20-65 years were identified during the index patient's infectious period, of whom 66 (75%) had documentation of immunity, 10 (11%) were not immune to measles at the time of exposure, and 12 (14%) had unknown immune status. Four additional measles patients were identified among contacts of the index patient. Three of the secondary patients, including the patient in this case were healthcare workers at a clinic where the index patient received care and were exposed to the index patient on her day of rash onset. The other secondary patient was a coworker of the index patient and was exposed to the index patient 2 days prior to her rash onset. The secondary patients had no epidemiologic links to any other patient with measles. These secondary patients had a generalized rash with onset between days 12 and 16 after exposure to the index patient. Two of the secondary patients had 2 documented doses of MMR vaccine and 2 had prior positive measles IgG antibody results. The patient in this case is one of the 2 secondary patients with documented doses of MMR vaccine (for other patient, see linked case 1405USA005755). On an unknown date in 2011 the patient developed rash, cough, conjunctivitis, coryza, diarrhea, Koplik spots and fever (38.9 degrees Celsius). Measles was confirmed by laboratory testing. On the day of rash onset the patient was negative for measles IgG and measles IgM antibodies, but the patient was positive for measles IgG and measles IGM antibodies 4 days after rash onset and 11 days after rash onset. Eleven days from rash onset, IgM/IgG index ratio was 0.3. Measles reverse transcription polymerase chain reaction from nasopharyngeal specimens was positive for measles RNA and genotype D4 was identified by sequencing. IgG activity was high 4 and 11 days after rash onset (83% and 79% respectively). Measles neutralizing antibody titer, measured by plaque reduction neutralization (PRN) test, was 1367 mIU/mL on the day of rash onset, 150.219 mIU/mL 4 days after rash onset and 175.563 mIU/mL 11 days after rash onset. Duration of rash was unknown. The patient was not hospitalized and there were no complications. Patient outcome was not specified. An additional 231 contacts were identified as exposed to the secondary patients. No tertiary cases were identified among these contacts. Per the authors, this was the first report in which a person with a verified secondary vaccine failure despite receipt of two doses of MMR was demonstrated to be capable of transmitting disease to other individuals. The laboratory results of intermediate or high-avidity IgG antibody indicated that the index patient and all of the secondary patients had past immunologic experience with measles through vaccination or natural measles infection. However, the index patient's relatively high IgM to IgG ratio was typical of a primary response, whereas those of the 4 secondary patients were consistent with a secondary immune response. The 4 secondary patients all had an early and robust antibody response within a few days after rash onset, with PRN titers 6-60 times higher than those observed after primary infection with natural disease or following measles vaccination. Despite >200 exposures identified through investigations following notification of the 4 secondary patients, no additional cases were detected. Per authors, this was in agreement with other published investigations describing a lack of transmission by documented cases of secondary vaccine failure. In each of the secondary patients, neutralizing antibody may have waned sufficiently to allow symptomatic infection, but the anamnestic response upon reexposure to measles generated a rapid and robust memory response that may have reduced their infectious period. The authors added that there were limitations to this evaluation. Although provider documentation of MMR vaccination was obtained, it was not possible to know about the quality of the vaccine received. Inappropriate storage conditions could alter the effectiveness of vaccine. It is possible that the patients never responded adequately or only achieved minimal titers following vaccination; however, the laboratory results of high-avidity IgG antibody demonstrated that all the patients had responded previously to measles virus and were not primary vaccine failures. Additional information has been requested.