Age: 22.0
Sex: F
Vaccine: MMR
Symptoms: Oropharyngeal pain, Polymerase chain reaction, Pyrexia, Rash generalised, Rhinitis
Clinical narrative: This literature marketed report as received from a physician refers to a 22 year old female patient (case 1 in article). During a measles outbreak in 2011 suspected patients and contacts were investigated. The 22 year old female patient (also referred to as the Index patient by the authors) was identified through routine surveillance at the Department of Health and Mental Hygiene. The patient's medical history was only significant for mitral valve prolapse. The patient was vaccinated with MMR vaccine (manufacturer unknown) in 1991 and 1992, at 3 years and 4 years of age respectively. Strength, dose and lot number were unknown. On an unknown date in 2011 the patient developed a generalized rash, cough, conjunctivitis, coryza, sore throat, and subjective fever and presented to an emergency room for medical care, but was not hospitalized. Measles was confirmed by laboratory testing. The patient was positive for measles IgG and measles IgM antibodies 2 days after rash onset and 9 days after rash onset. Nine days from rash onset, IgM/IgG index ration was 9.7. Measles reverse transcription polymerase chain reaction from nasopharyngeal specimens was positive for measles RNA and genotype D4 was identified by sequencing, IgG activity was intermediate (63%) 2 days after rash onset and high (100%) 9 days after rash onset. Measles neutralizing antibody titer, measured by plaque reduction neutralization test, obtained from the index patient was 81 mlU/mL in serum collected 2 days after rash and 402 mlU/mL in the follow-up serum collected 7 days later. There was no travel during the incubation period and no known sick contacts. However, the index patient worked at a theater frequented by tourists. Duration of rash was 8 days. Patient outcome was not specified. Eight-eight exposed contacts aged 20-65 years were identified during the 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 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. Two of the secondary patients had 2 documented doses of MMR vaccine (see linked cases 1405USA005754 and 1405USA005755) and 2 has prior positive measles IgG antibody results. 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  has past immunologic experience with measles through vaccination or natural measles infection. However, the index patient's relatively high IgM or IgG ration was typical of a primary response, whereas those of the 4 secondary patients were consistent with a secondary immune response. Despite high-activity IgG, the index patient did not develop the typical high neutralizing antibody titers that have been observed among previously immunized patients. The authors stated that the index patient's lower neutralizing antibody titer after infection provides a biologically plausible explanation for her ability to transmit virus. 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.