Measles outbreak in a highly vaccinated population

Measles outbreak in a highly vaccinated population

Centers for Disease Control and Prevention
Eva Avramovich, Viki Indenbaum, Meital Haber, Ziva Amitai, Evgeny Tsifanski1, Sahar Farjun,
Alona Sarig, Adi Bracha, Karina Castillo, Michal Perry Markovich, Inbal Galor
October 26 2018


On August 6, 2017, the Israeli Defense Force Public Force (IDFPHB) was informed of two suspected measles cases. IDFPHB conducted an epidemiological investigation, which identified nine measles cases in a population with measles vaccination coverage. All measles patients had signs and symptoms compatible with the modified measles (i.e., less severe disease with mild rash, fever or both, with or without other typical typical measles symptoms). A total of 1.392 contacts were identified and 162 received post-exposure prophylaxis (PEP) with the measles-mumps-rubella vaccine (MMR); the remaining contacts were followed for 21 days (an incubation period). No tertiary cases have been identified.


Investigation and results

The first two cases (in patients A and B) were reported on August 6, 2017. Both cases occurred in soldiers who developed mild symptoms (fever and maculopapular rash) on August 4 and subsequently were hospitalized in isolation in a civil hospital. Urine and serum specimens were sent to Israel's National Measles and Rubella Laboratory (NMRL). Neither patient had traveled or had known exposure to measles, nor was there an obvious epidemiological link between the cases. Both patients had 2 doses of the MMR vaccine. Cases in patients A and B were confirmed serologically and with urine polymerase chain reaction (PCR) tests on August 7 and August 9, respectively (Table). A third patient with mild symptoms (patient C) was reported by NMRL staff to IDFPHB on August 7 after confirmation of urinary PCR. Patient C, a 19-year-old soldier, was the partner of patient A and reported receiving 2 doses of the measles vaccine.

IDFPHB has undertaken an epidemiological investigation to determine the source of infection, identify contacts and recommend PEP. Since all three cases appeared within days of each other, a common source of infection was suspected.

Investigators learned that patients A, B and C had visited the same crowded mixed civil-military clinic on July 24 during the same hour; therefore, the clinic was suspected of being the site of exposure. To evaluate this hypothesis, investigators examined the medical records of all patients treated at the clinic on July 24 during the same visit as patients A, B and C. One patient examined in the clinic was a 21-year-old soldier born in Ukraine who had been evaluated for fever and rash; measles was not suspected at the time. The investigation found that he had returned to Israel three days before visiting the clinic, having traveled to three European countries (France, Germany and Ukraine) with ongoing measles epidemics. Since he was suspected of being the primary patient, his serum sample was forwarded to NMRL, where measles was confirmed serologically.

The primary patient would have been contagious from about 4 days before until 4 days after the onset of the rash. Since more than 14 days had passed since the July 24 clinical exposure, it was predicted that some exposed clinical contacts (in addition to patients A, B and C) may have already developed measles. Therefore, the medical records of all soldiers who went to the clinic on July 24, as well as other military contacts from the primary patient, were reviewed daily for 21 days starting on July 24. The goal was to identify the occurrence of fever, rash, conjunctivitis, or Koplik points between contacts.

For the purpose of the investigation, a suspected case of measles was defined as the presence of a febrile rash disease. Confirmed measles was defined as a positive test for measles by urinary PCR or positive / equivocal immunoglobulin M, and a probable case was defined as a suspect case with suggestive laboratory results (positive immunoglobulin G [IgG] with high IgG avidity, indicative of a past immunological response to the vaccine or measles infection).

The review of the medical records led to a further evaluation of 14 patients, including a history of vaccination, exposure history, requests for information on potential contacts and a physical examination by a general practitioner. Of the 14 patients, eight measles cases were identified in addition to the primary case, seven of which were confirmed in the laboratory. The mean age of the patients was 20 years (range = 19-37 years). All patients had mild disease with rash, fever or both and minimal or no conjunctivitis or Koplik spots consistent with the modified measles. There were no known complications. Two patients (A and B) were hospitalized, primarily to establish the diagnosis and provide isolation.

The patients were residents of central Israel and served on several military bases. Four patients received documentation of reception of 2 doses of measles-containing vaccine, four received 2 doses in childhood (without documentation) and the primary patient received documentation of 3 doses of MMR in Ukraine, one in 1997, 1998 and 2002. Patient A's report on receiving 2 doses of measles-containing vaccine was inconsistent with the negative IgG test result. Laboratory tests confirmed high avidity (> 60% IgG) in all patients except patient A (Table), suggesting a previous immune response (3). The epidemiological investigation identified 1.392 contacts from these nine patients. No measles cases were diagnosed among the contacts of AH patients.

Phylogenetic analysis of the viral isolates of three patients identified the B3 genotype. In conjunction with this outbreak, three measles cases with no apparent connection to military cases have been diagnosed in civilians in the Tel Aviv district. Measles B3 genotype was also identified in these cases and the sequence of the 450nt region of the N gene was identical to that of military isolates, supporting the suspicion of epidemiological link between all Israeli cases. According to GenBank, in Hungary (MG323532.1), Germany (MF593154.1) the annotated collection of all publicly available nucleotide sequences of the United States National Institute of Health, the measles virus virus B3 with the sequence of identical 450nt N gene, Belgium (MF490426.1), and Italy (KY801730.1) during the same period, reinforcing evidence that the primary case was acquired while traveling in Europe.


Public Health Response

During active search for AH patient contacts, a total of 1392 military contacts were identified and located and their doctors were notified. All contacts were instructed to seek medical attention or call IDFPHB if they developed fever or rash over the next 21 days. Contacts identified within 72 hours of exposure who had received less than 2 doses of the MMR vaccine received one MMR dose for PEP. As of August 27, a total of 162 soldiers had received PEP with MMR vaccine. Of the remaining contacts that had not been offered PEP, most had documentation of receipt of 2 doses of the vaccine containing measles; some were not identified until> 72 hours after exposure. Due to the crowded nature of the military units of two patients (A and D), vaccination of all susceptible people in the unit (ring vaccination) was performed. After consulting the Israeli Ministry of Health (MOH) with public and laboratory health specialists, and due to the low attack rate, a decision was made not to recommend a third dose of MMR for contacts. No quarantine was recommended for contacts.

As requested, IDFPHB informed MOH of the cases. Since more than 2 weeks had passed since the primary patient's air flight until the diagnosis of measles, it was not possible to administer PEP to the passengers on the flight. MOH was not informed of any Israeli measles cases in the flight contacts. Further measures taken during the outbreak were confirmation of the vaccination status of healthcare professionals in clinics and military units with confirmed cases and the issuance of a warning to military healthcare professionals regarding the outbreak.


Discussion

This measles outbreak occurred in an adult population with 2 high dose measles vaccination coverage. The primary patient had documentation of receipt of 3 doses of measles-containing vaccine, one each aged 1, 2 and 6 years, according to the Ukraine vaccination schedule. Although the registry of vaccinations may have contained an error, the high avidity of IgG suggests failure of the secondary vaccine. All but one patient had elevated measles IgG avidity, which is an indicator of previous vaccination or previous infection. Since all serum samples (except that of the primary patient) were taken 2-3 days after the onset of symptoms, the high avidity IgG was considered to be the result of previous patient vaccination.

Measles transmission from a vaccinated person with documented secondary vaccine insufficiency was also described in New York in 2011, among vaccinated healthcare providers (4) and in the Marshall Islands (10). The decline in vaccine-induced immunity is a phenomenon that needs to be addressed, especially in regions where the circulation of wild measles virus is low. Additional studies, which could include serum-epidemiological studies on the dynamics of IgG levels by age, are needed to evaluate the immunity and incidence of measles in measles in populations with high-dose vaccination coverage. Demonstrating declining immunity with age could guide the development of recommended vaccination regimens.

This outbreak highlights the importance of careful epidemiological and laboratory investigation of suspected measles cases, regardless of vaccination status, as well as the need for active contact surveillance. The symptoms reported by patients with secondary measles cases have been modified by the typical signs of fever; rash; and coryza, conjunctivitis or cough. Without active surveillance, the likelihood of measles would probably not have been considered and the circulation of the virus could have continued. Healthcare professionals should include measles in the differential diagnosis of fever and rash even in a vaccinated patient and obtain adequate laboratory tests.

The absence of tertiary cases in this outbreak is consistent with the lower transmission risk reported in other measles cases in vaccinated people, probably due to their milder symptoms, including lack or reduction of cough (4,5). In this outbreak, most of the contacts that have been completely vaccinated probably contributed to rapid containment.