Investigation and Findings

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 at a civilian hospital. Urine and serum specimens were sent to Israel’s National Measles and Rubella Laboratory (NMRL). Neither patient had traveled or had a known exposure to measles, nor was any epidemiologic link evident between the cases. Both patients had self-reported history of receipt of 2 doses of MMR vaccine. The cases in patients A and B were laboratory-confirmed serologically and by urine polymerase chain reaction (PCR) testing on August 7 and August 9, respectively (Table). A third patient with mild symptoms (patient C) was reported by NMRL staff members to IDFPHB on August 7 after urine PCR confirmation. Patient C, a soldier aged 19 years, was the partner of patient A and reported having received 2 doses of measles vaccine.

IDFPHB undertook an epidemiologic investigation to determine the source of infection, to identify contacts, and to recommend PEP. Because all three cases appeared within days of one another, a common source of infection was suspected.

Investigators learned that patients A, B, and C had visited the same crowded, mixed civilian-military clinic on July 24 during the same hour; therefore, the clinic was suspected to be the site of exposure. To evaluate that hypothesis, investigators reviewed medical records of all patients treated at the clinic on July 24 during the same time that patients A, B, and C visited. One patient examined in the clinic was a Ukraine-born soldier, aged 21 years, who was evaluated for fever and rash; measles was not suspected at the time. The investigation found that he had returned to Israel 3 days before visiting the clinic, having traveled to three European countries (France, Germany, and Ukraine) with ongoing measles outbreaks (1). Because he was suspected to be the primary patient, his serum specimen was forwarded to NMRL, where measles was serologically confirmed.

The primary patient would have been infectious from approximately 4 days before until 4 days after the onset of rash. Because more than 14 days had passed from the July 24 clinic exposure, it was anticipated that some exposed clinic contacts (in addition to patients A, B, and C) might 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 of the primary patient, were reviewed daily for the 21 days beginning July 24. The aim was to identify occurrence of fever, rash, conjunctivitis, or Koplik spots among the contacts.

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

The review of medical records led to further evaluation of 14 patients, including vaccination history, exposure history, inquiries regarding potential contacts, and a physical examination by a general practitioner. Among the 14 patients, eight measles cases were identified in addition to the primary case, seven of which were laboratory-confirmed (Table). The median patient age 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 modified measles (2). There were no known complications. Two patients (A and B) were hospitalized, primarily to establish the diagnosis and provide isolation.

Patients were residents of central Israel and served on different military bases. Four patients had documentation of receipt of 2 doses of measles-containing vaccine, four reported receiving 2 doses during childhood (with no documentation), and the primary patient had documentation of receipt of 3 doses of MMR in Ukraine, one each in 1997, 1998, and 2002. Patient A’s report of receipt of 2 doses of measles-containing vaccine was inconsistent with the negative IgG test result. Laboratory testing confirmed high avidity (>60% IgG) in all patients except patient A (Table), suggesting a previous immune response (3). The epidemiologic investigation identified 1,392 contacts of these nine patients. No measles cases were diagnosed among contacts of patients A–H.

Phylogenetic analysis of virus isolates from three patients identified B3 genotype. Concurrent with this outbreak, three measles cases with no apparent connection to the military cases were diagnosed in civilians in the Tel Aviv district. Measles genotype B3 was identified in these cases as well, and the sequence of 450nt region of the N gene was identical to that from the military isolates, supporting the suspicion of epidemiologic linkage among all Israeli cases. According to GenBank, the U.S. National Institute of Health’s open-access, annotated collection of all publicly available nucleotide sequences, measles virus B3 genotype with the identical 450nt N gene sequence was detected in Hungary (MG323532.1), Germany (MF593154.1), Belgium (MF490426.1), and Italy (KY801730.1) during the same period, strengthening the evidence that the primary case was acquired while traveling in Europe.