Abstract

From 1997 to 2001, sequence data from 55 clinical specimens were obtained from confirmed measles cases in the United States, representing 21 outbreaks and 34 sporadic cases. Sequence analysis indicated the presence of 11 of the recognized genotypes. The most common genotypes detected were genotype D6, usually identified from imported cases from Europe, and genotype D5, associated with importations from Japan. A number of viruses belonging to genotype D4 were imported from India and Pakistan. Overall, viral genotypes were determined for 13 chains of transmission with an unknown source of virus, and seven different genotypes were identified. Therefore, the diversity of Measles virus genotypes observed in the United States from 1997 to 2001 reflected multiple imported sources of virus and indicated that no strain of measles is endemic in the United States.

Introduction

An important component of laboratory surveillance for measles is the genetic characterization of wild-type viruses.^[1] This genetic information provides a powerful adjunct to standard epidemiologic data for describing the transmission pathways of Measles virus (MeV). Molecular epidemiology supports classical epidemiology in cases for which the source of imported MeV is known by confirming that the viral genotype obtained is consistent with the genotype known to be circulating in the country or region from which the case was imported. Molecular epidemiology fills in the gaps of information when classical epidemiology fails to discover the source of MeV, by providing a likely source on the basis of the genotypic information.

Monitoring the pattern of measles genotypes in an area can help document the effectiveness of control measures. For example, in areas that have endemic transmission of measles, virologic surveillance of cases detects a limited number of genotypes. On the other hand, in areas where endemic transmission of virus has been interrupted, a variety of genotypes are detected, reflecting the multiple sources of imported viruses. Virologic surveillance has already been used to help document the interruption of transmission of measles in the United States^[2-4] and Australia.^[5] In addition, genetic analysis of viruses provides a means to differentiate vaccine-associated cases of measles from cases caused by infection with wild-type virus. Current surveillance protocols call for the collection of appropriate specimens for virologic surveillance during all phases of measles control. For countries such as the United States that are in the elimination phase of measles control, the goal is to collect a specimen for viral isolation along with a serum sample at first contact with each suspected case.

Genetic characterization of wild-type MeV is based on sequence analysis of two variable regions on the viral genome. The targets for molecular epidemiologic studies are the 450 nucleotides coding for the 150 amino acids comprising the COOH-terminus of the nucleoprotein and the entire protein-coding region of the hemagglutinin gene. Based on these sequences, a number of genotypes have been identified.^[2,3,5-18] The World Health Organization (WHO) recognizes 20 genotypes and one proposed genotype,^[19-21] including several new genotypes that have been identified in the last 3 years.^{[14,15,21-23]} The prototype (Edmonston) strain of measles as well as all the currently used measles vaccines are in genotype A.^[21]

The purpose of this report is to describe the genetic characteristics of wild-type measles viruses isolated in the United States during 1997-2001. Overall, the results show a pattern consistent with the continued interruption of endemic transmission. Viruses representing several of the recently described genotypes were associated with imported cases in the United States, and this information has increased our understanding of the degree of genetic diversity in wild-type measles viruses.