Measles is a highly infectious viral infection that is a leading cause of death because of vaccine preventable diseases worldwide. Although an effective measles vaccine was licensed in 1963,1,2 3–5 surveillance activities. In October 1997, Member States in the Eastern Mediterranean Regional Office of the World Health Organization (WHO) adopted a resolution for elimination of measles from the region by 2010.6
Measles and rubella are important public health problems in Iran. In the early 1980s, the country experienced regular outbreaks of measles with 30,000–50,000 case reports annually. Despite achieving high sustained coverage with 2 doses of measles vaccine, Iran continued to experience high rates of disease throughout the 1990s. In 2002, the Ministry of Health and Medical Education (MOHME) outlined a plan for measles elimination that included conducting a nationwide measles immunization campaign using a combined measles and rubella vaccine for all persons 5–25 years of age.7
METHODS
Review of Epidemiology of Measles in Iran.
We reviewed vaccination coverage and measles surveillance data from 1980 to 2005. Vaccination coverage data in Iran are collected on a monthly basis from all provinces. This “doses administered” is summarized on an annual basis and compared with estimated number of surviving infants for the same year. Surveillance for measles and rubella is the responsibility of the Centers for Disease Control in Iran (CDC-Iran) and is managed by a network of Universities that are responsible for collecting surveillance data and forwarding this information to CDC-Iran. The CDC-Iran uses the WHO case definitions for measles and rubella and established a policy for serologic testing of all suspect patients using enzyme immunoassays (Dade Behring AG Enzygnost) for IgM antibody to measles and rubella after the nationwide vaccination campaign. Before the campaign, rubella surveillance was not well established and there was limited information on disease burden in Iran.
Review of Data From Nationwide Campaign.
We reviewed results of a nationwide measles vaccination campaign. The campaign was conducted at ∼23,000 fixed vaccination sites including primary health care units, rural and urban health centers, as well as private and university hospitals. To supplement immunization activities at fixed centers, approximately 9000 mobile teams were trained to provide vaccine in outreach settings including schools, universities, military campuses, and factories. Each team consisted of 3 persons including a vaccinator, 1 physician or nurse, and 1 person for registering patients and vaccination data. Vaccination activities were monitored through the use of tally sheets of vaccine doses administered at the district and provincial levels. Data were entered into a computerized database at the provincial level medical universities and sent to the CDC-Iran on a daily basis. These data were reviewed to calculate vaccination coverage.
Postcampaign Serosurvey.
From March 5 through March 12, 2004, a postcampaign serosurvey was performed using multistage cluster sampling methods. The country was divided into high, medium, and low risk districts based on a measles epidemiologic profile, and a sample 10 districts was selected from each group using probability of selection being proportional to the size of the district population. The epidemiologic profile of districts was developed using vaccination coverage and disease surveillance information.
In each district, 3 clusters of 55 individuals were sampled including 2 clusters in urban areas and 1 in rural areas. The study was reviewed and approved by a committee for the protection of human subjects in Iran and informed consent was obtained from all persons who agreed to participate in the survey. Serum samples were collected and processed on the day of collection and stored at −20°C until serologic testing was conducted using commercially available ELISA kits (Dade Behring) for lgG antibody to measles virus. Antibody response was classified as positive, borderline, or negative for both measles and rubella.
RESULTS
Evolution of Measles Elimination Strategy.
The national measles vaccination program was officially initiated in 1967 and was supported by a local manufacturer (Razi Institute) that produced monovalent measles vaccine containing 1000 CCID50 of Sugiyama strain. Between 1967 and 1983, vaccination services were formally established in Iran, however measles vaccination was not routinely offered in the public sector. After establishment of the Expanded Program on Immunization (EPI) program in 1984, measles vaccine was offered to all infants at 9 months of age, and vaccination coverage increased rapidly to levels >90% in 1992 (Fig. 1 ). A second dose of measles (MCV2) at the age of 15 months was added to the EPI schedule in 1984.
FIGURE 1.:
Meases Incidence and Vaccination Coverage*, 1985–2006, MOHME Iran. ―――――Measles incidence, −MCV1 coverage, ―-―MCV2 coverage.
Despite reaching high vaccination coverage with both doses of vaccine, the incidence of measles remained high in the early 1990s and a subnational measles campaign was planned for 1995. During this campaign, 6.6 million children 9 months to 15 years of age in “high risk” districts were vaccinated. This campaign had limited impact on disease incidence and the MOHME revisited their immunization strategy in 2002. After recommendations of the National Advisory Committee on Immunization Practices, the MOHME planned a nationwide immunization campaign targeting all persons 9 months to 24 years of age in 2003. After the campaign, the vaccination schedule was changed with the first dose being given at 12 months and the second dose at school-entry.
Surveillance for Measles.Surveillance for measles in Iran was implemented in 1966 and strengthened with the beginning of EPI program in 1983. Before 2004, ∼10% of patients with suspect measles had serologic testing. Several measles outbreaks were reported in 2001–2002 with the largest proportion of disease occurring among persons 15–25 years of age (37% in 2001, 42% in 2002). In the year before the campaign, there were 9734 case reports of patients with measles including 1137 patients with serologically confirmed disease (Fig. 2 ).
FIGURE 2.:
Measles cases before mass campaign (2002) compared with confirmed measles after the campaign (2006).
After the campaign, CDC-Iran developed guideline and provided training on case-based surveillance for measles including in-depth case investigation and laboratory testing for all suspect measles patients. From January 2004 through November 2006, the MOHME evaluated 749–850 suspect cases per year (∼1.2 suspect per 100,000); 62% of suspect cases had serologic testing (Table 1 ). A high proportion (30%) of patients without testing were children <1 year of age. The surveillance system identified 3 patients with laboratory-confirmed measles in 2004, 7 in 2005 and 45 in 2006 resulting in an incidence of <1 case per 1 million population. Genotyping of measles virus isolates has identified D4 as the circulating genotype before and after the campaign.
TABLE 1:
Most of the patients with measles resided in areas close to neighboring countries where measles outbreaks are common (Fig. 2 ). Among the 45 patients identified in 2006, 9 were classified as imported cases, 27 indigenous, and 9 where the source of infection remained unknown. There have been no clusters of >10 measles cases and no episodes of sustained measles virus transmission after detection of a confirmed case. Since 2004, 41 patients with rubella have been identified. Rubella was not included in the surveillance system before 2004.
Campaign Coverage.
In December 2003, the MOHME conducted a nationwide mass immunization campaign during a 1 month period including 21 days for vaccination and 1 week for mopping up activities. All persons age 5–25 years old were targeted to receive 1 dose of MR vaccine regardless of previous immunization status or history of measles or rubella. The target age group was selected based on the age distribution of disease and plans for changes in the EPI schedule. Approximately 80% of case-reports before the campaign occurred among persons 5–25 years of age. Children <5 years of age were not included in the campaign because they would receive a second dose of measles vaccine on school entry between 2004 and 2008.
To ensure a high quality campaign, special efforts and planning were conducted in the following areas: social mobilization, briefing of community leaders, quality and quantity of vaccine, adequate logistics for receipt, storage and distribution of vaccines and syringes, training of staff, ensuring safe injections, responding to potential adverse effects, and disposal of injection materials. Campaign coverage was calculated by dividing the number of doses administered by the target population.
The campaign was completed during a 1 month period; 32,706,498 Iranian nationals and 872,484 non-Iranians were vaccinated. There was no difference in vaccination status by age group, gender, or geographic location. A total of 199,383 individuals declined vaccination including 108,714 pregnant women and 90,669 persons who had other contraindication for vaccination. After adjusting data for persons with contraindications, vaccination coverage exceeded the expected target of 33,579,082 persons.
Postcampaign Serosurvey.
The results of the postcampaign serosurvey showed that antimeasles and antirubella antibodies were positive in 97.4% and 94.6% of person, respectively. The prevalence of antibody was lower among children 1–5 years of age (Table 2 ). Among age cohorts who were targeted during the campaign, there was no difference in the prevalence of antimeasles and antirubella antibodies by age, gender, and district of residence.
TABLE 2:
DISCUSSION
This report suggests that Iran has achieved substantial progress in achieving measles and rubella elimination. Demonstrating measles elimination is challenging because of complex data requirements and the need for sustained monitoring. Key criteria for elimination include the following: (1) high population-based immunity, (2) low disease incidence, (3) absence of endemic strains and sustained transmission after importation of disease, and (4) a surveillance system that is sensitive enough to detect low levels of disease transmission.
Routine vaccination coverage data, coverage data from the mass campaign and results from the postcampaign serosurvey all indicate that high population-based immunity has been achieved in Iran. The only age cohorts identified with >5% susceptibility to measles were children <5 years of age. These children were not targeted for the campaign because they would receive a second dose of measles at school-entry. Maintaining high coverage with the first and second doses of measles-mumps-rubella (MMR) is a high priority for the Ministry of Health.
Surveillance for measles is challenging in Iran where there are considerable logistic challenges to conducting laboratory-based surveillance in areas with difficult access and where providers are reluctant to conduct serologic testing on patients <12 months of age. Member States in the Eastern Mediterranean Region (EMR) of the WHO have adopted a background rate of >2 suspect cases per 100,000 population as indicator of surveillance sensitivity to detect measles transmission in a highly vaccinated population based on the global experience with measles surveillance .8 surveillance indicators including serologic testing on >90% of suspect case-patients and completeness of epidemiologic investigations. It is challenging to get providers to adhere to these recommendations in Iran. To improve the rate of testing of suspect cases, the MOHME plans to use saliva-based assays for children <1 year of age. Currently, the surveillance system is detecting 1.2 suspect cases per 100,000 which is slightly below the benchmark set in Eastern Mediterranean Regional Office. Efforts are being made to improve the sensitivity of reporting and it remains to be seen whether the sensitivity indicator can be met.
Most of the patients with confirmed measles since the campaign reside in communities with migrant populations that travel to neighboring countries having a high disease incidence. There have been no episodes of sustained measles virus transmission in these communities and no clusters of measles with >10 patients. One constraint of the current surveillance system is the limited information on circulating genotypes before and after the mass campaign. Iran has only recently developed capacity for measles virus isolation and characterization. Efforts are now underway, to isolate virus from measles patients and it is anticipated this will greatly assist in monitoring chains of transmission and help characterize endemic versus imported disease.
The sensitivity of the surveillance system, coupled with the low incidence of confirmed disease (<1 case per million) and lack of transmission after detection of a confirmed case support the conclusion that Iran has achieved measles elimination. Although maintaining high population immunity can interrupt measles virus transmission,9 10–12 Surveillance data will be monitored to whether a follow-up campaign is needed in due course.
The EMR has established a goal to eliminate the incidence of congenital rubella syndrome among countries that have introduced rubella vaccine. Criteria to document CRS elimination have not been established and establishing a surveillance system to detect CRS is complex. Although the definitions of these issues continue to be debated at the regional and global level, the MOHME plans to focus efforts on detecting acute rubella. If outbreaks occur, then CRS surveillance will be addressed.
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