Control of a community outbreak of measles which started in a poorly immunised high school population

Abstract: An outbreak of measles occurred in Darwin from February to March 1991. The first case was in a 13-year-old high school student who had returned from a holiday overseas. She was symptomatic on the second day of the new school term. She infected an infant while both waited in a doctor's surgery. Outbreak control measures were instituted 18 days later when the Communicable Diseases Centre was first alerted of cases through the laboratory notification scheme. Through active surveillance, we identified 76 cases of measles, of whom 92 per cent (70 cases) were under 20 years of age. Of these, 46 were students at the index high school in which the attack rate was 39.2 per 1000. They transmitted the disease to six unvaccinated siblings aged 11 to 18 years, resulting in a secondary attack rate of 113 per 1000 in this age group (relative risk of disease in siblings 2.8, 95 per cent confidence interval 1.2 to 6.2). The outbreak affected one other high school, a number of primary schools, one tertiary institution, and nine children under five years. Only four of the cases had a verified history of previous immunisation against measles. The outbreak was arrested within two weeks of instituting community-wide control measures. Inadequate immunisation coverage among school-aged children and delays in notification contributed to the severity of the outbreak. Improved measles surveillance systems, including telephone notification of clinical cases are needed so that control measures can be instituted immediately within the household and in the community.     

Epidemiological and molecular assessment of a measles outbreak in a highly vaccinated population of northeast Italy

Two distinct measles outbreaks, unrelated from the epidemiological point of view but caused by genetically related strains, occurred in the Friuli Venezia Giulia region of northeastern Italy. Forty-two cases were reported during the period April-May 2008. In the first outbreak the index case was a teacher who introduced the virus into the Pordenone area, involving eight adolescents and young adults. The other concomitant outbreak occurred in the city of Trieste with 33 cases. The containment of the epidemics can be explained by the high MMR vaccine coverage in an area where the first dose was delivered to 93·4% and the second dose to 88·3% of the target children. Phylogenetic analysis of 14 measles virus strains showed that they belonged to a unique D4 genotype indistinguishable from the MVs/Enfield.GBR/14.07 strain, probably introduced from areas (i.e. Piedmont and Germany) where this genotype was present or had recently caused a large epidemic.     

An explosive point-source measles outbreak in a highly vaccinated population. Modes of transmission and risk factors for disease

In 1985, 69 secondary cases, all in one generation, occurred in an Illinois high school after exposure to a vigorously coughing index case. The school's 1,873 students had a pre-outbreak vaccination level of 99.7% by school records. The authors studied the mode of transmission and the risk factors for disease in this unusual outbreak. There were no school assemblies and little or no air recirculation during the schooldays that exposure occurred. Contact interviews were completed with 58 secondary cases (84%); only 11 secondary cases (19%) of these may have had exposure to the index case in the classrooms, buses, or out of school. With the use of the Reed-Frost epidemic model, only 22-65% of the secondary cases were likely to have had at least one person-to-person contact with the index case during class exchanges, suggesting that this mode of transmission alone could not explain this outbreak. A comparison of the first 45 cases and 90 matched controls suggested that cases were less likely than controls to have provider-verifiable school vaccination records (odds ratio (OR) = 8.1) and more likely to have been vaccinated at less than age 12 months (OR = 8.6) or at age 12-14 months (OR = 7.0). Despite high vaccination levels, explosive measles outbreaks may occur in secondary schools due to 1) airborne measles transmission, 2) high contact rates, 3) inaccurate school vaccination records, or 4) inadequate immunity from vaccinations at younger ages.     

Cost-benefit analyses of supplementary measles immunisation in the highly immunized population of New Zealand

As endemic measles is eliminated from countries through increased immunisation, the economic benefits of enhanced immunisation programs may come into question. New Zealand has suffered from outbreaks after measles introductions from abroad and we use it as a model system to understand the benefits of catch up immunisation in highly immunised populations. We provide cost-benefit analyses for measles supplementary immunisation in New Zealand. We model outbreaks based on estimates of the basic reproduction number in the vaccinated population (R_v, the number of secondary infections in a partially immunised population), based on the number of immunologically-naïve people at district and national levels, considering both pre- and post-catch up vaccination scenarios. Our analyses suggest that measles R_v often includes or exceeds one (0.18–3.92) despite high levels of population immunity. We calculate the cost of the first 187 confirmed and probable measles cases in 2014 to be over NZ$1 million (∼US$864,200) due to earnings lost, case management and hospitalization costs. The benefit-cost ratio analyses suggest additional vaccination beyond routine childhood immunisation is economically efficient. Supplemental vaccination-related costs are required to exceed approximately US$66 to US$1877 per person, depending on different scenarios, before supplemental vaccination is economically inefficient. Thus, our analysis suggests additional immunisation beyond childhood programs to target naïve individuals is economically beneficial even when childhood immunisation rates are high.     

Mumps outbreak in a highly vaccinated school population: assessment of secondary vaccine failure using IgG avidity measurements

From March to April 2006, an outbreak of mumps occurred in Gyeonggi, Korea. The aim of this study was to describe and discriminate between primary and secondary vaccine failure in a highly vaccinated population for mumps using IgG avidity testing. Fifteen clinical mumps cases occurred among 41 students. Among these 15 patients, 11 vaccinated patients were considered secondary vaccine failures with high IgG titers and a high avidity index (AI, > or =32%); an unvaccinated patient was considered to have primary infection with high IgG titers and low AI, and three vaccinated patients were considered as other infections with low IgG titers and low AI. Among 26 unaffected students, 5 vaccinated patients were retrospectively diagnosed as sub-clinical infection with high IgG titers and high AI; the remaining students had low IgG titers and low AI except for one previously infected student. The results of this study show that secondary vaccine failure played an important role in this mumps outbreak. Therefore, booster immunization for mumps should be considered in immunized adolescents to prevent further outbreaks.     

Measles vaccine efficacy during an outbreak in a highly vaccinated population: incremental increase in protection with age at vaccination up to 18 months.

During a large measles outbreak in Quebec City in 1989, two investigations conducted in parallel evaluated the relative risk of measles and measles vaccine effectiveness with respect to age at vaccination. The study was a school-based case-control study including 563 cases and 1126 classmate controls. The second was a cohort study of the siblings of school cases including 493 siblings aged between 1 and 19 years. The relative risks (RR) of measles were similar in both settings and the trend towards increased vaccine efficacy with increasing age at vaccination was highly significant (P < 0.001). Vaccine efficacy rose from 85% in children vaccinated at 12 months of age to > or = 94% in those vaccinated at 15 months and older. Even for children vaccinated at or after 18 months of age, the RR of measles was reduced when compared with children vaccinated between 15 and 17 months of age (RR 0.61, CI 95% 0.33-1.15). Small changes in the timing of initial measles vaccination can have a major impact on vaccine efficacy.     

An evaluation of measles, mumps and rubella vaccine in a population of Yorkshire infants

In October 1988 combined measles, mumps and rubella (MMR) vaccination replaced monocomponent measles as part of the routine childhood vaccination programme in the United Kingdom. Prior to this policy change a study was undertaken in 335 children aged 15 months, to evaluate the clinical reactions and immunogenicity of the new combined MMR vaccine (Trimovax, Immravax, Merieux), in comparison with an established monocomponent measles vaccine (Rouvax, Merieux). Parents were asked to select whether their child should receive MMR vaccine or measles monocomponent; over 95% chose MMR. Children who were given the MMR vaccine had seroconversion rates of 96% for measles, 97% for mumps and 100% for rubella, whilst those who received monocomponent measles vaccine had a seroconversion rate of 100%. The number of side effects reported was similar with both vaccines; all were mild and self-limiting. The results from this study confirm the efficacy and low reactogenicity of MMR vaccine and support its use as part of the routine childhood immunisation programme in the United Kingdom.     

Introduction of measles into a highly immunised West African community: the role of health care institutions.

In an urban area of Guinea-Bissau, where more than 80% of the children have been vaccinated, measles continues to be a major cause of child mortality. Compared with the period before the introduction of vaccination, more cases occur outside the community, while more cases within the district are now guests and newcomers. Half of the new introductions of measles into the community and 30% of the measles deaths can be traced back to the paediatric ward. Contact with health care institutions plays an important role in the transmission of measles, particularly among the youngest children. This consequence of health care may be avoidable, however, since several studies suggest that sick children can be vaccinated safely and effectively.     

Field evaluation of measles vaccine efficacy in Mozambique

Monitoring measles vaccine efficacy is an important form of quality control in immunization programs. Retrospective cohort studies of vaccine efficacy were conducted in Mozambique with the aim of adopting this method for regular use. The authors studied 1,215 and 790 children aged 12-35 months in the cities of Nampula and Beira, respectively. In Nampula (1985), vaccine efficacy was estimated to be 40%, and in Beira (1986), it was estimated to be 59%. To investigate the possibility of falsely low results due to poor specificity of maternal reporting of measles cases, a seroepidemiologic study of 600 children aged 12-47 months was conducted in Nampula in 1986. The specificity and sensitivity of a maternal history of measles in an unvaccinated child were estimated as 83% and 56%, respectively. These results were used to obtain an adjusted vaccine efficacy estimate of 66%, almost double the estimate of 37% obtained using data on history of vaccination and illness alone. The large bias introduced into the vaccine efficacy estimation by low specificity of disease diagnosis is a serious limitation to the use of retrospective cohort methods to assess efficacy.     

Estimation of the time-dependent vaccine efficacy from a measles epidemic

We present a method to estimate the time-dependent vaccine efficacy from the cohort-specific vaccination coverage and from data on the vaccination status of cases and apply it to a measles epidemic in Germany which involved 529 cases, 88 of whom were vaccinated and 370 unvaccinated (for the remaining 71 cases the vaccination status is unknown). Our epidemiological model takes into account that maternal antibodies prevent successful vaccination and that vaccine immunity may be lost over time. Model parameters are estimated from the data using maximum likelihood. Vaccination coverage, as determined in school surveys, ranged from 27.6 per cent for the cohort born in 1974 to 85 per cent for the 1986 cohort, which is far too low to prevent measles transmission. Cohorts for which no school surveys were performed are omitted from analysis. Thus, sufficient data are available for only 282 cases, 69 of whom are vaccinated. According to our estimates, measles vaccinations provided no immunity before 1978 (95 per cent CI: 0 to 47 percent), for the period 1978-1982, the estimated vaccine efficacy was 80 percent (95 percent CI: 67 to 89 percent), and for 1982-1990 it was 97 percent (95 percent CI: 93 to 99 percent). After 1990, the estimated value dropped to 89 per cent, but its confidence interval widely overlaps with that of the previous period (95 percent CI: 74 to 97 percent). Loss of immunity was estimated to be zero (95 percent CI: 0 to 0.003/year). Several sensitivity analyses were performed with respect to the model assumptions. A modified model which assumed constant efficacy at all vaccination times yielded a high estimate of 96 per cent (95 percent CI: 92 to 98 percent) for primary vaccine efficacy but also a high loss rate of immunity of 0.007/year (95 percent CI: 0.001 to 0.012) to explain the high fraction of vaccinated cases among older individuals. The likelihood score value is however significantly inferior compared to the score value of the model with time-dependent vaccine efficacy.     

Cost of a measles outbreak in a remote island economy: 2014 Federated States of Micronesia measles outbreak

After 20 years with no reported measles cases, on May 15, 2014 the Centers for Disease Control and Prevention (CDC) was notified of two cases testing positive for measles-specific immunoglobulin M (IgM) antibodies in the Federated States of Micronesia (FSM). Under the Compact of Free Association, FSM receives immunization funding and technical support from the United States (US) domestic vaccination program managed by the Centers for Disease Control and Prevention (CDC). In a collaborative effort, public health officials and volunteers from FSM and the US government worked to respond and contain the measles outbreak through an emergency mass vaccination campaign, contact tracing, and other outbreak investigation activities. Contributions were also made by United Nations Children’s Emergency Fund (UNICEF) and World Health Organization (WHO). Total costs incurred as a result of the outbreak were nearly $4,000,000; approximately $10,000 per case. Direct medical costs (≈$141,000) were incurred in the treatment of those individuals infected, as well as lost productivity of the infected and informal caregivers (≈$250,000) and costs to contain the outbreak (≈$3.5 million). We assessed the economic burden of the 2014 measles outbreak to FSM, as well as the economic responsibilities of the US. Although the US paid the majority of total costs of the outbreak (≈67%), examining each country’s costs relative to their respective economy illustrates a far greater burden to FSM. We demonstrate that while FSM was heavily assisted by the US in responding to the 2014 Measles Outbreak, the outbreak significantly impacted their economy. FSM’s economic burden from the outbreak is approximately equivalent to their entire 2016 Fiscal Year budget dedicated to education.     

An outbreak of measles in a rural Queensland town in 1997; an opportunity to assess vaccine effectiveness.

This report describes a measles outbreak in a rural town in south-east Queensland and presents the results of a vaccine effectiveness (VE) study performed during this outbreak. It is important to assess the effectiveness of a vaccine in an outbreak to determine if the outbreak is due to failure of the vaccine or failure to vaccinate. There were 44 cases of measles amongst local residents, which represents a notification rate of 396.7 per 100,000 population. Case investigations identified a group of people who had been exposed to measles at a seminar. The attack rate for the seminar cohort was 18% (11/61). This presented an opportunity to conduct a VE study using data about children aged less than 16 years who attended the seminar. In this cohort of 23 attendees, all 7 children who had not received any measles vaccinations became cases whilst the 6 who were fully vaccinated for their age according to NHMRC guidelines were protected from measles illness. Although there were insufficient fully vaccinated cohort members to reliably estimate VE for this group, the vaccine was 84.6% (95% CI: 15.0-99.7%) effective for those who had received at least one validated dose of vaccine. Despite the sample size limitations, the results support the view that failure to vaccinate rather than vaccine failure contributed to the high infection rate in the seminar cohort.     

The efficacy of whole cell pertussis immunisation: collected data on a vaccine produced in France

The place of whole cell pertussis vaccines in paediatric immunisation schedules is under re-evaluation by public health authorities in many countries, with the expectation that the newly licensed acellular Bordetella pertussis vaccines will induce fewer adverse events while providing equivalent efficacy. In France, for instance, the CSHPF (Conseil supérieur d'hygiène public de France) recently modified its long-standing recommendation that French children only receive whole cell pertussis vaccine. Consequently, an acellular pertussis vaccine may be used for the first booster, at 16-18 months of age, and should be used for the reinforcing dose at 11-13 y of age. French children, nonetheless, continue to receive whole cell pertussis vaccine for the primary series immunisations at 2, 3, and 4 months, as the only whole cell pertussis vaccine available in France (licensed by Aventis Pasteur) has a long-established record of safety and protective efficacy. A review of its unpublished and published clinical results, obtained from studies throughout the world, demonstrates an efficacy of from 84-100% in six different retrospective analyses or outbreak investigations and a protective efficacy of 92% by clinical trial.     

An outbreak of influenza B at an Indiana boarding school: estimate of vaccine efficacy

During the influenza season of 1979–80, influenza B accounted for most cases of influenza in the United States. The midwestern States experienced widespread influenza B activity beginning in mid-December. From late January to mid-February an outbreak of influenza-like illness occurred at a private boarding school for boys in northeastern Indiana. Most of these boys had been vaccinated against influenza. An influenza B virus was isolated in 1 instance, and 5 of the 24 boys from whom acute- and convalescent-phase serum specimens were obtained showed evidence of influenza B infection.Through a questionnaire survey, it was determined that 18 percent of the boys had had an influenza-like illness; the attack rate was 39 percent for the unvaccinated and 14 percent for the fully vaccinated. The vaccine efficacy was thus estimated to be 63 percent. As was true of many of the influenza B viruses isolated in the 1979–80 influenza season, the virus isolated at the school demonstrated some variation from the B/Hong Kong/5/72 virus used in the vaccine.