Population-level analyses often use average quantities to describe heterogeneous systems, particularly when variation does not arise from identifiable groups. A prominent example, central to our current understanding of epidemic spread, is the basic reproductive number, R(0), which is defined as the mean number of infections caused by an infected individual in a susceptible population. Population estimates of R(0) can obscure considerable individual variation in infectiousness, as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous 'superspreading events' in which certain individuals infected unusually large numbers of secondary cases. For diseases transmitted by non-sexual direct contacts, such as SARS or smallpox, individual variation is difficult to measure empirically, and thus its importance for outbreak dynamics has been unclear. Here we present an integrated theoretical and statistical analysis of the influence of individual variation in infectiousness on disease emergence. Using contact tracing data from eight directly transmitted diseases, we show that the distribution of individual infectiousness around R(0) is often highly skewed. Model predictions accounting for this variation differ sharply from average-based approaches, with disease extinction more likely and outbreaks rarer but more explosive. Using these models, we explore implications for outbreak control, showing that individual-specific control measures outperform population-wide measures. Moreover, the dramatic improvements achieved through targeted control policies emphasize the need to identify predictive correlates of higher infectiousness. Our findings indicate that superspreading is a normal feature of disease spread, and to frame ongoing discussion we propose a rigorous definition for superspreading events and a method to predict their frequency.

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Superspreading and the effect of individual variation on disease emergence

An outbreak of measles in 1985-86 in a community where measles vaccine trials had been carried out from 1974-76 allowed the assessment of the role of secondary vaccine failures in previously immunized children. A total of 188 children from the vaccine trial were followed. Of these, 175 seroconverted initially while 13 (6 per cent) required re-immunization (primary failure). A total of 13 cases of measles, eight of which were laboratory and/or physician-confirmed, were reported in this cohort. Of these, nine cases occurred in the 175 subjects who had hemagglutination inhibition test (HI) and neutralizing antibody responses following the initial immunization. These nine cases represent secondary vaccine failures. An additional four cases occurred in the 13 subjects with primary vaccine failure. We conclude that secondary vaccine failures occur and that while primary failures account for most cases, secondary vaccine failures contribute to the occurrence of measles cases in an epidemic. A booster dose of measles vaccine may be necessary to reduce susceptibility to a sufficiently low level to allow the goal of measles elimination to be achieved.

https://ajph.aphapublications.org/doi/pdfplus/10.2105/AJPH.79.4.475

The role of secondary vaccine failures in measles outbreaks.

A prolonged school-based outbreak of measles provided an opportunity to study "vaccine-modified" mild measles and secondary vaccine failure. Thirty-six (97%) of 37 unvaccinated patients had rash illnesses that met the Centers for Disease Control clinical case definition of measles, but 29 (15%) of 198 vaccinated patients did not, primarily because of low-grade or absent fever. Of 122 patients with seroconfirmed measles, 10 patients (all previously vaccinated) had no detectable measles-specific IgM and significantly milder illness than either vaccinated or unvaccinated patients with IgM-positive serum. Of 108 vaccinated patients with seroconfirmed measles, 17 patients (16%) had IgM-negative serology or rash illnesses that failed to meet the clinical case definition; their mean age (13 years), age at the time of vaccination, and time since vaccination did not differ from those of other vaccinated patients. The occurrence of secondary vaccine failure and vaccine-modified measles does not appear to be a major impediment to measles control in the United States but may lead to underreporting of measles cases and result in overestimation of vaccine efficacy in highly vaccinated populations. ( JAMA . 1990;263:2467-2471)

Mild Measles and Secondary Vaccine Failure During a Sustained Outbreak in a Highly Vaccinated Population

Since the licensing of measles vaccine in 1963, the incidence of reported measles in the United States has declined to less than 2 percent of previous levels. To characterize the current epidemiology of measles in the United States, we analyzed measles outbreaks that occurred during 1985 and 1986. There were 152 outbreaks (defined as five or more cases related epidemiologically), which accounted for 88 percent of the cases reported during those two years. There were two major types of outbreaks: those in which most of the cases occurred among preschool-age children (those under 5 years of age) (26 percent) and those in which most of the cases occurred among school-age persons (those 5 to 19 years of age) (67 percent). The outbreaks among preschool-age children ranged in size from 5 to 945 cases (median, 13); a median of only 14 percent of the cases occurred in vaccinated persons, and a median of 45 percent of the cases were classified as preventable according to the current strategy. Outbreaks am...

Patterns of transmission in measles outbreaks in the United States, 1985-1986.

Background Information on measles vaccine effectiveness (VE) is critical to help inform policies for future global measles control goals. Methods We reviewed results of VE studies published during 1960-2010. Results Seventy papers with 135 VE point estimates were identified. For a single dose of vaccine administered at 9-11 months of age and ≥12 months, the median VE was 77.0% (interquartile range [IQR], 62%-91%) and 92.0% (IQR, 86%-96%), respectively. When analysis was restricted to include only point estimates for which vaccination history was verified and cases were laboratory confirmed, the median VE was 84.0% (IQR, 72.0%-95.0%) and 92.5% (IQR, 84.8%-97.0%) when vaccine was received at 9-11 and ≥12 months, respectively. Published VE vary by World Health Organization region, with generally lower estimates in countries belonging to the African and SouthEast Asian Regions. For 2 doses of measles-containing vaccine, compared with no vaccination, the median VE was 94.1% (IQR, 88.3%-98.3%). Conclusions The VE of the first dose of measles-containing vaccine administered at 9-11 months was lower than what would be expected from serologic evaluations but was higher than expected when administered at ≥12 months. The median VE increased in a subset of articles in which classification bias was reduced through verified vaccination history and laboratory confirmation. In general, 2 doses of measles-containing vaccine provided excellent protection against measles.

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Field Effectiveness of Live Attenuated Measles-Containing Vaccines: A Review of Published Literature

An outbreak of measles occurred in a high school with a documented vaccination level of 98 per cent. Nineteen (70 per cent) of the cases were students who had histories of measles vaccination at 12 months of age or older and are therefore considered vaccine failures. Persons who were unimmunized or immunized at less than 12 months of age had substantially higher attack rates compared to those immunized on or after 12 months of age. Vaccine failures among apparently adequately vaccinated individuals were sources of infection for at least 48 per cent of the cases in the outbreak. There was no evidence to suggest that waning immunity was a contributing factor among the vaccine failures. Close contact with cases of measles in the high school, source or provider of vaccine, sharing common activities or classes with cases, and verification of the vaccination history were not significant risk factors in the outbreak. The outbreak subsided spontaneously after four generations of illness in the school and demonstrates that when measles is introduced in a highly vaccinated population, vaccine failures may play some role in transmission but that such transmission is not usually sustained.

M Baltier

Papers

Measles outbreak in a vaccinated school population: epidemiology, chains of transmission and the role of vaccine failures