Herd Immunity

Herd immunity

Herd immunity is an important element in the balance between the host population and the micro-organism, and represents the degree to which the community is susceptible or not to an infectious disease as a result of members of the population having acquired active immunity from either previous infection or prophylactic immunization (see p. 731).

The effectiveness and safety of immunization programmes are monitored by observing the expected and actual effects of such programmes on disease transmission patterns in the community by appropriate epidemiological techniques.

Vaccination of boys

Herd immunity is the main driver for the proposal of universal vaccination, that is, including boys and girls. With growing evidence of the involvement of HPV in a relevant proportion of head and neck cancers, in particular oropharynx (Plummer et al., 2016), it has become clear that the burden of vaccine-preventable disease in males is not negligible (de Martel et al., 2017). The vaccine has proven to be effective also on precancerous lesions of genital mucosae in males (Palefsky et al., 2011). Nevertheless, most models still predict that the largest benefit of vaccinating boys is the indirect effect on cervical cancer in women due to the reduction of circulating virus and to establishing of herd immunity faster (Brisson et al., 2011). The opportunity and cost effectiveness of vaccinating boys is still under debate, with the extreme heterogeneity of policies adopted in industrialized countries reflecting this uncertainty.

Given the very high incidence of HPV-related cancers in males having sex with males, there is consensus that vaccinating this group is opportune (Markowitz et al., 2014; Kirby, 2015; Sauvageau and Dufour-Turbis, 2016), even though implementing effective strategies to target high-risk populations without indirectly fostering discrimination or stigmatization is challenging.

Herd immunity and indirect protection from LAIV

Herd immunity is defined as the proportion of persons with immunity in a given population,¹⁸⁰ and the indirect protection afforded by this immunity to the unimmunized segment of the population is defined as the herd effect. Herd immunity has been demonstrated for infectious diseases of viral and bacterial etiology, and it is widely accepted that this phenomenon occurs with influenza.¹⁸¹ Despite the facts that influenza vaccine policy in the United States has been focused on the immunization of persons aged 65 years and older and that vaccination rates increased from 31% to 67% between 1989 and 1997, influenza epidemics still cause widespread morbidity and mortality in this age group.^181–183

Several lines of evidence suggest that widespread immunization of otherwise healthy populations may result in interruption of transmission of influenza and thereby may indirectly protect those in high-risk groups. For example, vaccination of health care workers was associated with reduced morbidity and mortality from influenza among nursing home residents,^184–188 and health care workers now constitute a priority group for influenza vaccination in the United States.¹⁶⁹

Widespread vaccination of schoolchildren has also been proposed as a measure to reduce the burden of influenza in the community, because children are important vectors for the spread of influenza. The ability to modify the course of an influenza outbreak by vaccination of schoolchildren has been demonstrated in several studies. A vaccination rate of 86% in schoolchildren in Tecumseh, Michigan, with a monovalent inactivated vaccine, resulted in a three-fold reduction in the excess attack rate for the community from influenza compared with a neighboring community in which schoolchildren were not vaccinated.¹⁸⁹ A clear difference was observed in the rates of school absenteeism between the communities, and there was evidence that protection was not limited to children of school age. In Japan, vaccination of schoolchildren was mandatory between 1977 and 1987. In 1987, the laws were relaxed, and parents could decide whether or not their children received vaccine. In 1994, vaccination rates fell to low levels amid doubts about the effectiveness of the program. In an analysis of all-cause mortality and death attributed to influenza and of vaccination rates from Japan and from the United States between 1949 and 1998, Reichert and colleagues found that excess mortality rates, predominantly in older persons, dropped significantly in Japan with initiation of the vaccination program for schoolchildren, from rates 3 to 4 times those in the United States to rates similar to the United States.¹⁹⁰ Excess mortality rates in Japan increased with discontinuation of the vaccination program for schoolchildren.

From a practical standpoint, LAIV could be an extremely effective method to achieve herd immunity if high vaccination rates with an efficacious vaccine are achieved in schoolchildren and influenza transmission to other segments of the community is interrupted. Large numbers of children could be vaccinated in a short period of time, and intranasal administration is preferred over injection of inactivated vaccine. There is evidence from several studies that this is an effective approach. A study conducted in the 1990s demonstrated that vaccination of schoolchildren with either inactivated or Russian LAIV resulted in significant protection. In schools where the children received LAIV, vaccination rates and illness among staff and unvaccinated children were inversely correlated, suggesting reduction of transmission as a result of vaccination. Such a correlation was not seen in the schools where children received inactivated vaccine or in schools where children received placebo.¹⁹¹

There are several studies in a community in central Texas that report both direct and indirect protection against ILI afforded by vaccination of children. In these studies, age-specific rates of MAARI during the influenza season in intervention communities, where children received LAIV, were compared with rates in comparison communities, where children did not receive vaccine. Vaccination of approximately 20% to 25% of children, 1.5 to 18 years of age, in intervention communities resulted in indirect protection of 8% to 18% against MAARI in adults older than 35 years. This small effect may translate into a substantial effect at the population level. Moreover, the size of this effect may be diluted from use of clinical rather than laboratory endpoints.¹⁹² In another study, significant protection against laboratory-confirmed influenza illness and pneumonia and influenza events was observed in the children who received LAIV, but not in those who received TIV. Indirect effectiveness against MAARI was observed in 5- to 11-year-old children and in 35- to 44-year-old adults.¹⁹³ In a third study,¹⁹⁴ when schoolchildren were vaccinated with LAIV against antigenically mismatched influenza viruses, significant indirect protection from influenza was observed in all age groups, with the exception of those aged 12 to 17 years. Combined virologic surveillance and MAARI visit data suggested that a single dose of LAIV provided better protection against influenza than TIV.

King and colleagues reported a small pilot study followed by a larger, multistate, school-based immunization intervention study using LAIV.^195,196 In the pilot study,¹⁹⁵ significant (45% to 70%) relative reductions in fever or respiratory illness–related outcomes including physician visits by adults, physician visits by children, prescription or other medicines purchased by household members, and family schooldays and workdays missed, were observed for intervention ("target") school households compared with control school households. In the larger trial, intervention school households reported significantly fewer ILI-related doctor or clinic visits for children; fewer episodes of fever plus cough or sore throat in children and adults; lower ILI-related prescription, over-the-counter, and herbal medication use for ILI; lower absenteeism rates for elementary and high-school students; and fewer missed workdays for adults caring for their own ILI or for others during the peak influenza week. Relative reductions across these outcomes ranged from 25% to 40%, again confirming indirect as well as direct benefit. Limitations of this study included the lack of placebo groups and the use of questionnaires for reporting of ILI.

In summary, a large body of data demonstrates the effectiveness of vaccination of schoolchildren for the control of influenza in communities, from both direct and indirect effects of immunization. Both LAIV and TIV are highly efficacious against influenza in children, and a mechanism to explain how LAIV could afford better indirect protection is not clear. The data from these studies support the widespread vaccination of schoolchildren as a means of reducing morbidity and mortality in other high-risk members of communities.

Summary

Case Reproduction Numbers

This basic reproduction number describes the maximal spreading potential of an infection in a population. Continuing with the example in Fig. 77.3, the introduction of a single primary case into the population of T = 100,000 susceptible persons should lead to 10 secondary cases (C_t+1=100,000 × 0.0001 = 10 = R₀). Table 77.2 shows examples of numerical values of this statistic that are applicable to different infections and derived by methods described later. Fig. 77.5A is an illustration of the concept.

The same expression can also be derived just by combining Eqs. 3 and 4. As long as the proportion immune is maintained above this threshold, incidence should decrease, ultimately to the point of eradication of the infection from the population. Fig. 77.6 shows the relationship graphically, which shows the implications for persistence or decline of an infection depending on its basic reproduction number and the proportion of immune persons in the population.^1,13,16

Herd immunity

The best evidence for a herd immunity effect of IPV is the experience in the United States where IPV was introduced into routine use in 1955 and was replaced by OPV in 1962. A sharp drop in the numbers of cases of paralytic and nonparalytic polio was evident during the years 1955 to 1962 (Figure 27-5). The apparent reduction in the number of cases observed exceeded the expectation based on the percentage of children vaccinated (Figure 27-6).²¹⁴ More specific regional data were published that suggested a greater than expected reduction in polio cases.²¹⁵

The second example of herd immunity comes from the Netherlands where vaccination is refused by a religious community that is well dispersed throughout the country, although IPV is routinely administered to the rest of the population. Two outbreaks of polio have occurred in this religious group, one caused by type 1 virus in 1978 (110 cases) and the second by type 3 virus from 1992 to 1993 (71 cases). Despite the wide circulation of the virus in this community, there was only one case of polio in other Dutch communities. Approximately 400,000 unvaccinated individuals not belonging to this religious community also remained unaffected.^{216–220,270} The virulent viruses also spread to similar religious groups in North America, but cases only resulted from the 1978 outbreak.^221–223 Oostvogel et al²²⁴ did an analysis of the circulating viruses in schools affected by the outbreak from 1992 to 1993. Proof of recent type 3 infection was found in 59.5% of the unvaccinated children and in 22.2% of the vaccinated children.

The evidence for herd immunity comes from countries where oral-to-oral transmission was probably the dominant mode of interhuman poliovirus transmission. It is less clear if IPV is able to induce herd immunity in countries where the fecal-to-oral route is thought to be the primary role in transmission.

10.2 Bait density

Herd Immunity and Introduction Strategies

Protection against the bacterial meningitis pathogens through herd immunity is a remarkable, powerful, and unanticipated effect of bacterial polysaccharide-protein conjugate vaccines.³⁵ Herd immunity can account for approximately one half of their effectiveness at preventing disease and has significantly enhanced their cost-effectiveness. It is an important strategy for vaccine introduction, implementation, and evaluation. As noted, in 1999 to 2000 the meningococcal serogroup C conjugate vaccines were introduced in the United Kingdom as a broad catch-up campaign for those younger than 19 years of age, reduced nasopharyngeal carriage of serogroup C in adolescents more than 75%, and created herd immunity that has persisted for more than a decade.^413,417 The explanation for this remarkable herd immunity effect is the low R₀ (basic reproduction number, or the average number of secondary infectious cases that are produced by a single index case in completely susceptible population), estimated at 1.3, for meningococcal disease providing herd immunity with 17% to 26% vaccine coverage of the population.^35,434 In contrast, measles, mumps, pertussis, polio, and rubella have an R₀ greater than 5 and require much higher thresholds (i.e., >80% for herd immunity).⁴²⁷ The immunologic basis of mucosal (herd) immunity with conjugate vaccines remains unclear. Generation of capsule-specific mucosal immunoglobulins, transudation of high-avidity serum IgG to mucosal surfaces, and Th17-induced immunity via macrophage clearance have been proposed.³⁵

Cost-effectiveness, measured as a quality-adjusted life-year (QALY) score, is increasingly becoming an important consideration of vaccine recommendations in public health.⁴¹⁹ Using standard cost-effectiveness methods, a recent analysis estimated a routine infant meningococcal vaccination program was approximately $647,000 per QALY saved compared with the $157,000 per QALY saved with the two-dose adolescent vaccination program at the current price of $90 a dose. The ACIP concluded that routine infant meningococcal vaccination with HibMenCY was not cost-effective at this time.⁴³³