European Journal of Epidemiology 16: 601±606, 2000. Ó 2000 Kluwer Academic Publishers. Printed in the Netherlands.
Herd immunity and herd eect: new insights and de®nitions
T. Jacob John1 & Reuben Samuel1,2 1Department of Clinical Virology, Christian Medical College Hospital; 2Department of Community Health, Christian Medical College, Vellore, Tamil Nadu, India
Accepted in revised form 21 April 2000
``Words are not only vehicles to convey ideas but also their drivers.'' Anon.
Abstract. The term herd immunity has been used by a population in which an immunisation programme is various authors to conform to dierent de®nitions. instituted. Herd immunity applies to immunisation or Earlier this situation had been identi®ed but not cor- infection, human to human transmitted or otherwise. rected. We propose that it should have precise meaning On the other hand, herd eect applies to immunisation for which purpose a new de®nition is oered: ``the or other health interventions which reduce the proba- proportion of subjects with immunity in a given pop- bility of transmission, con®ned to infections trans- ulation''. This de®nition dissociates herd immunity mitted human to human, directly or via vector. The from the indirect protection observed in the unim- induced herd immunity of a given vaccine exhibits munised segment of a population in which a large geographic variation as it depends upon coverage and proportion is immunised, for which the term `herd ecacy of the vaccine, both of which can vary geo- eect' is proposed. It is de®ned as: ``the reduction of graphically. Herd eect is determined by herd immu- infection or disease in the unimmunised segment as a nity as well as the force of transmission of the result of immunising a proportion of the population''. corresponding infection. Clear understanding of these Herd immunity can be measured by testing a sample of phenomena and their relationships will help improve the population for the presence of the chosen immune the design of eective and ecient immunisation parameter. Herd eect can be measured by quantifying programmes aimed at control, elimination or eradi- the decline in incidence in the unimmunised segment of cation of vaccine preventable infectious diseases.
Introduction (1) ``Herd immunity. The resistance of a group to attack by a disease because of the immunity of a large The term `herd immunity' is increasingly frequently proportion of the members and the consequent less- seen in recent literature on the epidemiology of in- ening of the likelihood of an aected individual fectious diseases and on their prevention and control coming into contact with a susceptible individual'' [1]. by immunisation. This was found by Medline search (2) ``Herd immunity. It is not necessary to immu- (1992±1998) using the key words `herd immunity' and nise every person in order to stop transmission of an `herd eect'. While a large number of papers were infectious agent through a population. For those found with the key word `herd immunity', none was organisms dependent upon person-to-person trans- found with the key word `herd eect'. A review of mission, there may be a de®nable prevalence of im- several papers has shown that `herd immunity' is used munity in the population above which it becomes by dierent authors for dierent ideas, such as a dicult for the organism to circulate and reach new concept, a phenomenon or a measurable parameter. susceptibles. This prevalence is called herd immunity'' In this paper we oer new insights and suggest a new [2]. de®nition of the term `herd immunity' and dissociate (3) ``Herd immunity. It is well known that not it from the indirect eect of immunisation of part of a everyone in a population needs to be immunised to population on the incidence of infection or disease in eliminate disease ± often referred to as herd immu- the unimmunised remainder, for which the term `herd nity. This is because successful immunisation re- eect' is proposed and de®ned. duces the number of susceptibles in the population and this eectively reduces the eciency with which De®nitions currently available for herd immunity the microbe is transmitted from one person to the other. This has the same eect on the incidence of Three de®nitions of herd immunity given in recent infection as a reduction in the number of individuals text or reference books are quoted below. The em- in a population. The microbe cannot sustain itself phasis of phrases is ours. and disease disappears at some level of vaccine 602 coverage that is less than 100%. On the other hand, and additional annual repetitive vaccination of the coverage below that needed to prevent disease may same cohorts of susceptible children were necessary have little impact on the total number of suscepti- for 8±9 years to interrupt transmission in Brazil, bles ± as has been predicted using mathematical showing that `herd immunity' was not evident for models and veri®ed, in the case of rubella, by ob- the same vaccine against the same disease, but in a servation. The implementation of immunisation dierent region [5]. This clearly shows that herd programmes needs to be accompanied by case sur- immunity (by the third de®nition) is a function of veillance, in conjunction with analysis of appropri- not only immunisation but also the force of trans- ate serological samples both before and after the mission of the pathogen. This de®nition is ambigu- introduction of the vaccine. If such data are not ous about one aspect of the end point: is it zero carefully scrutinised, the consequence may be dire. disease or infection? The second de®nition clearly For example, an immunisation programme may re- addresses infection while the ®rst one focuses on duce the number of cases but at the same time may infection and disease. Only the second de®nition increase the average age at which the infection oc- clari®es that we are dealing with only person-to- curs. If the severity of disease increases with age of person transmitted infectious diseases. acquisition, as in rubella (the risk of an infected A new insight in the third de®nition is that in some foetus in an infected woman) and polio (the risk of cases it might be harmful to immunise a proportion paralytic disease), an immunisation programme may and obtain only partial or incomplete `herd immu- be less useful than none at all'' [3]. nity', since it might worsen the problem by delaying The ®rst de®nition considers herd immunity con- infection and not eliminating it, as in the case of ceptually as the resistance to disease due to reduced maternal and foetal rubella [2]. This is an important risk of infection in a group of individuals as a result point. A similar situation might arise in the cases of of a large proportion among them (but not all) being immunisation against hepatitis A and varicella also. immune, not necessarily due only to immunisation Partial coverage of children may slow down virus [1]. The second de®nition clari®es that the term ap- circulation and delay infection in the unimmunised. plies to the actual proportion of immunised indi- Hepatitis A and varicella are more severe in adults viduals necessary to make it dicult for the than in children. Here a new phrase such as `partial' organism to circulate and reach new susceptibles [2]. or `incomplete' herd immunity had to be introduced By this de®nition herd immunity is a threshold value to overcome the problem caused by the very de®ni- of a measurable parameter (vaccination coverage) tion which demands disappearance of disease. resulting in retardation of person-to-person trans- A review of several recent publications with the key mission of an infection. Elimination of infection or word herd immunity showed that the term has most disease is not required but only implied in this def- often been used to mean the concept of reduced inition. How can we arrive at a de®nable level transmission due to high immunisation level, in ac- (proportion) of immunity when the end point is cordance with one or another of the three de®nitions merely diculty of transmission, which is not de- given above. For example the `concept of herd im- ®ned, hence not measurable? The third de®nition is munity' has been advocated as useful in designing closely similar to the ®rst but it develops it further to immunisation programmes. [6, 7]. Herd immunity has a phenomenon providing the means to eliminate an been quali®ed as a `key concept' in population based infectious disease from a population when a pro- immunisation programmes [7]. The author of a portion that is less than 100% is immunised [3]. Here landmark review of the history, theory and practical the phenomenon has a measurable end point ± that aspects of herd immunity chose not to prefer ``any of the disappearance or elimination of disease in a single de®nition of herd immunity, rather accepting group. In contrast to the second de®nition, here the the varied uses of the term by dierent authors'' [8]. actual input (immunisation coverage) necessary to Recognising the consequent potential for confusion, achieve this measurable endpoint can be quanti®ed. the reviewer coined the phrase `herd immunity However it seems that the term herd immunity refers threshold' to indicate the minimum prevalence of to the phenomenon of zero incidence in the unim- immune individuals necessary to interrupt trans- munised segment rather than the actual proportion mission of infection [8]. Its major purpose was to immunised to achieve it [3]. The strict application of distinguish between the desirable outcome of inter- this de®nition requires the disappearance of disease ruption of transmission from the potentially unde- due to immunisation coverage of less than 100% of sirable eect mentioned above. In general herd susceptibles. This is a very rare event, exempli®ed by immunity is considered desirable by most authors, the global eradication of smallpox without immun- but there is incongruity in using the term `immunity' ising all susceptibles and the elimination of polio- to cover adverse outcomes also. In summary, the myelitis due to wild polioviruses form North de®nitions are not clear, precise or complete; nor do America when only some 65 to 70% immunisation they agree among themselves. A precise de®nition is coverage had been reached [4]. Interestingly, in the necessary. We do not favour the status quo approach case of poliomyelitis, near 100% coverage of infants adopted by one reviewer [8]. 603
The proposed new de®nition for herd immunity ent term, namely `herd eect' is introduced to denote the perturbation, if any, on the incidence of disease or The term herd immunity contains two words, herd infection in the unimmunised segment of a popula- (meaning a group or community) and immunity tion, induced by the herd immunity of immunisation. which has to be interpreted. Previously the term im- munity did mean a state of protection but today it means a state in which the immune system of the The proposed de®nition of herd eect body has reacted speci®cally to de®ned immuno- gen(s). It is an attribute of the individual, not a It is proposed that herd eect be de®ned as the al- group. If so desired immunity can be tested for, as the teration of the epidemiological frequency parameters presence of antibody, or as skin test or lymphocyte (of infection or disease as the case may be) in the response to stimulation, against the chosen antigen. unimmunised segment of a population as a result of Putting the two terms together, it is proposed that immunising a proportion of the population. The al- herd immunity be now de®ned simply as the pro- teration is usually a decline of incidence of infection portion of subjects with immunity in a given popu- (hence lower incidence of disease). Therefore it may lation. Under this de®nition herd immunity is be simpler to de®ne it as the reduction of infection or quanti®able by testing a sample of the population for disease in the unimmunised segment as a result of the presence of the selected immune parameter. It immunising a proportion of the population. Lowered may be due to natural infection, or immunisation, or incidence of infection due to the herd eect of im- a combination of both. It is not dependent on the munisation may, in some cases, be associated with ease or diculty of circulation of an infectious agent, increased incidence of disease consequent upon an nor its elimination. In certain cases, past infection upward shift in age of infection (example hepatitis A, (inducing long lasting immunity) and immunisation maternal rubella syndrome in infants) or increased (inducing near 100% immunity which is long lasting) severity disease (such as adult varicella). However, in may be used as surrogates of immunity for quanti- the age group immunised there will always be a re- fying herd immunity. duction of incidence if there was herd eect. In most, Indeed, some authors have actually used the term if not all other cases, herd eect of high herd immu- herd immunity to mean the proportion of subjects nity induced by immunisation is bene®cial in reducing with immunity, in conformity with our new de®nition the burden of disease; its extreme bene®t is the in- and clearly at variance with the de®nitions cited terruption of transmission itself. In some earlier earlier [9±11]. They have obviously assumed that they publications by one of us, the term herd eect had were using the term correctly [9±11]. For example, in actually been used with this meaning [12, 13]. a survey of antibody prevalence by age to varicella- Earlier we had drawn attention to the contrast zoster virus, the prevalence was referred to as herd between North America where polioviruses were immunity [9]. In a study of measles outbreaks in two eliminated with routine immunisation coverage (with adjacent towns in Japan, the term `herd immunity 3 doses of oral poliovaccine) of below 80% and South level' was used interchangeably with the sum of fre- America where near 100% coverage with some 9±10 quency of vaccination and of previous history of doses were required for the same eect [5]. According measles [10]. The authors presented it as the com- to the new de®nitions the herd immunity and the herd plement of `susceptibility rate' [10]. In another study eect were dierent in these two regions. The reason of antibody prevalence and hepatitis A outbreaks, the for dissimilar herd immunity is the geographic dif- former was equated to herd immunity [11]. There are ference in vaccine ecacy, necessitating a higher level many more such publications in which the term herd of vaccine coverage in the region with lower vaccine immunity has been used in accordance with our new ecacy to achieve a similar level of herd immunity. de®nition. The large dierence in the vaccine coverage and To recapture the spirit of the earlier but imprecise number of doses needed to eliminate polioviruses in de®nitions, we can say that as herd immunity due to South America in comparison to North America immunisation increases, at some point, which is short cannot be attributed to the lower herd immunity of 100% coverage, the circulation of the corre- alone but to insucient herd eect as well. The dif- sponding agent may cease. That point or value of ference in herd eect for similar levels of herd herd immunity (called `herd immunity threshold' by immunity is due to dierence in the force of trans- one author) cannot be the same for dierent diseases mission of wild polioviruses [12, 13]. In other words, and for the same diseases it need not be the same in when 100 children are given three doses, whereas in dierent communities [8]. An interesting question North America virtually 100% herd immunity is in- could be asked: can the consequence (short of elimi- duced, in South America and in India only some 70% nation of infection) of increasing herd immunity by is induced, proving lower vaccine ecacy [12, 13]. immunisation be measured? If it can be, then the Whereas the median age of poliomyelitis (in the pre- ®xation on the requirement of interruption of trans- immunisation era) in North America was above mission can be eliminated. For this purpose a dier- 15 years, it was below 15 months in India, proving 604 higher force of transmission [12, 13]. The confound- protection'. Interestingly they measured this eect as: ing of the assumed direct relationship between vac- (Indirect protection) = (1 ) R), where R was the cine coverage and incidence of infection by these two ratio of incidence rates in contacts (parents and sib- phenomena (dissimilar herd immunity for similar lings) of recipients of toxoid (immunised) and of vaccine coverage and dissimilar herd eect for similar placebo (unimmunised) [14]. This parallels the herd immunity) confused many world experts on method of measurements of vaccine ecacy, polio, who persisted with the three-dose dogma (until (VE) = (1 ) R), where R is the ratio of the incidence about 1990), mainly because of the lack of clear rates in immunised and unimmunised. Therefore, de®nition of the term herd immunity and the lack of for ease of use, we may use the term `VE equivalent' understanding of the relationships between herd im- for the measure of herd eect, since the method munity, herd eect and transmission of polioviruses. of measurement and the way it is expressed as the As an aside, the enhanced potency inactivated po- percent reduction in incidence are both very much liovaccine does not show any geographic variation of like VE itself. vaccine ecacy. We have observed much better herd It now becomes obvious that herd eect confounds eect of the latter vaccine; this is additional evidence the measurements of VE, since the incidence in the for our argument presented above [12, 13], In short, unimmunised is altered by the introduction of im- when herd immunity is rede®ned to mean the im- munisation in a group. Thus, the measurement of VE munity prevalence in a population, the cessation of subsumes herd eect when it is estimated in `®eld' transmission due to immunisation can be seen as the (community) immunisation programme settings. An herd eect of high herd immunity due to high im- interesting corollary of this relationship between herd munisation coverage with a vaccine having high eect and VE is that in a community in which im- vaccine ecacy. munisation has already been introduced the true VE Since herd eect is not necessarily break in trans- cannot be measured by comparing the incidences in mission, but the reduction in transmission, a lower the vaccinated and the unvaccinated; the measured coverage level would have a lower herd eect and a VE will be an underestimate. In such situations either very high coverage level could result in high herd historical data on incidence prior to introducing eect leading to zero incidence even in the unim- vaccination or incidence in an unvaccinated but munised. While herd immunity is applicable to any similar community must be used to obtain the true infection irrespective of its transmission pathways measure of VE, corrected for herd eect. If VE is and to immunity induced naturally (by infection) or measured in a clinical study, in which a limited arti®cially (by immunisation), herd eect applies only number of children living in a large community are when infected persons participate in the transmission immunised, implying thereby that herd eect is min- of an agent and when immunisation induces at least imum or none, then we may get a dierent value. If some protection against infection (and not merely the immune response of immunised children is mea- against disease). Thus, immunisation against tetanus sured in the clinical setting, then we get only a sur- or rabies (even if given routinely) will have no herd rogate for VE without exhibiting protection, and not eect. As BCG inoculation seems to protect only confounded by herd eect. For these reasons, the against progressive primary tuberculosis and not term vaccine ecacy should be quali®ed as `immu- against secondary type pulmonary tuberculosis, it nogenic VE,' `clinical VE' and `®eld level VE' as has also has no herd eect. already been suggested [12].
The measurement of herd eect Relevance of herd eect and herd immunity in immunisation programmes To be useful in understanding and quantifying the eects of immunisation it is not sucient to dier- From the de®nitions of and relationships between entiate herd eect from herd immunity, but we herd eect and herd immunity stated above it is clear should be able to measure them. It was pointed out that neither is relevant for the vaccination of an oc- earlier that herd immunity is measurable by testing a casional individual, but both are important elements sample of the population for the required parameter in large scale or community wide immunisation pro- of immunity. Under certain circumstances, herd eect grammes. Programme managers are advised to factor can also be measured. One of the best studies in in these issues in planning an immunisation pro- which it was measured is that of immunisation of gramme, or when introducing a new vaccine in an children with pertussis toxoid decreasing the spread existing programme, and also to monitor herd im- of pertussis within the family [14]. The investigators munity and herd eect in the community as part of found that vaccination of children with the toxoid planned assessment/evaluation. The relationship be- was followed by signi®cant reduction in incidence of tween the two will depend on the type of immunity in pertussis among siblings and parents. They did consideration, its realised value at a point in time and not use the term herd eect, but called it `indirect the rate at which it is realised. Immunising agents 605 which provide protection only against disease but not pulmonary tuberculosis in the hope that further against infection may have no herd eect. Many spread may be curtailed. This is another example of vaccines protect well against disease but not so well `indirect protection' not due to immunity but due to against infection. Since infection without disease is decreased chance of spread, very much like in the case silent, it would seem that the protection is against of reduced transmission due to immunisation. If in- infection also. Partial protection against infection creasing proportions of persons with pulmonary may result in lower extent of multiplication or shorter tuberculosis are diagnosed and treated early, the in- duration of potential transmissibility, thereby tending cidence of infection in the susceptible population to reduce the risk of infection in others. The level of should continue to decline; this may also be called herd eect induced by a vaccine (providing at least herd eect. On the other hand, if multi-drug therapy some protection against infection) will depend on the of leprosy should have similar herd eect, we must be level of herd immunity at a point in time, probably in sure that transmission occurs from the infected per- a non-linear fashion and this would further be mod- sons directly (like tuberculosis) or via vector (like i®ed by the rate at which this level is achieved in ®lariasis). The lack of conclusive evidence for such relation to time. For example, we have shown that transmission is a lacuna in the strategy to control the herd eect achieved in `pulse immunisation' is leprosy taking advantage of the assumed herd eect very much higher than that of routine immunisation of multi-drug therapy. In the case of malaria, programme, for the same level of herd immunity [12, chemoprophylaxis in a large proportion of persons 13, 15]. In our pioneering experiment, with 65% and/or the use of insecticide-impregnated bed nets coverage with 3 doses of OPV given in pulse fashion, may also have some herd eect. This is due to the fact the transmission of poliovirus appeared to have that each prevented infection reduces further trans- ceased abruptly, in contrast to its continued circula- mission and also because mosquitoes may not get tion in spite of over 90% coverage in year round access to infected persons sleeping in nets. routine immunisation [15]. Even though this dier- Thus herd eect may in general be de®ned as the ence may be partly due to the short duration of gut change (reduction) in the incidence of infection or immunity induced by OPV, the principle of excellent disease in the un-intervened segment of a susceptible herd eect of pulse immunisation is still valid as has population due to the intervention in the rest of the been shown with successful elimination of measles population, compared to the incidence in the absence from a community by annual single day pulse im- of intervention in the entire population. However, we munisation of only children over one year [16]. have focused on the herd eect of immunisation Investigation, clear conceptualisation and applica- programmes in this paper and we recommend that tion of these relationships will improve our ability to the term be quali®ed by the nature of intervention design eective and ecient immunisation pro- when appropriate (as due to early diagnosis and grammes aimed at control, elimination or eradication treatment, mass treatment etc). In ordinary use, when of vaccine preventable infectious diseases in the trans- not quali®ed, herd eect will be taken as due to herd mission of which humans participate signi®cantly. immunity.
Herd eect of interventions other than vaccination References
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