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Understanding Herd immunity
 

Understanding Herd immunity

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  • ``Words are not only vehicles to convey ideas but also their drivers.''Anon.the concept of reduced transmission due to high immunisation level,The definitions are not clear, precise or completeThe term herd immunity contains two words, herd (meaning a group or community) and immunity which has to be interpreted. Previously the term immunity did mean a state of protection but today it means a state in which the immune system of the body has reacted speci®cally to de®nedimmunogen(s).
  • Michael Bröker ”Indirect effects by meningococcal vaccines:Herd protection vs. herd immunity” Human Vaccines 7:8, 881-882; August 2011. neutral umbrella term “herd effect” may be used
  • Most of the earlier theoretical work is based on the simple ‘herd immunity threshold’ concept assuming that vaccines induce solid immunity against infection in a randomly mixing populationAccording to this concept, the key determinants of herd immunity are based on the basic reproduction number, R0 (the average number of other individuals each infected individual will infect in a population that has no immunity to the disease). In order to eliminate or eradicate an infection, the proportion of immune individuals in a population (as can be achieved by critical vaccine coverage) must be equal to or greater than (1–1/R0)Imagine a situation in which a person acquires an infection and then migrates to a population in which the infectious agent hasnever previously circulated, and thus all in the population are susceptible to infection
  • Imagine a situation in which a person acquires an infection and then migrates to a population in which the infectious agent hasnever previously circulated, and thus all in the population are susceptible to infectionDuring the period of infectiousness an infectious person has contact with 4 other persons and with 2 of the 4 the contact is “close” enough for the infection to be transmitted.
  • he or she infects 2 others (first generation) and then these 2 others each go on to infect a further 2 others of their 4 contacts (second generation
  • these 2 others each go on to infect a further 2 others of their 4 contacts (second generation
  • Now consider the same situation after half of the population has been rendered immune to infection by vaccination, so that (on average)2 out each person’s 4 contacts will be not-susceptible to infection
  • When the initial infectious person is introduced into the population only one infection results (first generation) as one of the contacts who previously would have been infected has been protected by vaccination. Similarly, the 1 newly infected person only goes on to infect 1 person (second generation) because half of the contacts have been directly protected by vaccination.In this situation the effective reproductive number (sometimes designated by “R”) is thus 1.This is because the person was indirectly protected, as the person who would have infected them was themselves protected by vaccination and therefore did not pass the infection on. This is an illustration of a herd-protective effect of vaccination,
  • where increasing the level of vaccination (in this case from zero to 50%) has reduced the risk of infection among the unvaccinated. Thus, in scenario (A) the attack rate among susceptibles in the second generation was 25% whereas in scenario (B) it is 12.5%
  • In order for an infection which is transmitted from person to person, or for which humans are the principal reservoir, to be maintained in a population, each case of infection must give rise to at least one other case – i.e. the effective reproduction number must be above 1. If the effective reproduction number is below 1 then the infection will eventually die out in the population. That is, if the herd protective effect reduces the risk of infection among the uninfected sufficiently then the infection will no longer be sustainable within the population and the infection will be eliminatedIn general, the effective reproductive number (R) will be lower than the basic reproductive number (R0), depending on the proportion (P) of the population who are immune to infection. Such immunity may be induced either by a previous infection with the agent (if such infection produced immunity) and/or by immunisation with an effective vaccine. Simply, R = (1-P) * R0.Therefore, for infection elimination or eradication – i.e. to reduce R below 1, then P must be equal to at least (1-1/R0). So, for example, if R0 = 5 then P must be at least (1-1/5) = 0.8. That is, 80% of the population must be immune, either through previous infection or vaccination.The value of P that reduces R to at most 1 is commonly called the “herd immunity threshold” – the level of population immunitythat is necessary for the infection to be no longer self-sustaining in the population
  • Simple threshold concept of herd immunity. A, Relationship between the herd immunity threshold, (R0 – 1)/R0 = 1 - 1/R0,and basicreproduction number, R0, in a randomly mixing homogeneous population. Note the implications of ranges of R0, which can vary considerably between populations [12], for ranges of immunity coverage required to exceed the threshold. B, Cumulative lifetime incidence of infection in unvaccinated individuals as a function of the level of random vaccine coverage of an entire population, as predicted by a simple susceptible-infected-recovered model for a ubiquitous infection with R0 = 3 [13]. This assumes a 100% effective vaccine (E 5 1). Note that the expected cumulative incidence is 0 if coverage is maintained above VC = 1- 1/R0 = 67%
  • The national immunization coverage of all antigens in the regular NIP program in 2067/68 has improved compared to last fiscal years. However, the coverage is not uniform throughout the country. Thirty‐one districts (41%) have >90 percent coverage for all antigens. There has been 97percent coverage for BCG, 95 percent for Polio‐3, 96 percent for DPT‐Hep B‐Hib 3, 88 percent for Measles and 41 percent for TT‐2 to pregnant women. BCG vs Measles dropout rate increased from 8.6 percent in 2066/67 to 9.8 percent in 2067/68. The vaccine wastage rate for DPT‐HepB‐Hib is 8.6 percent which is higher than the recommended wastage rate of five percent (single dose vial) and for OPV it is 23.4 percent which is higher than the recommended wastage rate of 15 percent.School Immunization programme has been continued. Two rounds of National Immunization Program and Intensified National Immunisation Days (NIDs) have substantially contributed towards the goal of eliminating polio.The objectives of the National Immunization Program are as follows:• Achieve and sustain 90 percent coverage of DPT3 by and of all antigens• Maintain polio free status• Sustain MNT elimination status• Initiate measles elimination• Expand vaccine preventable disease (VPDs) surveillance• Accelerate control of other vaccine preventable diseases through introduction of new vaccines• Improve and sustain immunization quality• Expand immunization services beyond infancy
  • R0 may vary between different populations and in different segments, or at different times, in the samepopulation, as discussed above. Thus the to estimate, required herd immunity threshold for infection elimination is more complex that the simple formula given aboveR0 may also vary from population to population depending on factors such as population density, which may affect the number of effective contacts a person has while they are infectious
  • Thus, immunisation against tetanusor rabies (even if given routinely) will have no herde€ect. As BCG inoculation seems to protect onlyagainst progressive primary tuberculosis and notagainst secondary type pulmonary tuberculosis, italso has no herd e€ect.
  • increased incidence of disease consequent upon an upward shift in age of infection (example hepatitis A, maternal rubella syndrome in infants) or increased severity disease (such as adult varicella).
  • A 23-valent polysaccharide vaccineherd effect is, if anything, poor, but there is strong evidence of protection against invasive pneumococcal disease (IPD)It was estimated that the total burden of pneumococcal pneumonia prevented by infant PCV7 vaccination in the USA from 2000 to 2006 involved a reduction of approximately 800 000 hospitalizations from pneumococcal pneumonia; 90% of this was attributed to herd immunity in adults aged 18 years or older; a similar reduction in mortality was also attributed to the vaccine [
  • Meningococcal polysaccharide vaccines have been in use since the 1970s; however, there is only limited evidence of protection offeredby these vaccines against carriageOn the contrary, meningococcal conjugate vaccines prime the immune system for persistent immunologic memory and have impact on nasopharyngeal carriage
  • Two live attenuated vaccines against rotavirus infectionare known to be well tolerated and effectivein children: Rotarix (GlaxoSmithKline, Rixensart, Belgium) is a monovalent vaccine containing human rotavirus G1P1 [8] strain RotaTeq (Merck, Whitehouse Station, NJ, USA) is a pentavalent vaccine containing five human–bovine rotavirus reassortants with human serotypes G1, G2, G3, G4 and P1 [8] and the bovine serotypes G6 and P7.
  • high risk for complications of influenza, including the elderly, pregnant women, young children, and individuals with chronic diseasesA trivalent inactivated influenza vaccine, a cold adapted live attenuated influenza vaccine (LAIVthat assessed whether vaccinating school-aged children with inactivated influenza vaccine could prevent influenza in other family and community membersvaccinating high-risk populations is unlikely to reduce the burden of seasonal epidemics, because these groups represent only a fraction of thepopulation among whom the virus spreads [25]. In addition, the attack rates in these groups are relatively lowAnother challenge with only vaccinating high-risk groups is that the vaccines may not work as well in these at-risk populations. The efficacy of the influenza vaccine is dependent on the immunological status of the specifi c population being vaccinated and on the type of vaccine
  • The protective effectiveness in non-recipients of study vaccine was 61% (95% CI 0.08 – 0.83; p 0.03) for reducing laboratory-confi rmed infl uenza (3.1% in unvaccinated adults of vaccinated colonies vs 7.6% in unvaccinated colonies; ARR 40.0 per 1000, NNT 25.0 persons;
  • vaccination has been implemented in many countries including USA, Canada, Uruguay, several European countries, Australia and some Asiancountries.The effect of varicella vaccination was evaluated in Uruguay 6 years after implementation of vaccination. Compared with the prevaccination years, there was a more than 80% reduction in varicella hospitalizations in children [32]. In addition to the substantial reduction in the age group that were eligible for vaccination, large decreases were also observed in other age groups suggesting herd effects of the vaccine
  • Since the introduction of the measles, mumps and rubella vaccine in the UK in 1988, vaccine uptake was maintained well above 90% until 1998 when rates started falling, down to less than 80% by 2003 because of the ‘autism rumor’
  • To control lymphatic filariasis, mass treatment with Ivermectin or diethyl carbamazine is being used in many endemic areas. By reducing the parasitaemia in individuals and reducing the number of parasitaemic individuals, the drug causes a reduction in transmission to susceptibles even if they had not taken the drug. Mass application of the drug is akin to pulse application of a vaccine. If done well, filariasis could be eliminated by this approach since there is no extra-human source of infection. Even though 100% of population do not (and need not) receive treatment, the reduction of infection in the untreated segment is the herd effect of pulse therapy with the drug.If increasing proportions of persons with pulmonary tuberculosis are diagnosed and treated early, the incidence of infection in the susceptible population should continue to declineIn the case of malaria, chemoprophylaxis in a large proportion of persons and/or the use of insecticide-impregnated bed nets may also have some herd effect. This is due to the fact that each prevented infection reduces further transmission and also because mosquitoes may not getaccess to infected persons sleeping in nets
  • Fine et al has addressed the complexities of imperfect immunity, heterogeneous populations, nonrandom vaccination, and‘‘freeloaders’’Imperfect ImmunityIf vaccination does not confer solid immunity against infection to all recipients, the threshold level of vaccination required to protect a population increases If vaccination protects only a proportion E among those vaccinated (E standing for effectiveness against infection transmission, in the field), then the critical vaccination coverage level should be Vc=(1-1/R0)/E. We can see from this that if E is<(1 - 1/R0) it would be impossible to eliminate an infection even by vaccinating the whole population. Similarly, waning vaccine-induced immunity demands higher levels of coverage or regular booster vaccination.Important among illustrations of this principle are the shifts to multiple doses (up to 20) and to monovalent vaccines in the effort to eliminate polio in India, where the standard trivalent oral polio vaccines and regimens produce low levels of protection
  • Heterogeneous Populations-Nonrandom MixingIn the concepts of herd immunity threshold, It is assumed that transmission of infection occurs in randomly mixed homogenous population. However in the field, there is heterogeneity in transmission arising from age related factor genetics factor, spatial and behavior factor.Although the mathematics to describe heterogeneous mixing are complex, the critical threshold remains: Vc = (1 - 1/R0)/E, except that R0 is no longer a simple function of the average number of contacts of individuals. Instead, R0 is a measure of the average number of secondary cases generated by a ‘‘typical’’ infectious personThis average depends on how the various groups interact and can be calculated from a matrix describing how infection spreads within and between groups. Interactions are often observed to be more frequent within than between groups [24], in which case the most highly connected groups will dominate transmission, resulting in a higher value of R0, and a larger vaccination threshold than would be obtained by assumingthat all individuals display average behaviorin a heterogeneous population, the ‘R0’ in the formula should also account for the factors that affect the interaction of various groups in a population. Groups that are highly interconnected will dominate transmission resulting in a higher value of R0, and thus requiring a larger vaccination threshold
  • If vaccination coverage differs between groups in a population, and these groups differ in their risk behavior, the simple resultsno longer follow.To illustrate this, consider a population consisting of 2 groups, high and low risk, and suppose that each high-risk case infects 5 high-risk individuals and each low-risk case infects 1 low-risk individual. Here, R0 5 5, so Vc 5 80%.Because the high-risk group is responsible for any increase in incidence, outbreaks could in theory be prevented by vaccinating 80% of the high-risk group alone, thus ,80% of the entire population.In general, if highly transmitting groups can be preferentially vaccinated, lower values of coverage than predicted using random vaccination models can suffice to protect the entire populationIf those at greatest risk are the least likely to be vaccinated—perhaps because both are associated with poor socioeconomic conditions—extra resources are required to ensure sufficient coverage in the disadvantaged communitiesSocial clustering among parents who decide not to vaccinate their children can result in groups of children in which vaccination levels are well below the herd immunity threshold [27]. The same effect is found in religious communities that eschew vaccination though they form only a small proportion of the population, the fact that they often mix selectively with other members of the same community means that they are at an elevated risk of infection
  • when coverage is close to Vc , or when vaccination is perceived to carry a risk similar to or greater than the infection, the incentive for a logical individual to receive a vaccine is lowered [32]. One observes this in the declining measles and pertussis vaccine coverage in several countries with low disease incidence, after media scares about vaccines.It is not surprising that a sustained low incidence of infection, caused in large part by successful vaccination programs, makes the maintenance of high vaccination levels difficult, especially in the face of questioning or negative media attention.‘freeloaders’ – people who wish that everyone else around them is vaccinated except themselves – create a special scenario. They take the advantage of herd immunity without taking the trouble of getting the vaccine. If immunity wanes over time, as in the case of pertussis or measles, there is a risk of focal outbreaks around the freeloaders

Understanding Herd immunity Understanding Herd immunity Presentation Transcript

  • Dr Dipesh Tamrakar 1st yr JR SPH & CM
  • Content  Definition  Basic concepts  Beneficial and Deleterious effect  Example  Recent concepts
  • Herd Immunity  Oxford Text book of public health “ It is the relative protection of a population group achieved by reducing or breaking the chains of transmission of an infectious agent because most of the population is resistant to infection through immunization or prior natural infection”
  • Definition contd…  Harrision principle of internal medicine `` Successful vaccination protects immunized individuals from infection, thereby decreasing the percentage of susceptible persons within a population and reducing the possibility of infection transmission to others. At a definable prevalence of immunity, an infectious organism can no longer circulate freely among the remaining susceptibles. This indirect protection of unvaccinated (nonimmune) persons is called the herd immunity effect”
  • Herd Immunity and Herd Effect  Herd Immunity:``the proportion of subjects with immunity in a given population.”  Herd Effect:``the reduction of infection or disease in the unimmunized segment as a result of immunising a proportion of the population'' T. Jacob John & Reuben Samuel
  • Herd Immunity Vs Herd Protection  Herd protection: Protection to the unimmunized individual without inducing immunity, virtually by breaking the transmission of the infection or lessening the chances of susceptible coming in contact with infective individual  Herd immunity: Immunity to the unimmunized individual by secondary spread of the attenuated viruses or bacteria in the vaccine when shed in fecal matter. Yash Paul
  • 1. Herd immunity and Herd protection—oral poliovirus vaccine (OPV), oral typhoid, and oral rotavirus. 2. Herd protection only— inactivated poliovirus vaccine (IPV), diphtheria, pertussis, measles, mumps, rubella, varicella, pneumococcal, meningococcal, hepatitis A, hepatitis B, typhoid (other than oral). 3. Do not provide any additional benefit to the unimmunized—tetanus, rabies, and Japanese encephalitis. Yash paul
  • Concepts Behind Herd Immunity
  • Contd…
  • Contd…
  • Basic Reproductive Number  The basic reproductive number (R0) is the average number an infectious person will infect with an agent in a completely susceptible population. Peter G Smith
  • Contd… Peter G Smith
  • Contd… Peter G Smith
  • Contd… Peter G Smith
  • Contd… Peter G Smith
  • Peter G Smith
  • Herd immunity threshold: Basic concepts  In order for an infection, to be maintained in a      population, each case of infection must give rise to at least one other case. The “effective reproduction number” (R) has to be reduced below 1. If a proportion P of the population are immune then R = (1- P) R0 So, to get R down to about 1, P must be up to 1-1/ R0 Thus if R0 = 5 then vaccine coverage will have to be in excess of 80% The value of P that reduces R to at most 1 is commonly called the “herd immunity threshold” Peter G Smith
  • Fine et al
  • (Approximate) Herd Immunity Thresholds for Infection Elimination Peter G Smith
  • Basic Reproductive Number  R0 will vary from agent to agent depending on the infectiousness of the agent – e.g. -how long it survives in the environment - the dose necessary for infection - the duration of infectiousness in the host -Whether or not infectiousness precedes infection symptoms  R0 may vary between different populations and in different segments, or at different times, in the same population
  • Transmission dynamics of an infectious agent and Herd immunity  Infections for which herd immunity may be important in reducing the risk of infection in non-immunes in the population are those : – which are transmitted directly from person to person (e.g. measles, rubella, varicella) – for which humans are the reservoir, or an important reservoir of infection (e.g. polio, malaria)  There may be no herd protection if human are not an important reservoir of infection (e.g. tetanus, rabies
  •  Beneficial effects • Potential for infection elimination • Reduced risk of infection for those refusing vaccination (“free riders”) • Reduced risk of infection for those for who vaccination is contraindicated (e.g.immunosuppressed)
  •  Deleterious effects • Raise the average age of infection among those who are infected – Particular problem for those infections where the severity of infection increases with age (e.g. polio, rubella, mumps varicella, measles, hepatitis A)
  • Example
  • Pneumococcal vaccine  A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced to the routine childhood immunization in the USA in 2000. Evidence suggests that the elderly have indirectly benefited considerably from this introduction of conjugate vaccine in US children.  Example :comparing prevaccination and postvaccination eras, showed that cases of IPD, IPD deaths and hospitalizations related to pneumonia all decreased substantially with a 54% reduction in nonbacteremic pneumococcal pneumonia among adults 65 years of age or older
  • Meningococcal  In Canada, following introduction of a meningococcal C vaccine program in infants and adolescents under 20 years of age, a trend of decreasing serogroup C incidence was also observed among individuals aged20 years or older [incidence rate ratio (IRR) per year 0.84, 95% confidence interval (CI) 0.74–0.95]; incidence decreased by 16% per year, on average, despite the fact that this group was not the target of the province’s conjugate C program
  • Rota virus  Austria was the first European country to implement universal mass vaccination against RVGE for all infants nationwide  Epidemiological data from a hospital-based surveillance system in Austria show that incidence rates of children hospitalized with RVGE decreased in 2009 compared with 2008 and compared with the prevaccination period 2001– 2005.  Decreasing hospitalization rates from RVGE were observed in children of all age groups, even in those not eligible for vaccination according to their age, suggesting either a secular trend and/or herd immunity induced by universal mass vaccination against RVGE
  • influenza  a cluster randomized trial among Hutterite colonies in Canada : found that the rate of PCR-confirmed influenza was significantly lower in the ‘influenza vaccine’ colonies compared with the control colonies with an overall protective effectiveness against influenza of about 60% in contacts of influenza vaccinated children, suggesting a substantial herd effect of the vaccine  In a recent US trial involving school children aged 4–11 years, herd protection attributed to LAIV was detected for essentially all age groups despite a vaccine mismatch
  • Varicella  the Australian vaccination strategy targeted children aged 18 months together with a catch-up campaign for children aged 10–13 years of age with no history of prior varicella infection or vaccination  An Australian study, comparing the incidence of congenital and neonatal varicella during the prevaccination and postvaccination eras, found a 100% reduction in congenital varicella and 85% reduction in neonatal varicella since the vaccination was implemented in 2005  So, the apparent reduction in the numbers of congenital and neonatal varicella in the unvaccinated age groups appears a clear indication of vaccine herd effects.
  • Measles  Measles is a highly contagious disease (R0 estimated to be >10) that is preventable by immunization but requires a very high vaccine uptake to maintain herd immunity  The need for maintenance of this high coverage to stop transmission is illustrated by recent outbreaks in Europe and elsewhere following a misleading vaccine safety concern  there has been increased outbreaks of measles, in Europe, with more than 26 000 cases of measles reported, with 14 000 in France alone
  • Potential herd effects in HPV vaccination  The herd effect of HPV is not yet known  The direct effect was supported by a meta-analysis of 6 randomized controlled studies, showing a reduced frequency of high-grade cervical lesion by an OR of 0.14  with the high efficacy of the vaccine against cervical cancer, a vaccine herd effect might be expected, especially in high endemic regions  the effect of a vaccine herd effect in women by vaccinating men, or vice versa T. H. Kim et al.
  • Herd effect of interventions other than vaccination  lymphatic filariasis: , mass treatment with Ivermectin or diethyl carbamazine - the drug causes a reduction in transmission to susceptible even if they had not taken the drug  Pulmonary Tuberculosis: If increasing proportions of persons with pulmonary tuberculosis are diagnosed and treated early, the incidence of infection in the susceptible population should continue to decline
  • Theoretical Development: Recent concepts
  • Imperfect Immunity  vaccination does not confer solid immunity against infection to all recipients, (Example: multiple doses and monovalent vaccines in india)  the threshold level of vaccination required to protect a population increases  Vc=(1-1/R0)/E( Vc= critical vaccine coverage and E= vaccine effectiveness against infection transmission  if E is<(1 - 1/R0) it would be impossible to eliminate Fine et al
  • Heterogeneous Populations: Nonrandom Mixing  Heterogeneity in transmission arising from age related factor genetics , spatial and behavior factor.  critical threshold remains: Vc = (1 - 1/R0)/E (, R0 is a measure of the average number of secondary cases generated by a ‘‘typical’’ infectious person)  This average depends on how the various groups interact and can be calculated from a matrix describing how infection spreads within and between groups  Interactions are often observed to be more frequent within than between groups , resulting in a higher value of R0, and a larger vaccination threshold Fine et al
  • Nonrandom Vaccination  vaccination coverage differs between groups in a population, and these groups differ in their risk behavior, Thus, the simple results no longer follow.  Example: 2 groups. High risks: Ro=5, then Vc=80%, Low risk: Ro=1, then Vc=0%  Although nonrandom vaccination may offer theoretical opportunities for more cost-effective interventions, it raises problems in practice. Fine et al
  • Freeloaders  people who wish that everyone else around them is vaccinated except themselves  when coverage is close to Vc , or when vaccination is perceived to carry a risk similar to or greater than the infection, the incentive for a logical individual to receive a vaccine is lowered (declining measles and pertussis vaccine, after media scares about vaccines).  If immunity wanes over time, as in the case of pertussis or measles, there is a risk of focal outbreaks around the freeloaders
  • References  T. Jacob John & Reuben Samuel “Herd immunity and herd     effect: new insights and definitions” European Journal of Epidemiology 2000, 16: 601-606. Yash Paul “Herd immunity and herd protection” Vaccine 22 (2004) 301–302 Peter G Smith“Concepts of herd protection and immunity” Procedia in Vaccinology 2 (2010) 134–139 Harunor Rashid, Gulam Khandaker, and Robert Booy“Vaccination and herd immunity: what more do we know?” Curr Opin Infect Dis 2012, 25:243–249 Paul Fine, Ken Eames, and David L. Heymann‘‘Herd Immunity: A Rough Guide” Clinical Infectious Diseases 2011;52(7):911–916
  •  The oxford text book of public health 6th edition 2006  Park Text book of preventive and social medicine 21st edition 2011  Harrisson ‘s principle of internal medicine, 17th edition 2008  Tae hyong kim, Jennie johnstone, Mark loeb “Vaccine herd effect” Scandinavian Journal of Infectious Diseases, 2011; 43: 683–689  Michael Bröker ”Indirect effects by meningococcal vaccines:Herd protection vs. herd immunity” Human Vaccines 7:8, 881-882; August 2011.
  • Thank You