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Evidence on the infectious etiology of childhood leukemia: the role of low herd immunity (Greece).

OBJECTIVE: Acute lymphoblastic leukemia (ALL) among children may be a rare outcome of a delayed non-specific infection in situations of overall low herd immunity. We evaluated the hypothesis as to whether newly diagnosed ALL cases, compared to their controls, are characterized by lower herd immunity, as reflected in a more seronegative spectrum to several agents, with the exception of a strongly positive response to a single infectious agent, assumed to trigger ALL. METHODS: The study included 94 incident cases of ALL, from all pediatric hematology-oncology units of Greece, and 94, matched for age and gender, controls hospitalized with minor non-infectious conditions. The past exposure to common infections was assessed using 10 serological markers. RESULTS: There was little evidence for an association of ALL with the serology of any of the studied infectious agents among the very young children. In contrast, among children aged 5 years or older, leukemia was inversely associated with seropositivity to Epstein-Barr virus, human herpes virus-6, Mycoplasma pneumoniae and parvovirus B19. CONCLUSIONS: Among children aged 5 years or older the risk of leukemia may be higher when the low herd immunity for several agents is challenged by late infection from an agent that, as a rule, would attack children at a younger age.

Case-Control Studies↗

[Serologic assessment of measles herd immunity in the north-western region of Romania].

The most objective analysis of measles herd immunity could be made by sero-epidemiological study. In the population of North-West area of Romania we have evaluated the measles immune protection through a seroprevalence study, using an age stratified sample of population in witch the subjects from Cluj and Bistriţa-Năsăud counties were voluntarily involved. The measles antibody concentration was determined by immunoassay method using Hycor test. The database was performed in Microsoft Access and the statistics in Epi Info 2000. Levels higher then 40 arbitrary units (the cut-off of protection) of the measles antibody were met in 80% (IC95% : 75.09-84.01) of all subjects, 82.4% of the females and 84.9% of the urban area peoples. 98.3% of all subjects had detectable antibody levels. The protection increased by age: the adults had protective levels in at least 90% of cases. Global vaccine efficacy was 64.7% (IC95 % : 56.5 - 72.9), moderately decreasing with increasing age (the correlation coefficient--58.1%). In the assessed sample, the measles protection was the highest in adults, women and subjects from urban areas. The vaccine efficacy was relatively small, but the majority of subjects had detectable titers of measles antibody.

Adolescent↗

Herd immunity and measles.

The basic concept of herd immunity is directly applicable only under very special conditions. The agents of disease must be restricted to a single host species within which transmission occurs by relatively direct contact, and infection induces solid immunity. Also outbreaks must occur only in randomly mixing populations. In free-living populations, susceptibles are not distributed homogeneously but tend to cluster in subgroups defined by age and by such factors as ethnicity and socioeconomic status. The requisite for occurrence of epidemics, namely a large enough number of susceptibles in frequent contact with each other, exists in virtually all large populations, regardless of the total proportion of the population that is immune. Experience with measles illustrates these conditions. Total prevalence of immunity of greater than or equal to 90% in developing countries does not prevent annual epidemics among the susceptibles, most of whom are children younger than three years of age. Where vaccination is widely practiced, as in the United States since 1962, measles has continued to occur in poorly immunized subgroups that are characterized by low educational level and economic status, very young age, or religious beliefs forbidding acceptance of vaccine. Ultimate success of a systematic immunization program requires knowledge of distribution of susceptibles by age and subgroup and maximal effort to reduce the concentration of susceptibles throughout the community rather than aiming to reach any specific proportion of the overall population.

Child, Preschool↗

Herd immunity to filarial infection is a function of vector biting rate.

Despite the existence of an impressive body of work on human immune responses against filarial infections, the occurrence of a protective response to infection remains unclear. Here, we use a combined modelling and comparative data analysis framework to address this issue for human infections with the filarial parasite, Wuchereria bancrofti. By analogy with previous work, the analysis involves the comparison of observed field patterns of infection with epidemiological patterns predicted by a mathematical model of parasite immunity. Unlike most other human helminths, which are transmitted by ingestion or dermal penetration, exposure to infection with lymphatic filariasis can be measured explicitly in terms of vector mosquito biting rates, thereby also allowing, probably for the first time, examination of the suggested role of exposure in generating herd immunity to macroparasites. Observed field patterns in this study were derived from 19 different published studies, which gave parallel estimates of community exposure rates and the corresponding age--prevalence patterns of infection, while predictions of the epidemiological impact of herd immunity were obtained using a catalytic model framework. The results provide the first conclusive evidence to date that variations in the observed age--prevalence patterns of infection in filariasis can be effectively explained by the occurrence of an exposure-driven acquisition of herd immunity. We discuss this result in terms of implications for the new World Health Organization-led initiative for the global control of this parasitic disease.

Animals↗

Post mass-immunization measles outbreak in Taoyuan County, Taiwan: dynamics of transmission, vaccine effectiveness, and herd immunity.

OBJECTIVES: Analysis of national surveillance data and a seroepidemiologic investigation were conducted to elucidate the causes and epidemiologic characteristics of a measles outbreak in Taoyuan, Taiwan, 1994. METHODS: Measles cases were identified through a national surveillance system. Reported cases and their physician or school nurses were interviewed to trace additional suspect cases and were sampled for serologic diagnosis. Measles-specific IgG and IgM were assayed. A confirmed case was defined as being positive for measles IgM test but not having received measles vaccination within the previous 3 months. RESULTS: The outbreak began in Taoyuan City in December 1993 and continued to spread in primary schools and kindergartens, but caused only sporadic cases in neighboring towns. Among 42 confirmed cases, 15 (38%) were primary school children and 16 (38%) were kindergarten children. Among 24 confirmed cases with a vaccination record, 7 had one dose of vaccination, 4 had two doses of vaccination, and 13 (54%) were unvaccinated. The overall measles susceptible proportion at a kindergarten before the outbreak was 8.1% (17/209) and the overall measles cumulative incidence among susceptibles was 0.65 (11/17). CONCLUSIONS: A measles vaccination coverage of 82% with the first dose at 9 months of age and 63% with the second dose (measles, mumps, and rubella) at 15 months was inadequate to block measles virus circulation in Taoyuan City in 1994. The city center, with a growing population, represents a high risk as an epicenter for measles outbreaks. Measles outbreaks may occur in a school population with 92% herd immunity.

Antibodies, Viral↗

[The concept of herd immunity applied to the evaluation of vaccination programs].

The article concerns the definition and ways of estimation of indicators of herd immunity as applied to the analysis of the efficiency of vaccination programmes. Some important factors are discussed which determine the proportion of vaccinated individuals in the population necessary for decrease of incidence and eventually for elimination of the disease from a population. The problems related to definition and calculation of herd immunity in populations non uniform in terms of individual risk of infection are discussed.

Communicable Disease Control↗

Herd immunity to helminth infection and implications for parasite control.

Despite much research on immunological responses to helminth parasites, knowledge of the dynamic interplay between levels of herd immunity in humans and the rates of exposure, establishment and mortality of parasites remains limited. We describe here a simple mathematical model for the population dynamics of helminth infections which mirrors the development of a degree of acquired immunity within populations which are genetically heterogeneous with respect to immunological responsiveness. We interpret observed patterns in the age-specific intensity of infection and attempt to understand the possible effects of control measures based on chemotherapy and vaccination. Mass chemotherapy can, in some circumstances, reduce the level of herd immunity such that average worm burdens in the adult age classes rise above their precontrol levels. When certain individuals or groups are predisposed to heavy infection, selective or targeted drug treatment can have significantly greater impact than mass or random application. Conversely, model predictions suggest that effective parasite control by vaccination (if and when vaccines become available) is difficult to achieve in communities that are genetically heterogeneous in their ability to mount protective responses to infection.

Age Factors↗

Measles antibodies and herd immunity in 20- and 40-year-old Norwegians.

The introduction of a measles vaccination programme in Norway in 1969 using one dose of vaccine, and since 1983 two doses, was followed by a substantial decrease in the incidence of the disease. Since 1992, the annual incidence has been less than 20 cases. Small clusters and outbreaks have occasionally been observed among military personnel and unvaccinated children. This paper describes a seroepidemiological investigation of the level of immunity among 1,188 military conscripts, aged 18-28 years (mean 20.7) compared with 695 healthy 40-year-olds. The conscripts had been offered measles vaccine in infancy, in some cases also at 12-13 years of age, but they had also been exposed to wild measles virus, since the virus continued to circulate many years after the vaccination had started. The measles immunity in this group is considered to indicate the immunity level among the first 5 cohorts offered measles vaccine in Norway. The 40-year-olds had grown up in a community with no measles vaccination. Their level of immunity gives an indication of the level finally obtained when there are no vaccinations, and thus of the level that would induce herd immunity against measles in the Norwegian population. The aims of the vaccination programme must be to obtain a corresponding immunity. The results of the investigation show that the percentages with measles antibodies in the respective groups were 92.3 and 98.1. The observation of measles outbreaks among young Norwegian conscripts, as well as reports from several countries on outbreaks in university and college settings with levels of seropositivity of even more than 95%, indicate that the seropositivity in the 20-year-old group may be too low to afford protection, especially when this group is living under close conditions. Consideration should be given to the need for an intensification of the existing vaccination programme to ensure that the protection level needed for herd immunity is reached.

Adult↗

Pneumococcal pneumonia in the UK--how herd immunity affects the cost-effectiveness of 7-valent pneumococcal conjugate vaccine (PCV).

This study examines the potential clinical and economic benefits for adults arising from paediatric pneumococcal vaccination in the UK. A UK birth cohort model with a 10-year horizon and using a primary 4-dose paediatric 7-valent pneumococcal conjugate vaccine (PCV) schedule was populated with 1999 morbidity and mortality data scaled up to the UK population. Herd immunity effects on adult pneumococcal hospital-treated pneumonia, meningitis and septicaemia, but not on community-treated pneumonia, were calculated using the lower end of the confidence intervals published for the effects in the US. Universal paediatric pneumococcal immunisation would prevent 1168 deaths (1141 adults) and 7147 cases (1791 adults constituted by 32 meningitis, 37 septicaemia and 1722 pneumonia) of serious pneumococcal infection (meningitis, septicaemia, pneumonia) with a resultant direct (payor) cost per life year gained of 4360 pounds. The 7-valent PCV appears to be highly cost effective.

Adult↗

[Herd immunity and effectiveness of vaccination].

The effectiveness of vaccinations is discussed in relation to vaccine efficacy and effectiveness of vaccination programs. The types of epidemiological studies used in the assessment of vaccine effectiveness are presented, and most common sources of bias in such studies are listed. Basic formulas for calculation of vaccine effectiveness are given as applied for cohort and case-control studies. The definitions and ways of estimation of indicators of herd immunity as applied to the analysis of the effectiveness of vaccinations are presented.

Bacterial Infections↗

Relationship between neighbourhood-level killed oral cholera vaccine coverage and protective efficacy: evidence for herd immunity.

OBJECTIVES: The effectiveness of vaccines in populations must consider both direct and indirect protection. This study reanalyses data from a large individually randomized oral cholera vaccine trial that was conducted in rural Bangladesh from 1985 to 1990. A recent analysis of the results of that trial showed that the proportion of people in household clusters who received the vaccine was inversely related to placebo incidence during the first year of surveillance, which was attributed to herd immunity. METHODS: In this study we measure the relationship between neighbourhood-level oral cholera vaccine coverage and protective efficacy (PE) during a 2 year follow-up period, controlling for known effect modifiers. We link trial data to a household geographic information system to facilitate the neighbourhood-level analysis. Findings Neighbourhood-level PE can be partially explained by vaccine coverage after adjusting for ecological variables. CONCLUSIONS: The inverse relationship between vaccine coverage and efficacy illustrates that people living in high-coverage areas may be indirectly protected from cholera because people living around them are vaccinated.

Adult↗

'Clustering of exemptions' as a collective action threat to herd immunity.

In this paper, we examine the phenomenon of 'clustering of exemptions' to childhood vaccination, and the dangers this poses both to those exempted as well as the general population. We examine how clusters of exemptions might form through collective action as described by Thomas Schelling, and how religious groups who live in close proximity to one another can "self-select" in a way that exacerbates this phenomenon. Given the growing number of exemptions and the increasing visibility of the anti-vaccine movement, policy makers must be vigilant for dangerous clustering in order to avoid loss of herd immunity.

Child↗

Imperfect vaccines and herd immunity to HIV.

A number of prophylactic vaccines against human immunodeficiency virus (HIV) have passed through phase I clinical trials, and phase II clinical trials are now being planned. These vaccines are not expected to be perfect and might fail in a number of different ways. This paper shows how to equate different aspects of imperfection in a prophylactic vaccine in terms of impact upon levels of herd immunity, and hence upon the vaccine coverage required for eradication. Such comparisons reveal that an otherwise perfect vaccine that gives protection which wanes with a half-life of 10 years is only as good as a vaccine that works in 30% of people giving them complete, lifelong protection. The paper goes on to compare predicted patterns of seroconversion that would be observed in clinical trials and in community-wide vaccination campaigns for vaccines that confer the same levels of herd immunity but are imperfect in different ways.

AIDS Vaccines↗

Epidemiology of pertussis in Denmark: the impact of herd immunity.

BACKGROUND: An evaluation is presented of the Danish pertussis immunization programme, which consists of three injections of plain whole-cell pertussis vaccine given alone at ages 5 weeks, 9 weeks, and 10 months. DATA: The incidence of pertussis in vaccinated and unvaccinated children since the start of vaccination was obtained from the notification system for infectious diseases. Data for vaccination coverage were obtained from the National Social Security. The data for 1980-1986 were supplemented with data from culture-verified cases and hospitalized cases. RESULTS: Compared with other countries using four injections, incidence rates in Denmark are high, especially in pre-school years, leaving infants at a relatively high risk for contracting pertussis from siblings. However, compared with the era before general vaccination, the incidence of pertussis has fallen to one-sixteenth of its former levels. Today, only one in 20 vaccinated, and one in six unvaccinated children develop pertussis before the age of 15 years. This considerable fall, which has also occurred among unvaccinated children, is used to elucidate the importance of herd immunity, which, with the relatively high vaccination coverage in Denmark, was found to play a major role. CONCLUSIONS: The importance of herd immunity is stressed, and it is recommended that a fourth injection of pertussis vaccine is introduced to bring incidence rates down to the very low values found in countries with more intensive vaccination programmes.

Adolescent↗

The concept of herd immunity and the design of community-based immunization programmes.

The paper focuses on the concepts of transmission success and herd immunity and their relevance to the design of community-based immunization programmes for the control of infectious diseases. Recent work in a number of areas is reviewed, including the influence of mass vaccination on the average age of infection and the incidence of morbidity due to infection and vaccination, the age window of susceptibility and the problems of vaccine programme design in developing countries, the interaction between vaccine efficacy and vaccine safety and the design of vaccination programmes for the control of sexually transmitted infections. Discussions centre on the interplay between an understanding of the transmission dynamics of an infection and the design of community-based control programmes.

Adolescent↗

On the solution of mathematical models of herd immunity in human helminth infections.

The general solution of the mathematical model of herd immunity to human helminth infections recently proposed by Anderson and May is obtained. The numerical solution of a more accurate biological model is indistinguishable from the corresponding exact solution of a more tractable mathematical model. Computer simulations of some particular cases of this model support the notion that both ecological and immunological factors determine the observed convex patterns of age-prevalence and age-intensity curves of human helminth infections.

Animals↗

Vaccination and herd immunity to infectious diseases.

An understanding of the relationship between the transmission dynamics of infectious agents and herd immunity provides a template for the design of effective control programmes based on mass immunization. Mathematical models of the spread and persistence of infection provide important insights into the problem of how best to protect the community against disease.

Age Factors↗

Influence of the vaccination regime on the herd immune response for swine fever.

Surveys in three areas with emergency vaccination programmes revealed that 86-94% of the pigs vaccinated in the initial mass campaign had developed an adequate antibody titre against swine fever as compared with 29-55% of the pigs involved in supplementary vaccination campaigns. The serological response of piglets born from immunised sows rose with the age of vaccination from 11% at 5-6 weeks to 42% at 7-8 weeks and 77% at 9-10 weeks. In piglets born from immunised sows, a 50% 'take' of the vaccine was not obtained before the age of 8-9 weeks. Re-vaccination of gilts born from immunised dams improved the immune status to almost the level observed after mass campaigns. To strengthen herd immunity in vaccination areas, the age of supplementary vaccination has been raised to 7-9 weeks, while breeding gilts are re-vaccinated when 6-7 months old.

Age Factors↗