Surveillance of pertussis in the CSSR. IV. Immunological surveys of antibodies to pertussis and parapertussis in the Bohemian regions and in Slovakia in 1958 - 1971.

A comparison of the results of repeated immunological surveys with the notification of morbidity and mortality to pertussis and parapertussis revealed direct dependence and simultaneously confirmed the effectiveness of Czechoslovak vaccine. Immunological surveys should be continued in spite of the fact that morbidity of pertussis is low at present, because immunological surveys may lead to timely detection of shortcomings in the quality of vaccination and vaccine. The results after 14 years of systematic vaccination and revaccination and consequent follow-up to the state of immunity in the population and of other factors in the pertussis surveillance programme rank among the other achievements of epidemiology and hygiene in Czechoslovak health services. Contemporary immunological surveys show that the state of immunity in Czechoslovak child population is such as to exclude the occurrence of pertussis in epidemics in the nearest future. The situation is different in parapertussis where epidemic incidence is still possible and where epidemics regularly occur in children of prae-school age.     

Pathogen adaptation under imperfect vaccination: implications for pertussis

Mass vaccination campaigns have drastically reduced the burden of infectious diseases. Unfortunately, in recent years several infectious diseases have re-emerged. Pertussis poses a well-known example. Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination. A distinction is made between infection in immunologically naive individuals (primary infection) and infection in individuals whose immune system has been primed by vaccination or infection (secondary infection). The results show that (i) vaccination with an imperfect vaccine may not succeed in reducing the infection pressure if the transmissibility of secondary infections is higher than that of primary infections; (ii) pathogen strains that are able to evade the immunity induced by vaccination can only spread if escape mutants incur no or only a modest fitness cost and (iii) the direction of evolution depends crucially on the distribution of the different types of susceptibles in the population. We discuss the implications of these results for the design and use of vaccines that provide temporary immunity.     

Impact of vaccination and birth rate on the epidemiology of pertussis: a comparative study in 64 countries

Bordetella pertussis infection remains an important public health problem worldwide despite decades of routine vaccination. A key indicator of the impact of vaccination programmes is the inter-epidemic period, which is expected to increase with vaccine uptake if there is significant herd immunity. Based on empirical data from 64 countries across the five continents over the past 30–70 years, we document the observed relationship between the average inter-epidemic period, birth rate and vaccine coverage. We then use a mathematical model to explore the range of scenarios for duration of immunity and transmission resulting from repeat infections that are consistent with empirical evidence. Estimates of pertussis periodicity ranged between 2 and 4.6 years, with a strong association with susceptible recruitment rate, defined as birth rate × (1 − vaccine coverage). Periodicity increased by 1.27 years on average after the introduction of national vaccination programmes (95% CI: 1.13, 1.41 years), indicative of increased herd immunity. Mathematical models suggest that the observed patterns of pertussis periodicity are equally consistent with loss of immunity that is not as rapid as currently thought, or with negligible transmission generated by repeat infections. We conclude that both vaccine coverage and birth rate drive pertussis periodicity globally and that vaccination induces strong herd immunity effects. A better understanding of the role of repeat infections in pertussis transmission is critical to refine existing control strategies.     

Pertussis in England and Wales: an investigation of transmission dynamics and control by mass vaccination

The epidemiology of pertussis and its prospects for control by mass vaccination in England and Wales are investigated by analyses of longitudinal records on incidence and vaccine uptake, and horizontal data on age-stratified case reports. Mathematical models of the transmission dynamics of the infection that incorporate loss of natural and vaccine-induced immunity plus variable vaccine efficacy are developed, and their predictions compared with observed trends. Analyses of case reports reveal that the individual force of infection is age dependent, with peak transmission in the 5- to 10-year-old age class. A model incorporating this age dependency, along with partial vaccine efficacy and loss of vaccine-induced immunity, generates predicted patterns that best mirror observed trends since mass vaccination was inaugurated in 1957 in England and Wales. Model projections accurately mirror the failure of mass vaccination to increase the inter-epidemic period of the infection (three years) over that pertaining before control. The analysis suggests that this is due to the impact of partial vaccine efficacy. Projected trends do not accurately reflect the low levels of pertussis incidence reported between epidemics in the periods of high vaccine uptake. This is thought to arise from a combination of factors, including loss of natural and vaccine induced immunity, biases in case reporting (where reporting efficiency is positively associated with the incidence of pertussis), and seasonal variations in transmission. Model predictions suggest that the vaccination of 88% of each birth cohort before the age of 1 year will eliminate bacterial transmission, provided the vaccine confers lifelong protection against infection. If vaccine-induced immunity is significantly less than lifelong (or if vaccination fails to protect all its recipients) repeated cohort immunization is predicted to be necessary to eliminate transmission. Future research needs are discussed, and emphasis is placed on the need for more refined data on vaccine efficacy, the duration of natural and vaccine-induced immunity and the incidence of clinical pertussis and subclinical infections (perhaps by the development of reliable serological tests). Future mathematical models will need especially to incorporate seasonality in transmission.     

Impact of vaccination on the infectious diseases epidemiology: example of pertussis

Several vaccines are now routinely used since fifty years in different developed countries. Their principal impact has been to decrease morbidity and mortality of the infectious diseases they are targeting. One disease, smallpox, is eradicated, poliomyelitis will be soon, diphteria is controlled in several countries but pertussis is still endemic although an efficacious vaccine was used. Why? Pertussis is an example of an infection for which the immunity of the population has changed after the introduction of generalized vaccination with killed whole cell pertussis vaccines, from a natural immunity due to infection to different types of vaccine-induced immunity. These different types of immunity have changed the protection against infection, disease and transmission. The impact of the generalized vaccination in a human population has been an important change in the epidemiology of the disease. In fact, a child-to-child transmission observed before the introduction of vaccination is now replaced by an adolescent-adult to infant transmission. The major consequence is an increase in the mortality and morbidity in non vaccinated infants mostly contaminated by their parents. Researches undertaken on the agent of the disease, the bacterium, Bordetella pertussis, conducted to the development of subunits vaccines, efficacious and better tolerated by infants than whole-cell vaccines. Many developed countries decided to change vaccines but also to add vaccine boosters for adolescents and adults in order to stop the transmission of the disease to infants. However, even after 15 years of studies in many countries, pertussis is still underestimated in adults and generalized adult vaccination remains difficult. The new goal now is to give information to medical students and health care workers in general in order to increase adolescent and adult's vaccination coverage.     

Seroprevalence of pertussis in The Netherlands: evidence for increased circulation of Bordetella pertussis

Background

In many countries, the reported pertussis has increased despite high vaccination coverage. However, accurate determination of the burden of disease is hampered by reporting artifacts. The infection frequency is more reliably estimated on the basis of the prevalence of high IgG concentrations against pertussis toxin (IgG-Ptx). We determined whether the increase in reported pertussis in the last decade is associated with an increase in the number of infections.

Methodology/Principal Findings

In a cross-sectional population-based serosurveillance study conducted in 2006-07, from a randomly selected age-stratified sample of 7,903 persons, serum IgG-Ptx concentrations were analyzed using a fluorescent bead-based multiplex immuno assay. In 2006-07, 9.3% (95%CI 8.5-10.1) of the population above 9 years of age had an IgG-Ptx concentration above 62.5 EU/ml (suggestive for pertussis infection in the past year), which was more than double compared to 1995-96 (4.0%; 95%CI 3.3-4.7). The reported incidence showed a similar increase as the seroprevalence between both periods.

Conclusions

Although changes in the vaccination program have reduced pertussis morbidity in childhood, they have not affected the increased infection rate in adolescent and adult pertussis. Indeed, the high circulation of B. pertussis in the latter age-categories may limit the effectiveness of pediatric vaccination.     

Vaccine coverage: recent trends and future prospects.

OBJECTIVE--To assess the feasibility of achieving the target of 95% coverage for the childhood immunisation schedule by 1995 and to determine the influence of sociodemographic factors and information systems on recent trends. DESIGN--Analyses of trends in quarterly vaccination data for diphtheria, pertussis, and measles in health districts between February 1988 and February 1991. SETTING--District health authorities in England and Wales, and health and social services boards in Northern Ireland. SUBJECTS--Cohorts of children whose youngest member had reached the target age of 18 months for receiving the third doses of diphtheria and pertussis vaccines and 2 years for receiving measles vaccine. RESULTS--Predicted coverage levels for mid-1995 were in excess of 95% for diphtheria, pertussis, and measles vaccines. In the 118 districts that continuously reported between February 1988 and February 1991 the increase in coverage was 6% for diphtheria and 13% for pertussis and measles vaccines. 1991 coverage depended primarily on 1988 coverage. The additional effects of deprivation, change in computer system, and child population size achieved at most only marginal statistical significance. CONCLUSIONS--The government''s target of 95% coverage by 1995 is realistic, although projections should be viewed with caution. Several national vaccination initiatives are likely to have contributed to the recent steady increase in coverage. Updating and validation exercises are likely to improve recorded coverage.     

Molecular epidemiology of Bordetella pertussis in Taiwan, 1993-2004: suggests one possible explanation for the outbreak of pertussis in 1997

Pertussis reemerges periodically despite high pertussis vaccination coverage in many countries. We used prn and fim3 gene sequences and pulsed-field gel electrophoresis (PFGE) to analyze the molecular epidemiology of 168 clinical isolates of Bordetella pertussis during 1993-2004, and deduced possible reasons for an outbreak in 1997 in Taiwan. In Taiwan, during 1996-1997, a shift of prn1 to prn2 was reflected in a transition of PFGE group I to group IIIa; during 2000-2001, the change from fim3A to fim3B was displayed in transition of PFGE group IIIa to group IIIb. These changes were also consistent with the two peaks of pertussis incidence in 1997 and 2000. In 1997, a larger than expected increase in the incidence of pertussis occurred and isolates were characterized by complicated pulsotypes, appearance of many new profiles and an unusual presence of prn3. Based on a high resemblance of PFGE profiles and the same virulence genes, a similar shift of circulating strains was observed in European countries as well as Taiwan; thus, the high incidence of pertussis in 1997 may be due to an international expansion of B. pertussis strains from a similar source. This study provides further elucidation of the global molecular epidemiology of B. pertussis.     

Effectiveness of pertussis vaccination and duration of immunity

Background:A resurgence of pertussis cases among both vaccinated and unvaccinated people raises questions about vaccine effectiveness over time. Our objective was to study the effectiveness of the pertussis vaccine and characterize the effect of waning immunity and whole-cell vaccine priming.Methods:We used the test-negative design, a nested case–control study with test-negative individuals as controls. We constructed multivariable logistic regression models to estimate odds ratios (ORs). Vaccine effectiveness was calculated as (1 – OR) × 100. We assessed waning immunity by calculating the odds of developing pertussis per year since last vaccination and evaluated the relative effectiveness of priming with acellular versus whole-cell vaccine.Results:Between Dec. 7, 2009, and Mar. 31, 2013, data on 5867 individuals (486 test-positive cases and 5381 test-negative controls) were available for analysis. Adjusted vaccine effectiveness was 80% (95% confidence interval [CI] 71% to 86%) at 15–364 days, 84% (95% CI 77% to 89%) at 1–3 years, 62% (95% CI 42% to 75%) at 4–7 years and 41% (95% CI 0% to 66%) at 8 or more years since last vaccination. We observed waning immunity with the acellular vaccine, with an adjusted OR for pertussis infection of 1.27 (95% CI 1.20 to 1.34) per year since last vaccination. Acellular, versus whole-cell, vaccine priming was associated with an increased odds of pertussis (adjusted OR 2.15, 95% CI 1.30 to 3.57).Interpretation:We observed high early effectiveness of the pertussis vaccine that rapidly declined as time since last vaccination surpassed 4 years, particularly with acellular vaccine priming. Considering whole-cell vaccine priming and/or boosters in pregnancy to optimize pertussis control may be prudent.Whooping cough, or pertussis, is a highly contagious respiratory infection that has been inadequately controlled compared with other vaccine-preventable diseases. The incidence of pertussis in Canada decreased from 156 cases per 100 000 population during the prevaccination era to a historic low of 2.0 per 100 000 in 2011, increased to 13.9 in 2012, and then decreased to 3.6 in 2013.¹Ontario, Canada’s most populous province with a population of 13.5 million in 2013, experienced a localized outbreak in 2012. This outbreak started in a largely unvaccinated religious community and disproportionately affected infants, but then spread to the general population and mostly involved adolescents.² Consequently, the outbreak raised questions about product-specific vaccine effectiveness and waning immunity.Pertussis vaccines have been available in Ontario for more than 70 years. In 1997, owing to concerns about safety and effectiveness, acellular pertussis vaccine replaced the whole-cell product that had been in use since 1984.^3–5 In Ontario, only the 5-component acellular vaccine (containing pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3) has been available for infants and toddlers. Vaccination against pertussis is recommended at 2, 4, 6 and 18 months, and at 4–6 years. In 2003, an adolescent dose at 14–16 years was introduced, and in 2011, a program was started for single-dose adult vaccination against pertussis.⁶Other jurisdictions in Canada, the United States and Australia have reported lower effectiveness with the acellular product and rapidly waning immunity.^7–11 Canada has a unique history of using a whole-cell vaccine with lower effectiveness, and also has different secular trends in pertussis incidence and vaccination coverage, necessitating local evaluation of the effectiveness of the pertussis vaccine to inform vaccination policy. Our objective was to study the effectiveness of the pertussis vaccine in Ontario while characterizing the effect of waning immunity and whole-cell vaccine priming.     

The epidemic situation in relation to HIV infection in Ukraine (1987-1997)

The analysis of the dynamics of the epidemic process for 10 years made it possible to find out the presence of two separate epidemic waves of HIV infection. The first wave (1987-1994) was manifested as the slow type of the development of the epidemic, characterized mainly by sexual transmission. During this period 398 persons with HIV infection were detected, 24 persons were found to have AIDS; of these, 13 persons died. The second epidemic wave began in 1995 and was due to the spread of HIV among users of drugs introduced by injection. By the end of 1995 the number of HIV carriers was 34 times greater than that of 1994, reaching 1490 persons. In 1996-1997 this figure increased 8 times (annually). The number of AIDS patients rose to 420 persons. The most unfavorable regions with respect to HIV infection and AIDS morbidity were determined. The western regions of the Ukraine were noted to be in a more favorable situation in this respect with infection indices being lower more than 30 times. Up to 80% of all infected persons were found to be addicts introducing drugs intravenously. Growing morbidity in sexually transmitted disease, particularly in syphilis, contributed to the deterioration of the epidemiological situation. The conclusion was made on the necessity of introducing new prophylactic programs and expanding current ones. The signs of stabilization in Odessa and Nikolayev were observed; in these cities pilot programs aimed at the strategy of the "decrease of harm" have been introduced (in collaboration with UNAIDS) since 1996.     

Multiple-locus variable-number tandem repeat analysis of Dutch Bordetella pertussis strains reveals rapid genetic changes with clonal expansion during the late 1990s

Bordetella pertussis, the causative agent of whooping cough, has remained endemic in The Netherlands despite extensive nationwide vaccination since 1953. In the 1990s, several epidemic periods have resulted in many cases of pertussis. We have proposed that strain variation has played a major role in the upsurges of this disease in The Netherlands. Therefore, molecular characterization of strains is important in identifying the causes of pertussis epidemiology. For this reason, we have developed a multiple-locus variable-number tandem repeat analysis (MLVA) typing system for B. pertussis. By combining the MLVA profile with the allelic profile based on multiple-antigen sequence typing, we were able to further differentiate strains. The relationships between the various genotypes were visualized by constructing a minimum spanning tree. MLVA of Dutch strains of B. pertussis revealed that the genotypes of the strains isolated in the prevaccination period were diverse and clearly distinct from the strains isolated in the 1990s. Furthermore, there was a decrease in diversity in the strains from the late 1990s, with a remarkable clonal expansion that coincided with the epidemic periods. Using this genotyping, we have been able to show that B. pertussis is much more dynamic than expected.     

HIV infection in children perinatally infected

During the period from 1987 to the middle of 1996 only 20 children were born of HIV-infected women, while during the following 1.5 years the number of such children were 59, the maximum number of seropositive children being registered in Kaliningrad and the Kaliningrad region, in the Krasnodar Territory, Stavropol and Nizhny Novgorod (altogether 46 children). Out of 79 children born of HIV-infected mothers during the whole period of the epidemic, 8 children died. Out of the children born before 1995 who remained alive, 9 children were struck off the register after 3 years of observation due to the absence of HIV infection. By the end of 1997 63 children were registered, the majority of them born in 1996-1997.     

Genomic analysis and comparison of Bordetella pertussis isolates circulating in low and high vaccine coverage areas

The aim of this study was to analyze Bordetella pertussis isolates circulating, between 1991 and 1995, in Niakhar, Senegal area where the pertussis vaccination coverage was low and to compare them with those circulating in France, before and after introduction of generalized pertussis vaccination for toddlers in 1959. We carried out bacteriological analyses, typing, genotyping and DNA microarray analyses. We found that the isolates circulating in Senegal between 1991 and 1995 are part of the same Pulsed Field Gel Electrophoresis Group, express the same antigens and possess the same gene deletions than isolates circulating in France before the introduction of vaccination, but are different from those circulating in 1991-1995. We confirmed the influence of pertussis vaccination on circulating isolates and that isolates vary with the pertussis cycle.     

The molecular epidemiological aspects of hiv-infection spreading in Perm region

Retrospective analysis of HIV-infection spreading in Perm region in conjunction with the genetic characterization of viral subtypes circulated on this territory from 1988 (when 1st case of infection was detected) until 2005 was performed. Analysis of epidemic process allowed to determine three periods of its development basing on both epidemic intensity and nature of circulating HIV-1 subtypes. During 1988 - 1996 (first period), when viral population was heterogenous (simultaneous circulation of three HIV-1 subtypes) with multiple routes of transmission, the epidemic process was characterized by low intensity. High incidence of HIV-infection among injection drug users and high homogeneity of circulated HIV-1 variants (98% of isolated variants belonged to HIV-1 subtype A with low level of genetic variability) were characteristics of the second period lasted from 1997 to 2001. Decrease in HIV-infection incidence in 2002-2005 was accompanied by the increase of HIV-1 transmission through heterosexual contacts and continuation of subtype A predominance between isolates. However increase in heterogeneity of viral population during this period, which manifested as increase of env and pol genes polymorphism, was detected.     

HIV infection in the penitentiaries of Ukraine

In connection with a sharp increase of the number of HIV-infected persons in the Ukraine the natural growth of the number of such persons in penitentiary institutions was registered, starting from 1995 (455 persons in 1995, 2,937 persons in 1996, 2,779 persons in 1997 and 173 persons during 5 months of 1998). 83% of HIV infection persons were drug addicts introducing drugs intravenously. In 1997 the strategy of decreasing the risk of infection in penitentiary institutions was worked out in collaboration with UNAIDS experts: repressive and isolation measures were replaced with measures aimed at the "decrease of harm". Special attention is given to circumstances aggravating the epidemic situation in HIV infection, and particularly at the sharp growth of morbidity in tuberculosis and syphilis (10.6 and 10.3 times respectively in 1997 in comparison with 1993). In addition, in 1997 the number of person having drug addiction was noted to increase 2.3 times in comparison with 1993. The necessity of taking constant information and educational measures aimed at decreasing the risk of the spread of HIV infection is emphasized.     

Restriction analysis of Bordetella pertussis DNA isolated from patients with whooping cough in 1968 and 1995-98 and B. pertussis used for production of national vaccine strains

The genotypic and serotypic analysis of B. pertussis strains isolated from the nasopharynx of children with whooping cough in the years 1968 and 1995-98 and B. pertussis vaccine strains was the aim of this study. The genotyping of the examined strains was done by electrophoretic division of DNA in pulsed field. The 3 types (A, B, C) and 2 subtypes (A1 and A2) of DNA restriction patterns were determined for the B. pertussis strains isolated in 1968. The 2 types (D and E) and 10 subtypes (D1-D10) of DNA restriction patterns were identified for B. pertussis strains from the years 1995-98. The DNA restriction patterns of B. pertussis strains isolated in the years 1968 and 1995-98 were not identical what was the evidence of the fact that in the sixties and nineties whooping cough was caused by different B. pertussis clones. The different DNA profiles were also observed for vaccine strains as well as for vaccine strains and current isolates. Differences in DNA patterns of vaccine strains and B. pertussis strains isolated in the years 1995-98 indicated a relationship possibility in some cases while lack of relationship between these strains in other cases. Serotyping of the examined B. pertussis strains was performed by the agglutination method with the sera against B. pertussis agglutinogens 1, 2 and 3. Most strains--15 (75%) isolated in 1968 possessed only agglutinogens 1 and 3. Serotype 1, 2, 3 was most frequently observed among isolates from the years 1995-98. This study indicates the expediency of periodical change of B. pertussis vaccine strains in the aspect of whooping cough resurgence in the years 1994-95 and 1997-98.     

Quantification of the effect of control strategies on classical swine fever epidemics

Emergency vaccination during an epidemic of classical swine fever virus (CSFV) has become a serious option because of the ethical problems of strategies with massive culling and the availability of a marker vaccine that reduces virus transmission. Here we present a model of between-herd CSFV transmission, which quantifies the effect of control strategies with and without vaccination. We estimate the model parameters from data of the Dutch CSFV epidemic of 1997/1998. With the model, a set of control strategies is compared, consisting of five control measures in several combinations. Consequently, the following general requirements of successful strategies can be formulated. First, to achieve extinction of a CSFV epidemic, transmission through transport should be prevented and the indirect virus transmission, i.e. all transmission not through animal contacts, should at least be halved, either by vaccination or by culling of the susceptible pig population. Second, to minimize the size and duration of an epidemic, the extinction requirements should be met quickly and indirect virus transmission should be reduced by far more than a half. Although the origin of the model parameters let the requirements in fact be only applicable for the south-eastern part of the Netherlands, it is argued that epidemics in other areas will not need stricter control strategies.     

Seasonality and comparative dynamics of six childhood infections in pre-vaccination Copenhagen

Seasonal variation in infection transmission is a key determinant of epidemic dynamics of acute infections. For measles, the best-understood strongly immunizing directly transmitted childhood infection, the perception is that term-time forcing is the main driver of seasonality in developed countries. The degree to which this holds true across other acute immunizing childhood infections is not clear. Here, we identify seasonal transmission patterns using a unique long-term dataset with weekly incidence of six infections including measles. Data on age–incidence allow us to quantify the mean age of infection. Results indicate correspondence between dips in transmission and school holidays for some infections, but there are puzzling discrepancies, despite close correspondence between average age of infection and age of schooling. Theoretical predictions of the relationship between amplitude of seasonality and basic reproductive rate of infections that should result from term-time forcing are also not upheld. We conclude that where yearly trajectories of susceptible numbers are perturbed, e.g. via waning of immunity, seasonality is unlikely to be entirely driven by term-time forcing. For the three bacterial infections, pertussis, scarlet fever and diphtheria, there is additionally a strong increase in transmission during the late summer before the end of school vacations.     

Specific features of the typhoid fever epidemic process in organized collective

During the chronic water epidemic of typhoid fever in Tajikistan in 1996-1997 specific features of the epidemic process dynamics in groups of servicemen were studied in several cities. The infective agent was proved to be transmitted by the alimentary route and through everyday contacts, the water route of transmission playing the most important role. The early clinical and epidemiological signs of the water outbreak of typhoid fever and the risk factors were established. The clinical and epidemiological aspects of vaccination were analyzed.     

Children, adolescents and HIV infection

The analysis of the occurrence of HIV infection in adults, children and adolescents under 18 years of age on the basis of statistical data by February 1, 1997, is presented. The total number HIV-infected persons registered by this date was 6,232; among them 902 (14.5%) were children and adolescents. 267 children were infected in the hospital focus of HIV infection; of these, 80 children (30%) died of AIDS during the period of 1989-1997. In 1992 only 16 adolescents, HIV infected were registered, while in 1995 the number of HIV-infected adolescents was 34, in 1996 their number rose to 144 and in 1997, to 435. The main cause of adolescent infections (80%) was the intravenous injection of narcotic drugs.