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Pertussis outbreak in primary and secondary schools in Ludwigslust, Germany demonstrating the role of waning immunity
Abstract
A pertussis outbreak primarily affecting school-age children in Ludwigslust, Germany, was investigated in 2006 to estimate attack rates and relative risk of pertussis according to time since last vaccination, after a complete primary course. Results suggested waning immunity beginning approximately 5 years after the last dose of pertussis vaccination. Most cases could have been prevented by earlier booster vaccination.
... Laboratory diagnosis, initiated at the discretion of the physician, consists of cultural isolation or detection of B. pertussis by PCR in nasopharyngeal swabs or secretions or serological diagnosis by means of an elevated pertussis-specific IgA-antibody concentration in a single serum sample or a 4-fold increase in IgG-or IgA-pertussis-specific antibodies using any commercially available test kit (e.g. Serion ELISA classic measuring IgG-[PT, FHA (filamentous hemagglutinin)] and IgA-(PT, FHA) antibodies, Genzyme Virotech GmbH ELISA measuring IgG-and IgA-antibodies against PT, or Bordetella pertussis IgG Virastripe ® , an immunoassay also measuring IgG-antibodies against PT and FHA (produced by Viramed) [19]. The majority of the 18,080 cases notified to RKI between January 2002 and December 2007 were laboratory confirmed (93.8%); 1.9% fulfilled the clinical case definition and were epidemiologically linked to a laboratory confirmed case and 4.4% solely fulfilled the clinical case definition. ...
... From 2002 to 2007, 16.0% of notified pertussis cases in FEG were reported as epidemiologically linked; 9.4% occurred in clusters of 5 or more cases. The largest cluster that occurred in MV in 2005-2006 consisted of 80 notified cases, but active case-finding during an outbreak investigation identified a further 24 persons who fulfilled the clinical case definition [19] ...
... The increase in incidence since 2004 was most marked in children between 5 and 14 years of age, a high proportion of whom had received 4 doses of pertussis vaccine in infancy, suggesting that waning immunity was playing a role. This is supported by an outbreak investigation per formed in a highly vaccinated school population in Mecklenburg Western-Pomerania in 2006, which showed a markedly higher attack rate in children who had received their fourth vaccine dose >5 years previously [19]. Increased vaccination coverage may lead to a period of decreased natural boosting, which may "unmask" the effect of waning vaccine-induced immunity, causing incidence to increase despite a lower level of transmission. ...
Abstract Background Current and past pertussis epidemiology in the two parts of Germany is compared in the context of different histories of vaccination recommendations and coverage to better understand patterns of disease transmission. Methods Available regional pertussis surveillance and vaccination coverage data, supplemented by a literature search for published surveys as well as official national hospital and mortality statistics, were analyzed in the context of respective vaccination recommendations from 1964 onwards. Results Routine childhood pertussis vaccination was recommended in the German Democratic Republic (GDR) from 1964 and in former West German states (FWG) from 1969, but withdrawn from 1974–1991 in FWG. Pertussis incidence declined to
... An overview of epidemiology studies in Western European countries is shown in Table 2. Countries for which study data were available included Austria [35], Belgium [36][37][38], France [39][40][41][42][43][44][45][46], Germany [47][48][49][50][51][52], Ireland [53,54], Luxembourg [55], The Netherlands [56][57][58][59][60][61][62][63], Switzerland [64] and the UK [65][66][67][68][69][70][71][72][73]. ...
... among adults aged C 20 years. The overall attack rate was 15.0% (70/467) [50]. In a study of infected households in Germany between 1992 and 1994, 104 children (85%) and 18 adults (15%) were the source of pertussis. ...
Pertussis (whooping cough) epidemics persist globally despite high vaccine coverage among infants and young children. The resurgence of pertussis in high-income countries is partly due to waning vaccine immunity, resulting in a pool of unprotected adolescents and adults. However, pertussis is generally less severe in adolescents and adults, and this difference in presentation means it can often be unrecognised by healthcare professionals, meaning that it is largely under-diagnosed in older populations. A systematic search of MEDLINE, EMBASE and BIOSIS was undertaken to identify studies published between 1 January 1990 and 17 June 2019, with information on pertussis epidemiology and mortality in school-aged children, adolescents and adults in Europe. A formal statistical comparison (e.g. using meta-analyses) was not possible because of the mix of methodologies reported. There were 69 epidemiological studies and 19 mortality studies identified for review. Over the past decade, the reported incidence of notified pertussis cases varied widely between European countries, which is likely associated with differences in surveillance systems, diagnostic techniques and reporting regulations. However, several studies show that pertussis is circulating among adolescents and adults in Europe, and although pertussis-related morbidity and mortality are highest in infants, there is evidence that adults aged > 50 years are at increased risk. For example, in a hospital-based surveillance study in Portugal, between 2000 and 2015, 94% of hospitalised pertussis cases were infants aged < 1 year, with a case fatality rate (CFR) of 0.8%; however, among hospitalised adult cases of pertussis, the CFRs were 11.5% (aged 18–64 years) and 17.4% (aged > 65 years). Very few European countries currently include pertussis boosters for adults in the national immunisation strategy. In addition to increasing pertussis vaccination coverage in adolescents and adults, mitigation strategies in European countries should include improved diagnosis and treatment in these populations.
... In addition, the risk of developing pertussis was significantly higher among children aged !8 years and those in which !6 years had passed since the fourth dose of vaccine. Previous studies in other countries also demonstrated that older children and those in which a longer period of time had passed since the last dose of vaccine had a higher risk of developing pertussis [18][19][20][21], although the preventive effect of DTaP vaccine was highly persistent for approximately 5 years [4][5][6][7][8][9]. Therefore, the present results are consistent with these studies. ...
... Therefore, the present results are consistent with these studies. Considering both our data and those of other studies [4][5][6][7][8][9][18][19][20][21], it is not surprising that there has been a resurgence of pertussis in elementary schoolaged children [1]. ...
Objective
The Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6–12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program.
Methods
Subjects included children aged ≥3 months who visited a collaborating hospital due to pertussis-specific cough between October 2017 and November 2019. All subjects underwent diagnostic tests for pertussis, and those diagnosed as positive were regarded as cases. Subjects diagnosed as pertussis-negative were classified as controls. Vaccination history was collected using a questionnaire administered to parents with reference to immunization records. Logistic regression models were employed to calculate the odds ratio (OR) and 95% confidence interval for laboratory-confirmed pertussis.
Results
Of 187 recruited subjects (120 cases and 67 controls), questionnaire responses were obtained for 145 subjects (95 cases and 50 controls). Compared with unvaccinated subjects, the vaccine effectiveness (VE) of 4 doses was 70% among all subjects and reached to 90% with marginal significance among subjects under 6 years of age. However, among school-aged subjects, the VE was not suggestive of protection against pertussis (VE: 8%). For vaccinees given 4 doses, the OR for developing pertussis increased significantly with longer duration since the fourth dose (compared with <4.5 years, OR of 6.0–8.2 years = 5.74; OR of ≥8.3 years = 3.88; P for trend by duration < 0.01).
Conclusion
Effectiveness of administering 4 doses of pertussis vaccine during infancy decreases with time passed since the fourth dose. This regimen does not protect school-aged children against pertussis.
... The overall attack rate was 15% (70/467), but it increased to 32% (16/50) among those who had received the last dose at least 9 years previously (RR = 1.39; 95% CI: 0.47-4.05). Results suggest that the decay of immunity started about 5 years after the last dose of pertussis vaccine and the RR increased with the time elapsed since the last vaccine dose [71]. ...
... According to Sin et al., the recommendation for the first booster vaccination between 9 and 17 years of age in place in Germany until 2006 was insufficient to protect school-aged children from pertussis. In this outbreak, the majority of cases could have been prevented by an early booster dose of a pertussis-containing vaccine [71]. ...
Background:
Pertussis is an acute infectious illness, caused by the bacteria Bordetella pertussis and commonly known as "whooping cough". Waning immunity after vaccination or after natural infection contributes significantly to the increasing incidence rates in adolescents and adults. Prevention of pertussis in industrialized countries is mainly based on immunization with acellular vaccines in combination with other antigens. A booster dose with an adult-formulation tetanus-diphtheria toxoid and acellular pertussis vaccine (Tdap) is now recommended for all adolescents by several countries, and replacement of the decennial Td dose with a single or more doses of Tdap is recommended for adults.
Objective:
Our review aims at describing the current knowledge on the impact of acellular pertussis vaccination in adolescents and adults, with particular focus on specific risk groups: adolescents, pregnant women and their newborns, and health care workers (HCWs), and secondly at suggesting possible immunization strategies.
Methods:
Data were retrieved by searches of Pubmed, references, from relevant articles and open-access websites.
Results:
In countries where an adolescent booster dose was adopted, a certain decrease of incidence rates was observed. No serologic correlate of protection after immunization exists, but subjects with high antibody levels against pertussis antigens are less likely to develop the disease. Tdap vaccine was demonstrated to induce antibodies to pertussis antigens exceeding those associated with efficacy in infants, in both adolescents and adults. Tdap use in pregnant women seems to be safe and might represent a useful tool in order to prevent pertussis cases in the first months of life. Neonatal immunization with monovalent acellular pertussis vaccine can efficiently prime T and B cells and act as a basis for future immune responses. Cocooning strategies involving all those surrounding newborns have started to be implemented. Their impact on infant pertussis cases will be evaluated in the coming years. Coverage in HCWs should be increased, given their important role in pertussis transmission in health care settings.
Conclusions:
Despite the more recent position paper of WHO gives priority to infant and childhood vaccination against pertussis and leaves adolescent, adult and risk group immunization as an option for the future, data are quickly accumulating to support the need to consider pertussis vaccination as a crucial preventative intervention even in adolescents and special risk groups.
... An outbreak in California during 2010 accounted for 14.5% of reported cases [1,3]. Between 2000 and 2009, the majority of cases reported in the USA have occurred in adolescents and adults, consistent with waning protection after childhood vaccination and suboptimal coverage rates of booster doses of combined tetanus and reduced diphtheria toxoids and acellular pertussis vaccine [Tdap] in adolescents and adults34567. Although the reported proportion of adolescents receiving Tdap has increased since vaccine licensure in 2005, only 56% of adolescents had received a dose of Tdap vaccine by 2009 [8]. ...
... These results suggest that considerable numbers of adolescents and adults are susceptible to pertussis as a result of waning immunity after childhood immunization. Susceptibility to the bacterium may be a major factor in the resurgence of pertussis in the USA and other countries as a result of low vaccination coverage of adolescents with acellular pertussis vaccine boosters34567 . Tdap vaccine used in these studies induced excellent antibody responses to all antigens in both adolescents and adults. ...
Persistence of antibodies after a single dose of Tdap vaccine (tetanus, diphtheria, and 5-component acellular pertussis vaccine) was evaluated in a follow-up study of adolescents (N=324) and adults (N=644) who had received Tdap in earlier clinical trials. Outcome measures were seroprotection (tetanus and diphtheria) or seropositivity (pertussis) and geometric mean concentrations. Humoral immune responses to all antigens were robust 1 month after initial immunization, decreased at subsequent measurements, but continued to exceed pre-immunization levels 1, 3, 5, and 10 years later. Protective levels of diphtheria and tetanus antitoxin persisted in 99.3% of adolescents 10 years after a booster dose of Tdap. Seropositivity to 1 or more pertussis antigens also persisted in most adolescents for 10 years. Although tetanus antitoxin responses were similar in adults to those observed in adolescents, diphtheria antitoxin titers were lower, reflecting the fact that a smaller proportion of adults had received diphtheria toxoid in the previous 10 years compared to adolescents. These data will contribute to the selection of the optimal interval for repeat doses of Tdap.
... Pertussis is an acute respiratory infectious disease caused by the bacterium Bordetella pertussis. Despite widespread immunization with pertussis vaccines, many countries still report outbreaks [1][2][3][4]. The World Health Organization estimates that in 2008 there were 195,000 deaths from whooping cough worldwide and most of deaths occurred in the developing countries [5]. ...
... In order to characterize the immunogenicity of r-Prn, recombinant and native antigens were formulated with Al(OH) 3 and injected to NIH mice. All animals that were immunized with both Prn showed strong serum IgG antibody responses when compared to the control group. ...
... Between 31% (2017) and 36% (2013/2015/2020) of all reported cases occurred in OA; the proportion of cases reported in OA was 0.4 pp higher at the end of the analytical period (2020) than at the start (2013) (Supplementary Fig. S1) [52]. Germany employed passive, populationbased surveillance with case-based reporting, which became mandatory in 2013 [12,22,53]. Reporting included cases that were only clinically and/or epidemiologically confirmed; however, for the purpose of this analysis, only laboratory-confirmed clinical cases were considered. ...
Introduction:
Following the introduction of pertussis vaccination during infancy, the age-related demographics of pertussis epidemiology have changed.
Methods:
To better understand the pertussis burden (defined here as number of cases and/or incidence rate [IR]) among older adults (OA; at least 50 years of age) in Europe, we collected data on the reported number of cases and IR in this population in Denmark, England and Scotland, Finland, Germany, the Netherlands, Norway and Sweden from 2010 to 2020. Additionally, we collected contextual epidemiological information on surveillance systems, case definitions, laboratory diagnostics and vaccination approaches.
Results:
We observed large heterogeneity in the burden among OA between countries: annual IRs ranged from 0.4 (England, 2010) to 54.5 (Norway, 2011) per 100,000 population; 9% (Denmark, 2010) to 45% (England, 2017) of all reported cases occurred in OA. No clear impact of changes in contextual epidemiological information or common trends between countries could be observed, highlighting the need for standardised pertussis surveillance programmes across Europe. The epidemiological trends observed in OA were similar to those observed in 0-4-year-olds.
Conclusion:
This analysis showed that B. pertussis continues to circulate among OA in Europe, suggesting that current vaccination strategies are insufficient to decrease the disease burden in all age groups. This may indicate that improved monitoring of pertussis in OA and booster vaccination throughout adulthood are necessary to control the total pertussis burden.
... This is different than during most outbreak investigations, when only symptomatic individuals are swabbed. Our findings demonstrate a rate of confirmed symptomatic disease (AR: 14%) similar to those previously reported in other pertussis school outbreaks [17,18]. When including all symptomatic (AR: 30%) and asymptomatic cases (AR: 18%), the rate more than tripled (AR: 48%). ...
On 1 May 2018, a pertussis outbreak was declared and widespread vaccination recommended at an all-female secondary boarding school in southern England. We conducted a retrospective cohort study to determine the extent of pertussis transmission and identify risk factors in this semi-closed population. Of 504 students and staff assessed before post-exposure vaccination, 48% (n = 240) had evidence of pertussis. A sub-analysis of 409 students found that both residential dormitory (p = 0.05) and school year (p = 0.03) were associated with pertussis, with odds decreasing by 11% for each increase in school year (95% confidence interval: 0.7-20.2). Odds of pertussis were 1.7 times higher in those assumed to have received acellular vaccines for their primary course compared with those assumed to have received whole-cell vaccines (based on date of birth), although this difference was not significant (p = 0.12). Our findings support the need for timely, widespread vaccination following identification of cases among adolescents in a semi-closed United Kingdom (UK) setting and to review the evidence for the introduction of an adolescent pertussis booster to the UK routine vaccination programme.
... In an attempt to improve the control of pertussis, a number of countries have included additional booster doses beyond preschool [3]. However, despite offering booster vaccinations before school entry and in adolescence, outbreaks in primary schools have been noted in such countries, including China, Germany and the United States [4][5][6]. ...
In March 2019, a pertussis outbreak occurred in children in a junior school (7–11 years) in England who had been offered pertussis-containing booster vaccine at 40 months of age. In a case–control investigation, we assessed the extent of transmission and any difference in protection afforded to those who had previously received a booster 3- or 5-component acellular pertussis vaccine (aP). We took oral fluid specimens from the students to determine IgG antibodies against pertussis toxin (anti-PT). Parents of students attending the school were sent a questionnaire on pertussis symptoms and vaccination status was retrieved from general practitioner records for all students. Of 381 students, 134 (35.2%) were classified as pertussis cases, 133 by demonstration of significant anti-PT IgG titres and one clinically. There was no significant difference in the risk of pertussis between students receiving 3-component (33.7%) or 5-component (32.3%) aP boosters. However, pertussis infection differed significantly in school year 4, with 22.9%, 50.0%, 23.7% and 38.1% pertussis cases in years 3, 4, 5 and 6, respectively. The proportion of students with incomplete vaccinations recorded was higher than the proportion of those not covered according to the national reported coverage, possibly contributing to sustained transmission within the school.
... The introduction of vaccination has reduced the incidence of whopping cough. However, the risk of outbreaks is still a public health concern since several countries have reported an increased incidence of pertussis (2,(7)(8)(9)(10). A possible explanation for this is the expansion of strains antigenically distinct from those in the vaccines or a higher waning of immunity among people vaccinated with aP than among those vaccinated with wP. ...
... In the analyses, continuous variables except for age and the number of family members were re-categorized into two levels according to the median value of the distribution of controls. Age was re-categorized into three levels, based on the age at which most children completed DTaP vaccination (i.e., 2 years) and the age when the effects of DTaP vaccination could be continued (i.e., 10 years) [4][5][6][7][8][9][10]. Regarding the number of family members, a three-level category was used when considering the family structure. ...
When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis.
After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR = 0.11, 95% CI, 0.01–0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR = 0.07, 95%CI, 0.01–0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR = 5.67) and those with a recent contact with a lasting cough (OR = 4.12).
When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique.
... The majority of pertussis cases could be avoided with the introduction of early booster doses in adolescence and decennial boosters in adulthood. [64][65][66] Therefore, even in AH subjects, previously vaccinated with a primary cycle, one booster dose with dTap is recommended, while in na€ ıve subjects or subjects who are not fully vaccinated, the entire cycle should be repeated. Moreover, for AH adult subjects decennial booster doses with dTap vaccines are recommended, as for the general population. ...
Asplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infectious diseases (IDs) incidence in AH subjects can be reduced by preventive measures such as vaccination. The aim of our work is to provide updated recommendations on prevention of infectious diseases in AH adult patients, and to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation. A systematic literature review on evidence based measures for the prevention of IDs in adult AH patients was performed in 2015. Updated recommendations on available vaccines were consequently provided. Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended and should be administered at least 2 weeks before surgery in elective cases or at least 2 weeks after the surgical intervention in emergency cases. In subjects without evidence of immunity, 2 doses of live attenuated vaccines against measles-mumps-rubella and varicella should be administered 4–8 weeks apart from each other; a booster dose of tetanus, diphtheria and pertussis vaccine should be administered also to subjects fully vaccinated, and a 3-dose primary vaccination series is recommended in AH subjects with unknown or incomplete vaccination series (as in healthy people). Evidence based prevention data support the above recommendations to reduce the risk of infection in AH individuals.
... This shift in the burden of disease has been attributed, in part, to the fact that immunity to pertussis is not lifelong, whether after natural infection or vaccination [4]. Multiple observational studies have indicated that the immunity conferred by childhood acellular pertussis (aP) vaccines rapidly wanes in the first few years after completion of the childhood series [5][6][7][8][9]. In contrast, receipt of even a single dose of whole-cell pertussis (wP) vaccine as part of the childhood series confers more durable protection against pertussis [10,11]. ...
Background:
Acellular (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed.
Methods:
We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within three years after completion (>3 doses) of a primary series of a currently available aP or wP formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group (CHERG). We determined overall effect sizes using random effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type.
Results:
Meta-analysis of two aP vaccine efficacy studies (assessing the three-component GlaxoSmithKline and five-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval (CI), 81-87%). Meta-analysis of three wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Merieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88-97%) (both I(2)=0%).
Conclusions:
Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines.
... 21 A similar situation has also been witnessed in Europe where pertussis is on the rise, and outbreaks are being reported in people of all age groups. [22][23][24][25] Surveillance data from Germany, Netherland, Finland, Russia, France, Switzerland, Italy, Norway, and other European countries reveal pertussis resurgence. 6,20,[26][27][28] Furthermore, pertussis epidemics and outbreaks in vaccinated populations have also been reported from South American and Eastern European countries. ...
Pertussis or whooping cough is a highly infectious, vaccine preventable disease. The incidence of the disease has greatly been reduced since the introduction of the diphtheria, tetanus, pertussis vaccine. Pertussis resurgence has been observed in highly vaccinated populations of Western countries since 1990s. Poor vaccine quality, waning vaccine induced immunity, pathogen adaptation, and enhanced surveillance as well as advancements in diagnostic facilities are some of the reasons considered responsible for the increased reporting of pertussis cases. Pertussis may have been ignored and unnoticed due to its atypical manifestations in partially immunized population or people with waning immunity. We review the reports of pertussis resurgence from different countries and attempt to investigate reasons behind the reappearance of the disease. Pertussis is still an under reported disease and the available data from the developing countries is not a true picture of the story. Therefore, developing countries need to improve their surveillance systems.
... There has been gradual increase after a nadir in 1976, and substantial increases since 2000. 2 The waning of vaccine-acquired immunity and decreased opportunities for boosting of immunity are considered as main reasons for the reemergence of pertussis. [2][3][4] of 18 multiple choice questions included respondents' demographic characteristics, perceived risk of infant pertussis, concern about the safety of Tdap, access to information about Tdap, possible barriers about Tdap, and, finally, the most important factor influencing a woman's decision to accept or decline the vaccine. ...
The adult tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine has been introduced in order to provide individual protection and reduce the risk of transmitting pertussis to infants. We assessed the knowledge and acceptability of the Tdap vaccine around pregnancy.
This study was a cross-sectional survey of women of childbearing age (20-45 years) who visited obstetrics and gynecologic units of primary, secondary, or tertiary hospitals. They were asked to fill in a questionnaire assessing their knowledge, attitudes, and acceptability of Tdap.
The questionnaire was completed by 308 women; 293 (95.1%) had not received information from doctors about Tdap, and 250 (81.2%) did not know about the need for vaccination. A significantly important factor related to subjects' intention to be vaccinated, identified by stepwise multiple logistic regression, was the knowledge (OR 13.5, CI 3.92-46.33) that adult Tdap is effective in preventing pertussis for infants aged 0-6 months. Additionally, 276 (89.6%) considered the recommendation of obstetric doctors as the most influencing factor about Tdap vaccination.
In Korea, most women of childbearing age seem to be neither recommended nor adequately informed about the vaccination, although our population was not a nationwide representative sample. Information given by healthcare workers may be critical for improving awareness and preventing pertussis.
... The introduction of vaccination has reduced the incidence of whopping cough. However, the risk of outbreaks is still a public health concern since several countries have reported an increased incidence of pertussis (2,(7)(8)(9)(10). A possible explanation for this is the expansion of strains antigenically distinct from those in the vaccines or a higher waning of immunity among people vaccinated with aP than among those vaccinated with wP. ...
Despite the reduction in incidence after vaccination, pertussis disease is still considered a public health problem worldwide,
mainly due to recent and potential new outbreaks. We report here the complete genome of the Bordetella pertussis Butantan strain used in the Brazilian National Immunization Program as a whole-cell pertussis antigen to compose vaccines
such as DTwP (diphtheria, tetanus, and whole-cell pertussis).
... This may be explained by waning immunity, as suggested by other reports. [22][23][24] From 2003 onwards, the age distribution of affected cases show highest incidence in infants aged <1 y. Before 2003, the incidence according to age groups showed a different pattern. ...
In Catalonia, pertussis outbreaks must be reported to the Department of Health. This study analyzed pertussis outbreaks between 1997 and 2010 in general and according to the characteristics of the index cases. The outbreak rate, hospitalization rate and incidence of associated cases and their 95%CI were calculated. Index cases were classified in two groups according to age (<15 years and ≥15 years) and the vaccine type received: whole cell vaccine (DTwP) or acellular vaccine (DTaP). During the study period, 230 outbreaks were reported. The outbreak rate was 2.43 × 10⁻⁶ persons-year, and outbreaks ranged from 2 to 32 cases, with a median duration of 18 days. There were 771 associated cases, with an incidence rate of 0.8 × 10⁻⁵ persons-year.
After classifying outbreaks according to the age of the index case, 126 outbreaks (1.3 × 10⁻⁶ persons-year) had an index case aged <15 y and 87 (0.87 × 10⁻⁶ person-year) had an index case aged ≥15 y (RR = 1.44, 95%CI 1.10–1.90; P = 0.007).
Between 2003 and 2010, after the introduction of the acellular vaccine, the index case was vaccinated with DTwP vaccine in 25 outbreaks (0.43 × 10⁻⁶ persons-year) and with DTaP vaccine in 32 outbreaks (0.55 × 10⁻⁶ person-year) (RR = 0.78, 95%CI 0.46–1.31; P = 0.35).
Of cases, 37.2% were correctly vaccinated, suggesting waning immunity of pertussis vaccine protection and endogenous circulation of pertussis. A greater number of outbreaks had an index case aged <15 y. No changes in the disease incidence, associated cases and hospitalization rate were observed after the introduction of DTaP.
... 21 A similar situation has also been witnessed in Europe where pertussis is on the rise, and outbreaks are being reported in people of all age groups. [22][23][24][25] Surveillance data from Germany, Netherland, Finland, Russia, France, Switzerland, Italy, Norway, and other European countries reveal pertussis resurgence. 6,20,[26][27][28] Furthermore, pertussis epidemics and outbreaks in vaccinated populations have also been reported from South American and Eastern European countries. ...
يعد السعال الديكي أو الشاهوق من األمراض املعدية التي ميكن
الوقاية منها أو توقيها بالتطعيم. انخفض ظهور املرض بشدة منذ
ظهور لقاح اخلناق، والكزاز، والشاهوق DTP. لوحظ بكثرة إعادة
ظهور املرض لدى العديد من األشخاص املطعمني في الدول الغربية
منذ 1990م. بعض األسباب التي كانت مسؤولة بشكل رئيسي على
حاالت السعال الديكي كانت ضعف جودة اللقاح املقدم، وانخفاض
املناعة الناجتة بعد التطعيم، وتالؤم املرض، وتعزيز نظام املراقبة، وتطور
التشخيص في املرافق الصحية. أن تشخيص السعال الديكي مهمل
وقد ال يالحظ نظراً ً للمظاهر الشاذة في األشخاص احملصنني جزئيا
أو األشخاص ضعيفي املناعة. في هذا التقرير نستعرض مراجعات
بخصوص عودة السعال الديكي من دول عديدة ومحاولة التحقق
من األسباب خلف إعادة ظهور املرض. كما تركز على احلقيقة أن
السعال الديكي من األمراض املعدية غير املبلغ عنها إلى اآلن. كما
أن اإلحصائيات املقدمة من الدول النامية ال تعكس الصورة احلقيقية
للمرض. لذلك، حتتاج هذه الدول إلى تطوير نظام املراقبة.
Pertussis or whooping cough is a highly infectious,
vaccine preventable disease. The incidence of the disease
has greatly been reduced since the introduction of the
diphtheria and tetanus toxoids and pertussis (DTP)
vaccine. Pertussis resurgence has been observed in highly
vaccinated populations of Western countries since 1990s.
Poor vaccine quality, waning vaccine induced immunity,
pathogen adaptation, and enhanced surveillance as
well as advancements in diagnostic facilities are some
of the reasons considered responsible for the increased
reporting of pertussis cases. Pertussis may have been
ignored and unnoticed due to its atypical manifestations
in partially immunized population or people with waning
immunity. We review the reports of pertussis resurgence
from different countries and attempt to investigate
reasons behind the reappearance of the disease. Pertussis
is still an under reported disease and the available data
from the developing countries is not a true picture of the
story. Therefore, developing countries need to improve
their surveillance systems.
... This is in accordance with many seroepidemiologic studies carried out in industrialized countries which have described a waning antibody response 18 months-5 years after immunization [12][13][14]. ...
... In addition, a role of Th17 cells in prevention of carriage is suspected [53]. The cause of resurgent outbreaks of pertussis is unknown, but high on the list of suspects is waning antibody after acellular vaccines, perhaps because of a Th response that is Th2-directed rather than the Th1 type provided by whole cell vaccines [54][55][56][57][58]. ...
In several prior articles I have attempted to analyze and simplify the subject of immunological functions induced by vaccination
that correlate with protection against later exposure to pathogens. Other authors have also written on the subject, and recently
we jointly proposed terminology to bring some semantic clarity to the field. The generalization that vaccine-induced antibodies
prevent acquisition whereas cellular immune functions clear infection still holds true, but that simple distinction becomes
blurred in many instances. Specific antibody and cellular responses are multiple and redundant, so that vaccines for some
pathogens protect through more than 1 immune function. Thus, this article aims in the direction opposite to simplicity to
depict the complexity of correlates, or rather the complexity of mechanistic immune functions that contribute to protection.
Nonmechanistic correlates that are practically useful but not truly protective will be mentioned in passing.
... The increased responses in children above 3–4 years to PT could be due to high human contact levels in this age group (household members, schooling, greater range of social interaction, etc.). In various outbreaks across Europe and the USA transmission between schoolmates was clearly demonstrated, emphasizing the role of older children in the transmission of pertussis to school- mates [26], [27]. The impact of circulating bacteria in the maintenance of immune memory to pertussis and consequently in preventing transmission or clinical disease remains nonetheless to be studied in more detail in our setting. ...
Pertussis, also known as whooping cough, is a vaccine-preventable respiratory disease caused by Bordetella pertussis infection, against which Senegalese children are immunized with the diphtheria-tetanus-whole cell pertussis vaccine (DTwP). Seroepidemiology of pertussis has been widely described in industrialized countries, but rare are the studies referring to it in developing countries.
We conducted a longitudinal survey in Northern Senegal to investigate the epidemiology of B. pertussis by evaluating the IgG antibody (Ab) response against pertussis toxin (PT). A cohort of 410 children aged 1 to 9 from five villages in the Middle Senegal River Valley were followed-up for 18 months. During that period, five visits were made to assess the immunological status of the children.
PT-specific IgG responses were significantly different according to age. Until the age of 3, there was a decrease in the Ab response, which then increased in the older groups. Assessment of IgG antibodies to PT (IgG-PT) suggested evidence of recent exposures to the pathogen. Surprisingly, in one of the five villages the average Ab response to PT was very low at all ages during the first 6 months of the study. At the third visit, IgG-PT concentrations peaked to very high levels, to slightly decline at the end of the survey. This indicates an outbreak of B. pertussis, whereas in the other villages a pertussis endemic profile could be observed.
Pertussis is endemic in Northern Senegal despite the introduction of vaccination. The circulation of the bacteria seems to differ between geographic locations and over time. A more complete understanding of the epidemiology of pertussis and its environmental determinants could provide information to adapt vaccination programs.
... The mean and median time between the date of the third vaccination and the diagnosis of pertussis were 5.0 and 5.3 years indicating waning immunity after about 5 years. This is similar to other studies of the duration of immunity induced by other acellular pertussis vaccines with more than one component [28][29][30]. ...
After 16 years of no vaccination against pertussis in Sweden, mass vaccination of infants and catch-up vaccination of children up to 10 years with a monocomponent pertussis toxoid vaccine was performed in the Greater Gothenburg area of Sweden between 1995 and 1999. At the end of the project in February 1999, 56% of all 10 year old children born in the Greater Gothenburg area had received 3 doses of the pertussis toxoid. No booster doses were given. This led to a temporary almost complete elimination of the disease. The aim of the present study was to follow the incidence of pertussis after end of the mass vaccination project (1999-2009) as it is reflected by laboratory verified cases (cultures and/or PCR) and pertussis hospitalizations. A reemergence of pertussis was seen from the end of 1999 with a peak in 2004 followed by a decrease when booster doses to both 6 and 10 year old children were introduced in 2005-2006. From July 1, 1999 through December 31, 2009 a total of 1973 cases were diagnosed with culture or PCR. The disease was prevalent in all age groups. The highest documented incidence was seen in infants younger than 12 months. 450 patients with verified pertussis had received 3 doses of the pertussis toxoid vaccine in the mass vaccination project and some other trials (comprising a total of 69,423 children). The mean time from the last dose to the laboratory verification of pertussis was 5 years in these 450 cases. There were 128 hospitalizations, 106 of which were in infants. In conclusion, pertussis is still not eliminated from the area. Booster doses are needed but the numbers and optimal timing are not known.
... This waning of immunity has led to a recommendation in many countries for a vaccine booster dose for adolescents and adults. The duration of immunity is estimated to range from seven to 20 years after infection with B. pertussis and 4-12 years after vaccination with whole or acellular pertussis vaccine678, thus making adolescents and adults more susceptible to pertussis disease. Waning immunity and the subsequent increase in disease is associated with considerable morbidity and economical costs and increases the probability of transmission of pertussis infection to vulnerable children. ...
We report a community pertussis outbreak that occurred in a small town located in the northwest of Ireland. Epidemiological investigations suggest that waning immunity and the absence of a booster dose during the second year of life could have contributed to the outbreak. The report also highlights the need to reinforce the surveillance of pertussis in Ireland and especially to improve the clinical and laboratory diagnosis of cases.
... In fact, it is well documented that the disease has re-emerged among adolescents and that the increasing circulation of Bordetella is a frequent cause of pertussis breakthroughs in schools. Moreover, adolescents could be a source of infection for unvaccinated siblings [42]. In Italy pertussis coverage among adolescents is consistently low, even though different between regions. ...
... Despite continuous high immunization coverage rate among infants and children, pertussis has remained endemic and the incidence of reported pertussis disease has gradually increased after reaching a nadir in 1976 [2]. Waning of vaccine-acquired immunity and decreased opportunities for boosting of immunity have been cited as some of the possible reasons for reemergence of pertussis in adolescents and adults [2][3][4]. ...
We conducted surveys to determine factors influencing women's decisions to accept or decline postpartum pertussis (Tdap) vaccination. Survey response rate among eligible individuals was 97%. Of respondents, 53% accepted and 47% declined postpartum Tdap. Women, who declined vaccination were more likely to rate maternal or infant risk of exposure to pertussis as low, report that they did not trust information about postpartum pertussis vaccination, and report being very concerned about the safety of the vaccine. Awareness about pertussis, its risk to infants, and prevention via vaccination need to be further increased among women of child-bearing age, particularly pregnant women.
... Clusters and outbreaks of pertussis among adults within occupational settings have been documented among health care workers (HCWs), soldiers, office workers, inmates and students [1][2][3][4][5][6]. The risk and consequences of such transmission within the health care setting is of concern, particularly when exposed patients fall within vulnerable groups [7]. ...
We describe an outbreak of pertussis with transmission between health care workers (HCWs) in a hospital oncology department and a patient identified as a possible source. Three of the four HCWs testing positive for pertusssis had received primary immunization as children, consistent with waning immunity into adulthood. The fourth health care worker was unimmunized. No evidence of onward nosocomial acquisition within the patient group was found; however, transmission within the household of one health care worker was identified. Countries differ in their approach to protecting health care staff and patients from occupational and nosocomial pertussis infection with immunization recommended for some HCWs in some countries. Surveillance for pertussis in the UK and response to suspected or confirmed cases requires further development.
Introduction. Current serological diagnosis of pertussis is usually performed by ELISA, which is typically performed in larger diagnostic or reference laboratories, requires trained staff, and due to sample batching may have longer turnaround times.
Hypothesis and Aim. A rapid point-of-care (POC) assay for pertussis serology would aid in both the diagnosis and surveillance of the disease.
Methodology. A quantitative lateral flow (LF)-based immunoassay with fluorescent Eu-nanoparticle reporters was developed for the detection of anti-pertussis toxin (PT) and adenylate cyclase toxin (ACT) antibodies from oral fluid samples (N=100), from suspected pertussis cases with respiratory symptoms.
Results. LF assay results were compared to those obtained with anti-PT
IgG oral fluid ELISA. For an ELISA cut-off value of 50 arbitrary units, the overall agreement between the assays was 91/100 (91 %), the sensitivity was 63/70 (90 %) and the specificity was 28/30 (93 %). No ACT-specific antibodies were detected from oral fluid samples; however, the signal readout positively
correlated to those patients with high anti-PT IgG antibodies.
Conclusion. The developed LF assay was a specific, sensitive and rapid test for serological diagnosis of pertussis with anti-PT antibodies and is a suitable POC test using oral fluid samples.
Background
Despite high pertussis vaccination coverage and significant decrease of pertussis since the adoption of the Expanded Programme on Immunization (1978), increased pertussis incidence has been reported in China from 2013 to 2017. This study aimed at evaluating the immune response to pertussis among vaccinated children and beyond in China.
Methods
The study recruited 2 144 healthy subjects. Serum IgG antibodies against pertussis toxin (anti-PT IgG) were measured by ELISA. Anti-PT IgG concentration (GMC), seropositivity rate (GMC ≥ 40 IU/ml), and recent infection rate (GMC > 100 IU/ml) were calculated. Participants ≤ 2 years-old were further stratified by vaccination schedule intervals and participants ≤ 6 years-old by vaccine used (Domestic DTaP or DTaP-IPV//PRP ~ T (Pentaxim, SP)).
Results
Among 0–6-year-olds, the anti-PT IgG GMC was 5.99 IU/ml (95%CI 5.39–6.67). The GMC increased in accordance with the primary vaccination series (4–6 months) and the toddler booster (18–23 months), and continuously declined thereafter to its nadir at 6 years-old [3.72 IU/ml (95%CI 2.91–4.77)]. GMCs were markedly higher in those vaccinated with DTaP-IPV/PRP ~ T compared to DTaP. In individuals > 6 years-old, the GMC was 5.67 IU/ml (95%CI 5.36–6.00), the seropositivity rate was 6.7% (95%CI 5.5–7.9) and the recent infection rate was 1.2% (95%CI 0.7–1.7). The seropositivity rates increased from 6 years-old and peaked at 9 years-old (10.3% [95%CI 0.7–19.8]).
Conclusions
Vaccination against pertussis increases anti-PT IgG, but wanes over time. The sero-estimated infection rates increase from school age and peak at about 9 years-old. These results support the addition of a booster of pertussis vaccine at preschool age.
To gain insights into the current Japanese pertussis immunization schedule, we examined the distributions of antibody titers and avidities to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in 460 Japanese healthy subjects (aged 1–60 years) based on age category. Our avidity enzyme-linked immunosorbent assays revealed that young children aged 1–2 years, which corresponded to ages after receiving primary and/or booster pertussis vaccinations, had relatively high-avidity anti-PT IgG (mean avidity index [AI], 40.5%) compared with other age groups (AI, 26.5–31.9%); however, they had relatively low-avidity anti-FHA IgG (AI, 41.8%). In contrast, children aged 3–6 years had both low-avidity anti-PT IgG (AI, 26.5%) and low-avidity anti-FHA IgG (AI, 40.4%). A significant age-related difference in anti-PT IgG avidity was observed between children aged 1–2 years and 3–6 years (P < 0.05); however, the difference in anti-FHA IgG avidity was not significant. The anti-PT IgG avidity was positively correlated with the antibody titer, especially among children aged 1–15 years (r s = 0.508–0.685; P < 0.01), indicating that the avidity of vaccine-induced anti-PT IgG decreases with decreasing IgG antibody titer to PT. Our findings strongly suggest that vaccine-induced anti-PT IgG avidity rapidly wanes after vaccination, but this is not observed for anti-FHA IgG avidity. Because children aged 3–6 years have both low-quantity and low-quality antibodies against PT, an additional booster vaccination with acellular pertussis vaccines is required for such children in Japan.
Background
A big pertussis outbreak occurred in a primary school with high vaccination coverage in northern China. An investigation was carried out in order to calculate the attack rate and identify the risk factors.
Methods
Between May 12 and July 29, an investigation was carried out in the primary school, which included 383 students and 27 teachers. Three definitions were used to distinguish the cases: confirmed, epidemiologically linked and suspected cases. A total of 232 blood samples were collected and examined by ELISA among healthy children in another primary school.
Results
A total of 138 suspected pertussis cases were counted, of which 116 students were confirmed. The attack rate among students was as high as 30.29%. The pertussis outbreak lasted 88 days, and had quaternary cases of transmission. Migrant children were almost four times as likely to catch the disease as local children (p = 0.005). In addition, students who had received the last dose of pertussis vaccine more than 4 years prior were three times more likely of becoming ill than those less than 4 years (p = 0.006). The average level of antibodies to pertussis was 30.99 IU/mL among healthy children. No statistically significant difference was observed between DTaP and DTwP (p = 0.843).
Conclusions
This pertussis outbreak in a primary school with high vaccination coverage was an evidence of the pertussis resurgence in China. The major risk factor we identified was the waning of immunity in the years after pertussis vaccination. Booster vaccination for students should be given.
Whooping cough is a highly contagious, acute respiratory disease, caused by the Gram-negative bacterium Bordetella pertussis (Bp). Despite the introduction and widespread use of vaccines starting in the 1950s pertussis cases continue to be reported, with a significant global impact. The role of specific virulence factors in disease and the immune mechanisms associated with protection following natural infection or vaccination are still not completely understood.
The recently-developed baboon model of clinical pertussis provides a valuable tool for the study of pertussis. Baboons infected with B. pertussis exhibit all of the manifestations of human pertussis including paroxysmal coughing, mucus production, leukocytosis and transmission. The establishment of this model provides the opportunity to address unanswered questions about the natural progression of this disease and host responses to infection and vaccination in a very relevant model.
In this review, we present an overview of our knowledge of pertussis along with recent advances resulting from use of the baboon model. Remaining questions and future research directions are discussed. We hope that the knowledge gained through use of the baboon model of pertussis and clinical studies will allow the development of more efficacious vaccines, conferring long lasting protection against disease and transmission.
Objectives:
Despite the availability of vaccines and the existence of public vaccination recommendations, outbreaks of vaccine-preventable childhood diseases still cause public health debate. The objective of this systematic review was to provide an overview of the current epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany.
Methods:
We systematically reviewed studies published since 2000. The literature search was conducted using PubMed and EMBASE. Also, we used German notification data to give an up-to-date overview of the epidemiology of the four diseases under consideration.
Results:
Thirty-six studies were included in our review. Results suggest that there is still considerable morbidity due to childhood diseases in Germany. Studies providing cost estimates are scarce. Comparative analyses of different data sources (notification data vs. claims data) revealed a potential underestimation of incidence estimates when using notification data. Furthermore, several studies showed regional differences in incidence of some of the diseases under consideration.
Conclusions:
Our findings underline the need for improved vaccination and communication strategies targeting all susceptible age and risk groups on a national and local level.
In 2008, the number of pertussis cases increased substantially among Japanese adolescents, despite high coverage with acellular pertussis vaccine (DTaP). This study examined the effectiveness of DTaP vaccine in the routine immunization program in Japan. Between April 2009 and October 2012, we conducted a multicenter, case-control study, and compared the history of DTaP vaccination between 55 newly diagnosed pertussis cases and 90 age- and sex-matched controls. DTaP vaccine history was obtained by a self-administered questionnaire completed by their parents or guardians. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. DTaP vaccination of ≥1 dose revealed a significantly lower OR for pertussis (OR=0.20, 95%CI, 0.04-0.97), and the OR of complete vaccination (4 doses) was 0.22 (0.04-1.05). Even after limiting subjects to those whose vaccination status could be confirmed by the immunization records, the negative associations were observed. The decreasing ORs of 4-dose vaccinees remained, even among subjects who had received the fourth dose ≥9.2 years earlier (OR=0.11, 95%CI, 0.01-1.02). In conclusion, DTaP vaccination had a preventive effect for pertussis. Effectiveness was observed even 9 or more years after the final dose.
Copyright © 2015. Published by Elsevier Ltd.
An understanding of antibody persistence elicited by combined tetanus, diphtheria, 5-component acellular pertussis and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare safety and immunogenicity in adolescents of Tdap-IPV coadministered with HepB to sequential administration and evaluate humoral immunity 3, 5, and 10 years after Tdap-IPV vaccination. This phase II randomized, controlled, open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n=145) received Tdap-IPV followed by a HepB dose one month later; Group 2 (n=135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/mL for diphtheria and tetanus; ≥1:8 dilution for poliovirus (serotypes 1, 2, 3); and ≥10 mIU/mL for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (≥lower limit of quantitation) and 72.7%-95.8% had 4-fold increases in pertussis antibodies 1 month post-vaccination. At 10 years postvaccination, remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/mL for diphtheria and tetanus, ≥1:8 for all 3 poliovirus serotypes, and 74.1%-98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between groups. These results support coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after adolescent booster vaccination.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Pertussis is increasing due to multiple factors including increasing awareness by clinicians, decreased effectiveness of vaccines, and improved testing. While Bordetella pertussis is the causative agent of pertussis other Bordetella species such as B. parapertussis, and B. holmesii, have been associated with pertussis-like illness. Laboratory diagnosis is made using various tests with molecular methods supplanting culture due to increased sensitivity. Serology is useful but standardized methods that are needed. The targets used for molecular detection are varied and have differing sensitivities and specificities. Laboratorians must consider if differentiation of various Bordetella species is necessary when choosing an amplified testing approach.
We evaluated whether the results of diagnostic polymerase chain reaction (PCR) testing combined with time since last vaccine dose could be used to monitor the effectiveness of acellular pertussis vaccines. In 258 consecutive nasopharyngeal swabs from children and adolescents with typical pertussis symptoms, 80 were positive and 178 were negative in PCR for Bordetella pertussis DNA (IS 481). Time since last vaccine dose was available for 152 patients, of which 120 were fully immunised. Among the fully vaccinated patients, the median age of 41 PCR-positive patients was 8.4 years (range 0.9-12.3) and that of 79 PCR-negative cases was 3.3 years (range 0.4-14.1) (p < 0.01). The median time since last pertussis vaccine dose was 6.05 years [95 % confidence interval (CI): 0.5-10.9] in PCR-positive cases and 2.22 years (95 % CI: 0.04-9.23) in PCR-negative cases (p < 0.001). The use of diagnostic PCR results from pertussis cases together with time since last vaccine dose permits estimates of the duration of protection after vaccination with acellular pertussis vaccines that are in keeping with more complex studies.
Bordetella pertussis is the causative agent of pertussis, also called whooping cough or the cough of 100 days. Infection can result in significant morbidity and mortality, particularly in young infants. Prior to the availability of effective vaccines, pertussis was a major cause of childhood disease. With the advent of such vaccines, the incidence of disease declined dramatically into the 1970s. However, pertussis is still present, with peaks occurring every 3 to 5 years, and the number of cases has been increasing in the United States since the 1980s. With recent reports of numerous outbreaks of pertussis, there is heightened interest in the control and diagnosis of the disease. Efforts to increase immunity through vaccination and also to improve the clinical and laboratory diagnosis of the disease are very important. Part I of this two-part article will review a recent outbreak of pertussis that occurred in California and discuss the biology of the genus Bordetella, followed by the clinical presentation of disease and recommendations for recent vaccination protocols and guidelines for diagnosis. Part II of this article will be published in the August 15 issue of this newsletter and will review laboratory methods available for diagnosis, along with their problems and pitfalls.
We deciphered the genome of Yersinia pestis strain 2501, isolated from the Junggar Basin, a newly discovered great gerbil plague focus in Xinjiang, China. The total
length of assembly was 4,597,322 bp, and 4,265 coding sequences were predicted within the genome. It is the first Y. pestis genome from this plague focus.
Bordetella pertussis is the causative agent of pertussis. Here, we report the genome sequence of Bordetella pertussis strain CS, isolated from an infant patient in Beijing and widely used as a vaccine strain for production of an acellular
pertussis vaccine in China.
Pertussis (whooping cough) is a toxic bacterial infection caused mainly by Bordetella pertussis. In mid-January 2006, several cases of pertussis were diagnosed in a military boarding-school. An investigation was carried out at the end of January to identify the risk factors for infection and to evaluate the efficacy of vaccination.
Three definitions were used to distinguish the cases; confirmed biologically, confirmed epidemiologically and suspected cases. The risk factor study was carried out after the exclusion of suspect cases. Vaccine efficacy (VE) was evaluated from a case-control study where only biologically confirmed cases were included. For each case, five controls were matched according to age, sex and class. A logistic regression and a conditional logistic regression were performed for the risk factor study and vaccine efficacy, respectively. Statistical analysis was carried out using Stata 9.2 software.
A total of 206 cases were included, 17 of them biologically confirmed, 66 epidemiologically and 123 suspected cases. The attack rate was 17.8 per 100. Girls were 1.8 times more likely to catch pertussis (p=0.04), pupils in the first year of college, as well as those in high school were at 5 times greater risk of catching pertussis (p=0.008) than those in the second year of college. For pupils who benefited from at least 5 doses, the VE was at 80% when the last dose dated from less than 6 years earlier.
The attack rate observed in our study was similar to those normally seen during epidemics occurring within a community. Vaccine efficacy declined depending on the time lapse since the last vaccination. Since April 2008, the Public Health Authorities have planned to provide pertussis booster vaccinations for children aged 16-18 who missed those for 11-13-year-old, and for adults aged 26-27 and those who have not been vaccinated for more than 10 years.
Panton-Valentine leukocidin (PVL) is a cytotoxin that causes leukocyte destruction and tissue necrosis. It is produced by
fewer than 5% of Staphylococcus aureus strains. A collection of 172 S. aureus strains were screened for PVL genes by polymerase chain reaction amplification. PVL genes were detected in 93% of strains
associated with furunculosis and in 85% of those associated with severe necrotic hemorrhagic pneumonia (all community-acquired).
They were detected in 55% of cellulitis strains, 50% of cutaneous abscess strains, 23% of osteomyelitis strains, and 13% of
finger-pulp-infection strains. PVL genes were not detected in strains responsible for other infections, such as infective
endocarditis, mediastinitis, hospital-acquired pneumonia, urinary tract infection, and enterocolitis, or in those associated
with toxic-shock syndrome. It thus appears that PVL is mainly associated with necrotic lesions involving the skin or mucosa.
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen for which the prevalence, risk factors, and natural history are incompletely understood.
In this prospective observational study, we evaluated 812 US Army soldiers to determine the prevalence of and risk factors for CA-MRSA colonization and the changes in colonization rate over time, as well as to determine the clinical significance of CA-MRSA colonization. Demographic data and swab samples from the nares for S. aureus cultures were obtained from participants at the start of their training and 8-10 weeks later. Over this time period, participants were observed prospectively to monitor for soft-tissue infections. S. aureus isolates were characterized by in vitro examination of antibiotic susceptibilities, mecA confirmation, pulsed-field gel electrophoresis, and Panton-Valentine leukocidin (PVL) gene testing.
At the initial sampling, 24 of the participants (3%) were colonized with CA-MRSA, 9 of whom (38%) developed soft-tissue infections during the study period. In contrast, 229 participants (28%) were colonized with methicillin-susceptible S. aureus (MSSA), 8 (3%) of whom developed clinical infections during the same period (relative risk, 10.7; 95% confidence interval, 4.6-25.2; P<.001). At follow-up culture, the CA-MRSA colonization rate dropped to 1.6% without eradication efforts. Previous antibiotic use was a risk factor for CA-MRSA colonization at the initial sampling (P=.03). PVL genes were detected in 66% of 45 recovered CA-MRSA isolates, including all 9 clinical isolates available for analysis. Of subjects hospitalized, 5 of 6 had PVL-positive CA-MRSA infections.
CA-MRSA colonization with PVL-positive strains was associated with a significant risk of soft-tissue infection, suggesting that CA-MRSA may be more virulent than MSSA. Previous antibiotic use may play a role in CA-MRSA colonization.
Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) is among the strategies recommended by the Society for Healthcare Epidemiology of America for control of nosocomial MRSA infections. Infection control and laboratory personnel desire rapid, sensitive, and inexpensive methods to enhance surveillance activities. A multicenter study was performed to evaluate a new selective and differential chromogenic medium, BBL CHROMagar MRSA (C-MRSA) medium (BD Diagnostics, Sparks, MD), which enables recovery and concomitant identification of MRSA strains directly from nasal swab specimens taken from the anterior nares. Specimens were inoculated to C-MRSA and Trypticase soy agar with 5% sheep blood agar (TSA II, BD Diagnostics). Mauve colonies on C-MRSA at 24 h and 48 h and suspicious colonies on TSA II were confirmed as Staphylococcus aureus by Gram stain morphology and a coagulase test. In addition, the results of C-MRSA were compared to results of susceptibility testing (five different methods) of S. aureus strains isolated on TSA II. A total of 2,015 specimens were inoculated to C-MRSA and TSA II. Three hundred fifty-four S. aureus isolates were recovered; 208 (59%) were oxacillin (methicillin) susceptible and 146 (41%) were oxacillin resistant (MRSA). On C-MRSA, 139/146 or 95.2% of MRSA isolates were recovered, whereas recovery on TSA II was 86.9% (127/146) (P = 0.0027). The overall specificity of C-MRSA was 99.7%. When C-MRSA was compared to each susceptibility testing method, the sensitivity and specificity, respectively, were as follows: oxacillin MIC by broth microdilution, 94.4% and 96.7%; oxacillin screen agar, 94.3% and 96.7%; PBP2' latex agglutination, 93.7% and 98.5%; cefoxitin disk diffusion, 95.0% and 98.1%; and mecA PCR, 95.1% and 98.1%. In this study, C-MRSA was superior to TSA II for recovery of MRSA from surveillance specimens obtained from the anterior nares and was comparable to conventional, rapid, and molecular susceptibility methods for the identification of MRSA isolates.
We evaluated the Phoenix automated microbiology system (BD Diagnostic Systems, Sparks, MD) for the identification (ID) and
antimicrobial susceptibility testing (AST) of challenge and clinical staphylococci and enterococci recovered from patients
in a tertiary-care medical center. In total, 424 isolates were tested: 90 enterococci; 232 Staphylococcus aureus isolates, including 14 vancomycin-intermediate S. aureus isolates; and 102 staphylococci other than S. aureus (non-S. aureus). The Phoenix panels were inoculated according to the manufacturer's instructions. The reference methods for ID comparisons
were conventional biochemicals and cell wall fatty acid analysis with the Sherlock microbial identification system (v 3.1;
MIDI, Inc. Newark, DE). Agar dilution was the reference AST method. The overall rates of agreement for identification to the
genus and the species levels were 99.7% and 99.3%, respectively. All S. aureus isolates and enterococci were correctly identified by the Phoenix panels. For the non-S. aureus staphylococci, there was 98.0% agreement for the ID of 16 different species. The AST results were stratified by organism
group. For S. aureus, the categorical agreement (CA) and essential agreement (EA) were 98.2% and 98.8%, respectively. Three of three very major
errors (VMEs; 1.7%) were with oxacillin. For non-S. aureus staphylococci, the CA, EA, VME, major errors, and minor error rates were 95.7%, 96.8%, 0.7%, 1.7%, and 2.9%, respectively.
The two VMEs were with oxacillin. For the enterococci, there was 100% CA and 99.3% EA. All 36 vancomycin-resistant enterococci
were detected by the Phoenix system. The Phoenix system compares favorably to traditional methods for the ID and AST of staphylococci
and enterococci.
An accurate, practical laboratory test is needed to confirm clinical diagnosis of pertussis in adults during the first 3 symptomatic weeks, when treatment is effective and transmission can be interrupted.
The sensitivity and specificity of single IgA and IgG levels were assessed in a cohort study of a pertussis epidemic in 99 adults in a closed community. Sensitivities were assessed in the sera of 46 laboratory confirmed clinical pertussis cases during the first 3 weeks. Specificities were calculated in sera of 35 asymptomatic controls without clinical symptoms or laboratory confirmed infections from the same community (internal controls). We compared these specificities with the specificities of single IgA and IgG levels in 4275 external controls from a cross-section of the general Dutch population aged 21-79 years who had not coughed for more than 2 weeks in the past year, and without pertussis diagnoses. The study was done in the Netherlands when whole-cell pertussis vaccine was used in the national vaccination programme.
Levels of 24 U/ml for IgA and 27 U/ml for IgG gave sensitivities of 100% and 75%, respectively, in the first 2 weeks, 100% in the third week, and 97% after the fourth week. The levels were reached within 2 days after onset of increase, and remained above these levels for roughly 7.2 and 5.1 months, respectively. Specificity was 82% for IgA and 89% for IgG in the internal controls and 90% in the external controls, respectively.
We suggest levels of 24 U/ml for IgA level and 27 U/ml (= 27 International Units (IU)/ml) for IgG as sensitive, specific, and practical for laboratory confirmation of clinical pertussis in adults in the first 3 weeks of outbreak management.
To evaluate the prevalence of colonization among patients with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection and their household contacts.
Prospective, observational laboratory study of nasal colonization among patients and their household members from September 15, 2004, to February 20, 2006.
A 600-bed, urban, academic medical center.
Fifty-one patients who presented with CA-MRSA infections and 49 household members had cultures of nasal swab specimens performed.
Skin and soft-tissue infections were seen in 50 patients (98%) and 2 household members. Twenty-one (41%) of 51 patients and 10 (20%) of 49 household members were colonized with MRSA. An additional 5 patients (10%) and 12 household members (24%) were colonized with methicillin-susceptible Staphylococcus aureus. Most MRSA isolates (95%; infective and colonizing) carried the staphylococcal cassette chromosome mec type IV complex, and 67% represented a single clone, identical to USA 300. Of the colonized household members, 5 had isolates related to the patients' infective isolate.
The frequency of CA-MRSA colonization among household members of patients with CA-MRSA infections is higher than rates reported among the general population. Among colonized household members, only half of the MRSA strains were related to the patients' infective isolate. Within the same household, multiple strains of CA-MRSA may be present.
Staphylococcus aureus is a common cause of infection, particularly in persons colonized by this organism. Virulent strains of methicillin-resistant S. aureus (MRSA) have emerged in the general community.
A nationally representative survey of nasal colonization with S. aureus was conducted from 2001 through 2004 as part of the National Health and Nutrition Examination Survey. MRSA isolates were identified by the oxacillin disk-diffusion method. The pulsed-field gel electrophoresis (PFGE) type was determined for all MRSA isolates. A t statistic was used to compare the prevalence of colonization across biennia and across population subgroups. Cofactors independently associated with colonization were determined with backward stepwise logistic modeling.
The prevalence of colonization with S. aureus decreased from 32.4% in 2001-2002 to 28.6% in 2003-2004 (P < .01), whereas the prevalence of colonization with MRSA increased from 0.8% to 1.5% (P < .05). Colonization with MRSA was independently associated with healthcare exposure in males and with having been born in the United States, age > or =60 years, diabetes, and poverty in females. In 2003-2004, a total of 19.7% (95% confidence interval, 12.4%-28.8%) of MRSA-colonized persons carried a PFGE type associated with community transmission.
Nasal colonization with MRSA has increased in the United States, despite an overall decrease in nasal colonization with S. aureus. PFGE types associated with community transmission only partially account for the increase in MRSA colonization.
As a result of waning immunity and improved awareness, the reported incidence of pertussis is increasing among adolescents in the United States. Symptoms of pertussis are often mild and difficult to diagnose in adolescents, but these individuals can transmit the infection to schoolmates and family members, including high risk infants. Improvements in diagnosis and prevention of pertussis in adolescents are needed.
The consequences of infection with Staphylococcus aureus can be severe, so strategies for prevention are important. We examined S. aureus isolates from blood and from nasal specimens to determine whether the organisms in the bloodstream originated from the patient's own flora.
In a multicenter study, swabs for culture were obtained from the anterior nares of 219 patients with S. aureus bacteremia. A total of 723 isolates were collected and genotyped. In a second study, 1640 S. aureus isolates from nasal swabs were collected over a period of five years and then compared with isolates from the blood of patients who subsequently had S. aureus bacteremia.
In the multicenter study of S. aureus bacteremia, the blood isolates were identical to those from the anterior nares in 180 of 219 patients (82.2 percent). In the second study, 14 of 1278 patients who had nasal colonization with S. aureus subsequently had S. aureus bacteremia. In 12 of these 14 patients (86 percent), the isolates obtained from the nares were clonally identical to the isolates obtained from blood 1 day to 14 months later.
A substantial proportion of cases of S. aureus bacteremia appear to be of endogenous origin since they originate from colonies in the nasal mucosa. These results provide support for strategies to prevent systemic S. aureus infections by eliminating nasal carriage of S. aureus.
Studies evaluating the risk of methicillin-resistant Staphylococcus aureus (MRSA)–associated sequelae in colonized or infected inpatients have not extended follow-up into the period after discharge
from the hospital. We determined the 18-month risk of MRSA infection among 209 adult patients newly identified as harboring
MRSA. Twenty-nine percent of patients (60 patients) developed subsequent MRSA infections (90 infections). These infections
were often severe. Twenty-eight percent of infections (25 of 90) involved bacteremia, and 56% (50 of 90) involved pneumonia,
soft tissue infection, osteomyelitis, or septic arthritis. Eighty percent of patients (48 of 60) with subsequent MRSA infection
developed the infection at a new site, and 49% of new MRSA infections (44 of 90) first became manifest after discharge from
the hospital. Accurate assessment of the risk of MRSA-associated sequelae requires prolonged follow-up after discharge.
We sought to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) among emergency department (ED) patients with skin and soft tissue infections, identify demographic and clinical variables associated with MRSA, and characterize MRSA by antimicrobial susceptibility and genotype.
This was a prospective observational study involving a convenience sample of patients who presented with skin and soft tissue infections to a single urban public hospital ED in California. Nares and infection site cultures were obtained. A health and lifestyle questionnaire was administered, and predictor variables independently associated with MRSA were determined by multivariate logistic regression. All S aureus isolates underwent antibiotic susceptibility testing. Eighty-five MRSA isolates underwent genotyping by pulsed field gel electrophoresis, staphylococcal chromosomal cassette mec (SCC mec ) typing, and testing for Panton-Valentine leukocidin genes.
Of 137 subjects, 18% were homeless, 28% injected illicit drugs, 63% presented with a deep or superficial abscess, and 26% required admission for the infection. MRSA was present in 51% of infection site cultures. Of 119 S aureus isolates (from infection site and nares), 89 (75%) were MRSA. Antimicrobial susceptibility among MRSA isolates was trimethoprim/sulfamethoxazole 100%, clindamycin 94%, tetracycline 86%, and levofloxacin 57%. Among predictor variables independently associated with MRSA infection, the strongest was infection type being furuncle (odds ratio 28.6). Seventy-six percent of MRSA cases fit the clinical definition of community associated. Ninety-nine percent of MRSA isolates possessed the SCC mec IV allele (typical of community-associated MRSA), 94.1% possessed Panton-Valentine leukocidin genes, and 87.1% belonged to a single clonal group (ST8:S).
In this urban ED population, MRSA is a major pathogen in skin and soft tissue infections. Although studies from other practice settings are needed, MRSA should be considered when empiric antibiotic therapy is selected for such infections.
Despite decades of high vaccination coverage, pertussis has remained endemic and reemerged as a public health problem in many countries in the past 2 decades. Waning of vaccine-induced immunity has been cited as one of the reasons for the observed epidemiologic trend. A review of the published data on duration of immunity reveals estimates that infection-acquired immunity against pertussis disease wanes after 4-20 years and protective immunity after vaccination wanes after 4-12 years. Further research into the rate of waning of vaccine-acquired immunity will help determine the optimal timing and frequency of booster immunizations and their role in pertussis control.
As a result of waning immunity and improved awareness, the reported incidence of pertussis is increasing among adolescents in the United States. Symptoms of pertussis are often mild and difficult to diagnose in adolescents, but these individuals can transmit the infection to schoolmates and family members, including high risk infants. Improvements in diagnosis and prevention of pertussis in adolescents are needed.
Since the 1980s, the occurrence of pertussis cases in developed countries has increased and shifted towards older age groups. This resurgence follows 30 years of intense mass vaccination, and has been attributed primarily to three factors: (1) more effective diagnosis of the disease, (2) waning of vaccine-induced immunity, and (3) loss of vaccine efficacy due to the emergence of new Bordetella pertussis strains. Here we develop and analyse a mathematical model to assess the plausibility of these hypotheses. We consider that exposure to B pertussis through natural infection or vaccination induces an immune response that prevents severe disease but does not fully prevent mild infections. We also assume that these protective effects are temporary due to waning of immunity. These assumptions, describing the mode of action of adaptive immunity, are combined with a standard transmission model. Two distinct epidemiological scenarios are detected: under low transmission, most infections lead to severe disease; under high transmission, mild infections are frequent, boosting clinical immunity and maintaining low levels of severe disease. The two behaviours are separated by a reinfection threshold in transmission. As a result, the highest incidence of severe disease is expected to occur at intermediate transmission intensities--near the reinfection threshold--suggesting that pertussis resurgence may be induced by a reduction in transmission, independently of vaccination. The model is extended to interpret the outcomes of current control measures and explore scenarios for future interventions.
A nasal swab specimen was collected for culture within 48 hours of admission and a questionnaire was completed using a convenience sample of 350 patients admitted to Driscoll Children's Hospital between February 15 and March 15, 2005. Of the 350 patients enrolled, 125 (36%) patients were colonized with Staphylococcus. aureus and 76 (61%) of the 125 S. aureus isolates were methicillin-resistant.
A 37-year-old man presents for the evaluation of localized swelling and tenderness of the left leg just below the knee. He suspects this lesion developed after a spider bite, although he did not see a spider. Examination of the leg reveals an area of erythema and warmth measuring approximately 5 by 7 cm. At the center of the lesion is a fluctu- ant area measuring approximately 2 by 2 cm, overlaid by a small area of necrotic skin. The man's temperature is 38.3°C. The pulse rate is 115 beats per minute. The blood pressure is 116/78 mm Hg. How should this patient be evaluated and treated?