Pertussis Vaccines

s of references provided in the position paper and GRADE tables  Amirthalingam G, Andrews N, Campbell H, Ribeiro S, Kara E, Donegan K, et al. Effectiveness of maternal pertussis vaccination in England: an observational study. Lancet 2014 Oct 25; 384(9953):1521-1528. BACKGROUND: In October, 2012, a pertussis vaccination programme for pregnant women was introduced in response to an outbreak across England. We aimed to assess the vaccine effectiveness and the overall effect of the vaccine programme in preventing pertussis in infants. METHODS: We undertook an analysis of laboratory-confirmed cases and hospital admissions for pertussis in infants between Jan 1, 2008, and Sept 30, 2013, using data submitted to Public Health England as part of its enhanced surveillance of pertussis in England, to investigate the effect of the vaccination programme. We calculated vaccine effectiveness by comparing vaccination status for mothers in confirmed cases with estimates of vaccine coverage for the national population of pregnant women, based on data from the Clinical Practice Research Datalink. FINDINGS: The monthly total of confirmed cases peaked in October, 2012 (1565 cases), and subsequently fell across all age groups. For the first 9 months of 2013 compared with the same period in 2012, the greatest proportionate fall in confirmed cases (328 cases in 2012 vs 72 cases in 2013, -78%, 95% CI -72 to -83) and in hospitalisation admissions (440 admissions in 2012 vs 140 admissions in 2013, -68%, -61 to -74) occurred in infants younger than 3 months, although the incidence remained highest in this age group. Infants younger than 3 months were also the only age group in which there were fewer cases in 2013 than in 2011 (118 cases in 2011 vs 72 cases in 2013), before the resurgence. 26?684 women included in the Clinical Practice Research Datalink had a livebirth between Oct 1, 2012 and Sept 3, 2013; the average vaccine coverage before delivery based on this cohort was 64%. Vaccine effectiveness based on 82 confirmed cases in infants born from Oct 1, 2012, and younger than 3 months at onset was 91% (95% CI 84 to 95). Vaccine effectiveness was 90% (95% CI 82 to 95) when the analysis was restricted to cases in children younger than 2 months. INTERPRETATION: Our assessment of the programme of pertussis vaccination in pregnancy in England is consistent with high vaccine effectiveness. This effectiveness probably results from protection of infants by both passive antibodies and reduced maternal exposure, and will provide valuable information to international policy makers. FUNDING: Public Health England.  Bar-ON ES, Goldberg E, Hellmann S, Leibovici L. Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB). Cochrane Database for Systematic Reviews 2012;(4):CD005530. BACKGROUND: Advantages to combining childhood vaccines include reducing the number of visits, injections and patient discomfort, increasing compliance and optimising prevention. The World Health Organization (WHO) recommends that routine infant immunisation programmes include a vaccination against Haemophilus influenzae (H. influenzae) type B (HIB) in the combined diphtheria-tetanus-pertussis (DTP)-hepatitis B virus (HBV) vaccination. The effectiveness and safety of the combined vaccine should be carefully and systematically assessed to ensure its acceptability by the community. OBJECTIVES: To compare the effectiveness of combined DTP-HBV-HIB vaccines versus combined DTP-HBV and separate HIB vaccinations. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1966 to week 1, November 2011), EMBASE (January 1990 to November 2011) and www.clinicaltrials.gov (up to April 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing vaccination with any combined DTP-HBV-HIB vaccine, with or without three types of inactivated polio virus (IPV) or concomitant oral polio vaccine (OPV) in any dose, preparation or time schedule, compared with separate vaccines or placebo, administered to infants up to two years old. DATA COLLECTION AND ANALYSIS: Two review authors independently inspected references identified by the searches and evaluated them against the inclusion criteria, extracted data and assessed the methodological quality of included trials. MAIN RESULTS: Data for the primary outcome (prevention of disease) were lacking. We performed a meta-analysis to pool the results of 20 studies with 5874 participants in an immunogenicity analysis and 5232 participants in the reactogenicity analysis. There were no data on clinical outcomes for the primary outcome (prevention of disease) and all studies used immunogenicity and reactogenicity (adverse events). The number of vaccine doses differed significantly between the studies. Heterogeneous interventions, study location, healthcare environment and combining research across disparate geographical locations, may have lead to bias. The risk of bias was unclear across most of the included studies. Comparisons found little heterogeneity. In two immunological responses the combined vaccine achieved lower responses than the separate vaccines for HIB and tetanus. No significant differences in immunogenicity were found for pertussis, diphtheria, polio and hepatitis B. Serious adverse events were comparable with mainly hospitalisation and acute bronchiolitis cases. Minor adverse events such as pain and redness were more common in children given the combined vaccine. Overall, the direction shown by the results is in favour of the DTPw (diptheria-tetanus-whole cell pertussis)-HBV-HIB vaccine rather than the DTPa (diptheria-tetanus-acellular pertussis)-HBV-HIB vaccine when compared to the separate vaccines (size of effect: risk ratio (RR) 1.43; 95% confidence interval (CI) 0.98 to 2.10, for 5269 participants). AUTHORS' CONCLUSIONS: We could not conclude that the immune responses elicited by the combined vaccine were different from or equivalent to the separate vaccines. There was significantly less immunological response for HIB and tetanus and more local reactions in the combined injections. However, these differences rely mostly on one study each. Studies did not use an intention-to-treat (ITT) analysis and we were uncertain about the risk of bias in many of the studies. These results are therefore inconclusive. Studies addressing clinical end points whenever possible, using correct methodology and a large enough sample size should be conducted.  Beutels P, Bonanni P, Tormans G, Canale F, Crovari PC. An economic evaluation of universal pertussis vaccination in Italy. Vaccine 1999 May 14;17(19):2400-2409. An economic evaluation was performed of universal acellular pertussis vaccination in Italy, where until recently the overall coverage of pertussis vaccination was estimated at 50%. Over the last two years coverage seems to have increased rapidly. By means of a mathematical simulation model, the consequences of pertussis vaccination in terms of both health effects and economic costs were calculated for a single birth cohort followed for 6 years. Incremental analyses were performed for each additional 10% increase in coverage from 50-90%. The results indicate that a 50% coverage rate of pertussis vaccination in Italy was not optimal on the basis of cost-effectiveness and cost-benefit considerations. Additional increases in coverage were found to yield extra health gains at modest net costs or even potential net savings to the health care sector. For example, an increase in coverage to 90% would yield direct net savings of US$42 per extra vaccinee in comparison to a situation of 50% coverage. The total net savings for this strategy would be well over US$100 per additional vaccinee. In the sensitivity analysis, the positive relationship between incremental coverage and incremental efficiency remained unchanged.  Bisgard KM, Rhodes P, Connelly BL, Bi D, Hahn C, Patrick S, et al. Pertussis vaccine effectiveness among children 6 to 59 months of age in the United States, 1998-2001. Pediatrics 2005;116. BACKGROUND: Despite the dramatic pertussis decrease since the licensure of whole-cell pertussis (diphtheria-tetanus toxoids-pertussis [DTP]) vaccines in the middle 1940s, pertussis remains endemic in the United States and can cause illness among persons at any age; >11000 pertussis cases were reported in 2003. Since July 1996, in addition to 2 DTP vaccines already in use, 5 acellular pertussis (diphtheria-tetanus toxoids-acellular pertussis [DTaP]) vaccines were licensed for use among infants; 3 DTaP vaccines were distributed widely during the study period. Because of the availability of 3 DTaP and 2 DTP vaccines and the likelihood of the vaccines being used interchangeably to vaccinate children with the recommended 5-dose schedule, measuring the effectiveness of the pertussis vaccines was a high priority. OBJECTIVE: To measure the pertussis vaccine effectiveness (VE) among US children 6 to 59 months of age. DESIGN: We conducted a case-control study in the Cincinnati, Ohio, metropolitan area, Colorado, Idaho, and Minnesota. PARTICIPANTS: Confirmed pertussis cases among children 6 to 59 months of age at the time of disease onset, with onset in 1998-2001, were included. For each case subject, 5 control children were matched from birth certificate records, according to the date of birth and residence. OUTCOME MEASURES: A standardized questionnaire was used to obtain vaccination data from parents and providers. Parents/guardians were asked about demographic characteristics, child care attendance, the number of household members who stayed at the same home as the enrolled child for > or =2 nights per week, and cough illness of > or =2-week duration among these household members in the month before the case patient's cough onset. Pertussis vaccine doses among case children were counted as valid if they were received > or =14 days before the cough onset date ("valid period"). The age of the case patient (in days) at the end of the valid period was determined, and doses of vaccine for the matched control subjects were counted as valid if they were received by that age. Conditional logistic regression models were used to estimate the matched odds ratios (ORs) for pertussis according to the number of pertussis vaccine doses. The VE was calculated with the following formula: (1 OR) x 100. Because the pertussis antigen components or amounts differed according to vaccine, the VE of 3 or 4 doses of DTP and/or DTaP was estimated according to the recorded vaccine manufacturer and vaccine type. RESULTS: All enrolled children (184 case subjects and 893 control subjects) had their vaccine history verified. The proportions of children who received 0, 1 or 2, 3, and > or =4 pertussis (DTP and/or DTaP) vaccine doses among case subjects were 26%, 14%, 26%, and 34% and among control subjects were 2%, 8%, 33%, and 57%, respectively. Compared with 0 doses, the unadjusted VE estimate for 1 or 2 pertussis doses was 83.6% (95% confidence interval [CI]: 61.1-93.1%), that for 3 doses was 95.6% (95% CI: 89.7-98.0%), and for > or =4 doses was 97.7% (95% CI: 94.7-99.0%). Among children who received 4 pertussis vaccinations, the risk of pertussis was slightly higher among those who received only 1 type of vaccine (either 4 DTP doses or 4 DTaP doses), compared with those who received a combination of DTP for doses 1 to 3 and DTaP for dose 4 (OR: 2.4; 95% CI: 1.1-5.2). Among children who received 3 or 4 DTaP vaccine doses, the risk of pertussis was slightly higher among those who received a DTaP vaccine with 4 pertussis antigen components (a vaccine no longer available), compared with those who received the DTaP vaccine with 2 pertussis antigen components (OR: 2.5; 95% CI: 1.1-5.8). Among children who received 4 doses, the risk of pertussis was 2.7 times higher for children who received dose 4 early (age of < or =13 months), compared with children who received dose 4 at an older age (age of > or =14 months) (95% CI: 1.1-6.8). For children 6 to 23 months of age, features of household structure were significant risk factors for pertussis. In a multivariate model, compared with living with an older parent (> or =25 years of age), not living with an "other" household member (a relative other than a parent or sibling or a nonrelated person), and not living with a sibling 6 to 11 years of age, the risk of pertussis for children 6 to 23 months of age was 6.8 times higher if they lived with a young parent (< or =24 years of age) (95% CI: 3.1-15.0), 2.5 times higher if they lived with an "other" household member (95% CI: 1.2-5.4), and 2.2 times higher if they lived with a sibling 6 to 11 years of age (95% CI: 1.2-4.3). Adjusting for these risk factors did not change the VE. Compared with control children, case children were significantly more likely to live with a household member (representing all age groups and relationships) who reported a recent cough illness with duration of > or =2 weeks (87 [52%] of 168 case subjects, compared with 79 [8%] of 860 control subjects). CONCLUSIONS: Any combination of > or =3 DTP/DTaP vaccine doses for children 6 to 59 months of age was highly protective against pertussis. However, there were differences according to vaccine type (DTaP or DTP) and DTaP manufacturer. Among children who received 4 pertussis vaccine doses, a combination of 3 DTP doses followed by 1 DTaP dose had a slightly higher VE than other combinations; among children who received 3 or 4 DTaP vaccine doses, 1 DTaP vaccine performed less well. The finding that pertussis dose 4 was more effective when given to children at > or =14 months of age might be confounded if health care providers were more likely to vaccinate children at 12 months of age because of a perceived risk of undervaccination and if these same children were also at higher risk for pertussis. Household members of any age group and relationship could have been the source of pertussis, and household structure was associated with risk for pertussis for children 6 to 23 months of age. In contrast to control children in the study, 26% of case children had never been vaccinated against pertussis. Unvaccinated children are at risk for pertussis and, in a community with other unvaccinated children, can lead to community-wide pertussis outbreaks. Parents need to be educated about the morbidity and mortality risks associated with Bordetella pertussis infection, and they need to be encouraged to vaccinate their children against pertussis on time and with the recommended number of vaccine doses for optimal protection.  Brenzel L, Wolfson LJ, Fox-Rushby J, Miller M, Halsey NA. Vaccine preventable diseases. In: Jamison DT, Breman JG, Measham AR et al. eds. Disease control priorities in developing countries. 2nd ed. New York, Oxford University Press, 2006:389-412. Available at http://www.ncbi.nlm.nih.gov/books/NBK11728/ (Accessed August 2015). DCP2 is a comprehensive, 1440-page resource that provides an updated "checkup" for global health and health care. As part of the "health examination," DCP2 asked: What progress has been made in defining and reducing the global burden of disease? How much have countries accomplished in developing and providing efficient, effective, and equitable health care? How can they set and achieve priorities in health services? Once these countries have identified the priorities, how can they deliver interventions to the targeted population in the most costeffective manner? How can the efforts of the health and closely related sectors (such as nutrition, agriculture, water and sanitation, and education) be integrated to optimize health improvements? DCP2's answers contribute substantially to global initiatives to improve the health of all peoples by providing a multidisciplinary understanding of these fundamental issues and challenges, as well as effective interventions for the range of communicable and noncommunicable diseases and conditions and risk factors. Underlying all medical and economic analyses is the appreciation of the need to strengthen health systems so that they can provide highly cost-effective interventions on a large scale. Applying the information, analysis, and strategies set out in DCP2 requires a careful assessment of the local situation, including patterns of disease, institutional capacity, and resources. Combining insights from DCP2 and knowledge of their local situation, actors at many levels— from parliamentarians and health ministers to hospital administrators, health care workers, and concerned citizens—will be able to set priorities, select appropriate interventions, devise better means of delivery, improve management, and be more effective in mobilizing resources. In this manner, the benefits of technical progress in improving health can be extended and shared by all.  Briand V, Bonmarin I, Levy-Bruhl D. Study of the risk factors for severe childhood pertussis based on hospital surveillance data. Vaccine 2007 Oct 10;25(41):7224-7232. We used data collected through the French national hospital-based pertussis surveillance network to investigate the risk factors for severe childhood pertussis and more specifically the impact of the vaccination status. For infants, factors associated with a decreased risk of severe disease (defined as hospitalization in intensive care unit, assisted ventilation or death) were having received the first dose of vaccine, being seen late in the course of the disease and in a local hospital. Data also suggested that protection may increase with the number of doses administered. For older children, factors associated with a decreased risk of severity, measured by the hospitalization, were having received a recent booster injection and identification of the contaminator in the close environment. This study reinforces the need for an early start of the primary course in infants and the administration of booster injections in older children.  Brown NJ, Berkovic SF, Scheffer IE. Vaccination, seizures and 'vaccine damage'. Curr Opin Neurol 2007 April;20(2):181-187. PURPOSE OF REVIEW: Concerns about the safety of vaccination have plagued the community, with reduction in vaccine uptake resulting in increased risk of epidemics. Vaccination has been implicated in the cause of febrile seizures, 'vaccine encephalopathy' and autistic spectrum disorders. Evaluation of alleged associations is complicated by evolution in the vaccination field. This review focuses on the risk of seizures following vaccination and the alleged associations of vaccination with vaccine encephalopathy and also with autism spectrum disorders. RECENT FINDINGS: Over the last decade the introduction of new vaccines such as the acellular pertussis vaccine has produced a reduction in seizures following vaccination, the outcome of which was benign even with older vaccines. New evidence emerged in 2006 showing that cases of alleged 'vaccine encephalopathy' are due to mutations within a sodium channel gene. The weight of epidemiological evidence does not support a relationship between vaccination and childhood epileptic encephalopathies or autism spectrum disorders. SUMMARY: Vaccines are safer than ever before, but the challenge remains to convey this message to society in such a way that produces change in attitudes to vaccination and subsequent increase in vaccine coverage.  Bryant KA, Humbaugh K, Brothers K, Wright JBSN, Pascual FB, Moran J, et al. Measures to Control an Outbreak of Pertussis in a Neonatal Intermediate Care Nursery After Exposure to a Healthcare Worker. Infection Control & Hospital Epidemiology 2006 June;27(6):541-545. BACKGROUND: Hospitalized premature infants are particularly vulnerable to morbidity and mortality from pertussis. Effective prevention and investigative and control measures are not well described. OBJECTIVE: To identify the source of nosocomial pertussis in a 2-month-old premature infant in a neonatal intermediate care nursery (ICN) and to critically review the investigation and outbreak control measures. SETTING: An ICN and a neonatal intensive care unit. METHODS: We queried healthcare workers (HCWs) and family members about cough illness and contacted potentially exposed patients to determine whether they had symptoms of pertussis. Culture and polymerase chain reaction (PCR) testing for Bordetella pertussis were performed by the hospital laboratory with specimens collected from symptomatic patients and HCWs. Levels of pertussis toxin immunoglobulin G antibodies were measured in HCWs with cough of at least 14 days' duration at a public health laboratory. Extensive control measures were instituted. RESULTS: Four ICN HCWs met the clinical case definition for presence of pertussis. Serologic test results were positive for 3 of the HCWs. The primary case patient was a 36-year-old HCW with a cough illness of 3-weeks' duration that was accompanied by paroxysms, whoop, posttussive emesis, and pneumothorax. Among the 4 affected HCWs, the duration of cough illness prior to identification of the infant index patient ranged from 11 to 25 days. Outbreak control measures included isolation of the infant case patient, furlough and treatment of symptomatic HCWs, administration of chemoprophylaxis to contacts, and surveillance for additional cases. Seventy-two infant patients and 72 HCWs were exposed and were given antibiotic prophylaxis. One additional case of pertussis, confirmed by PCR and culture, occurred in a resident physician who declined prophylaxis; she had cared for the index patient but had no contact with symptomatic HCWs. CONCLUSION: HCWs or patients may serve as the source of pertussis in nosocomial outbreaks, which can result in substantial morbidity and outlay of resources for control measures. Our review suggested that a diagnosis of pertussis should be an early consideration for HCWs with cough illness. Targeted pertussis immunization of HCWs, employee health policies that provide for testing and furlough of HCWs with prolonged cough, and monitoring of HCWs for compliance with infection control measures could reduce the morbidity and costs associated with pertussis outbreaks. These measures will require evaluation of their effectiveness.  Campbell H, Amirthalingam G, Andrews N, Fry NK, George RC, Harrison TG, et al. Accelerating control of pertussis in England and Wales. Emerg Infect Dis 2012 Jan;18(1):38-47. Results of an accelerated pertussis vaccination schedule for infants introduced in 1990 in England and Wales were examined. Earlier scheduling and sustained high vaccine coverage resulted in fewer reported cases of pertussis among infants, reinforcing the World Health Organization drive for on-time completion of the infant vaccination schedule. As determined by using the screening method, the first dose of vaccine was 61.7% effective in infants <6 months of age, and effectiveness increased with subsequent doses. Three doses of a good whole-cell pertussis vaccine were 83.7% effective in children 10–16 years of age; a preschool booster vaccination further reduced pertussis incidence in children <10 years of age. As in other industrialized countries, surveillance data during 1998–2009 showed that pertussis in England and Wales mainly persists in young infants (i.e., <3 months of age), teenagers, and adults. Future vaccine program changes may be beneficial, but additional detail is required to inform such