Whooping cough causes significant morbidity and mortality, especially in early infancy. Although an effective vaccine exists, vaccine uptake in Malta was previously disappointing due to the general public’s and the medical community’s doubts regarding vaccine efficacy and safety. The aim of this study was to review population-based studies which have analysed the potential short and long term neurological sequelae following pertussis and pertussis vaccination, to describe vaccine uptake globally and in Malta over the past 15 years, and to analyse the effect of vaccine uptake on pertussis epidemics in Malta. This study found that pertussis vaccine uptake has only become satisfactory in recent years, with a resulting attenuation in the most recent pertussis outbreak. Uptake has increased progressively all over the world, and no study has ever incriminated pertussis vaccination as a cause of permanent neurological disability, both locally and abroad. This should encourage the present continuing trend of pertussis uptake.peer-reviewe

Busuttil, Ray

Grech, Victor E.

English

OAR@UM

Maltese Medical Journal, 1998; 10(1):15 15 All rights reserved Brain damage following whooping cough vaccination ~ - is it time to lay the myth to rest? Victor E Grech*, Ray Busuttil** 1 ABSTRACT: Whooping cough causes significant morbidity and mortality, especially in early infancy. Although an effective vaccine exists, vaccine uptake in Malta was previously disappointing due to the general public's and the medical community's doubts regarding vaccine efficacy and safety. The aim of this study was to review population-based studies which have analysed the potential short and long term neurological sequelae following pertussis and pertussis vaccination, to describe vaccine uptake globally and in Malta over the past 15 years, and to analyse the effect of vaccine uptake on pertussis epidemics in Malta. This study found that pertussis vaccine uptake has only become satisfactory in recent years, with a resulting attenuation in the most recent pertussis outbreak. Uptake has increased progressively all over the world, and no study has ever incriminated pertussis vaccination as a cause of permanent neurological disability, both locally and abroad. This should encourage the present continuing trend of pertussis uptake. * Department of Paediatrics, St Lukes Hospital, Gwardamangia, Malta. ** Department of Primary Health Care, F1oriana, Malta. Correspondence: Dr. VE Grech, Department of Paediatrics, SI. Luke's Hospital, Guardamangia, Malta. email: vgrech@mail.link.net.mt Work Should Be Attributed To : Paediatric Department, St. Luke's Hospital, Guardamangia and Department of Primary Health Care, Floriana . Keywords: whooping cough, encephalopathy, vaccination Introduction Methods Whooping cough is a bacterial infection caused by Medline was searched using the keywords 'whooping Bordatella pertussis, which can cause significant cough' and 'encephalopathy'. Population-based studies morbidity and mortality . Infants between 1 and 2 months which analysed cases of encephalopathy occurring in of age are at highest risk for pertussis, along with the association with pertussis or pertussis vaccination were highest rates of hospitalisation (82%), pneumonia (25%), identified. For the estimation of pertussis vaccine uptake, seizures (2-4%), encephalopathy (0.3-1%), and death since the pertussis vaccine is almost invariably given as (0.2-1 %)1,2. a combined DTP vaccine, the statistics for the combined Neurological symptoms may be caused by endotoxin vaccine were used. Pertussis vaccine uptake was defined release due to bacterial lysis, asphyxia, CO2 retention, as percentage of infants surviving the first year of life, loss of cerebral vascular autoregulation, or a who have received three doses of combined vaccine combination of these factors2. Seizures, encephalopathy (DTP3). Unless stated otherwise, DTPIDTP3 refer to the and other neurological manifestations are complications whole-cell pertussis vaccine, which does not include that also occur in adults3. vaccination with acellular preparations of pertussis A widespread impression that Diphtheria-Tetanus­ vaccine. Pertussis (DTP) vaccine can cause brain damage was DTP3 data for Malta was obtained from statIstIcs initially based on historical precedent. Smallpox and maintained by the Department of Primary Health Care, rabies vaccines were recognised as occasionally causing while DTP3 statistics for individual countries - such as devastating neurological complications, and in the minds the United Kingdom - and for global regions, were of the lay public and the medical community, this obtained from WorId Health Organisation analogy was extended to pertussis. In addition, anecdotal publications5,6 . case reports of a syndrome of pertussis vaccine Annual Maltese figures for w(lOoping cough were encephalopathy began to be reported over 60 years obtained from 1980 to 19965. Annual population ag04.This study reviews the literature regarding pertussis estimates? were then used to calculate Maltese pertussis and pertussis vaccine related complications, with rates per 100,000 population. emphasis on neurological complications, reviews the Excel was used for data entry and for charting. SPSS literature regarding pertussis vaccine uptake, and was used for non-parametric correlations of vaccine compares this with the situation in Malta. uptake and pertussis rates with time (Kendall's t test). A p value of 0.05 was taken to represent a statistically significant result. 16 V. E. Grech, R. Busuttil Table 1 - Correlation of percentage uptake of 3 doses of combined diphtheria, tetanus, pertussis and polio vaccine by 1 year of age with time -Results Globally DTP3 uptake has increased significantly in all of the World Health Organisation regions (p:5 0.001 - Table 1). WHO global statistics show DTP3 uptake has more than doubled in the past 15 years, from approximately 35% to almost 80% (Figure 1). Analysis of DTP3 for developed regions shows >80% uptake for the UK and America (Figure 1). Although uptake is not as high indeveloping regions, the trend is persistently upwards (Figure 2). Locally DTP3 uptake in Malta has increased significantly (Table 1), climbing rapidly since the mid-1990s to reach the 80% level (Figure 3). Pertussis outbreaks in Malta show classical 4-yearly peaks (Figure 3). The last classical outbreak was in 1991, and the effect of DTP3>40% is instantly discernible, with attenuation of the next expected outbreak in 1995. There have been no cases of permanent neurological sequelae definitively attributable to DTP vaccination. Discussion Historical background to DTP vaccination The development and extensive uptake of an effective DTP vaccine (taken in three doses in infancy) in the United States in the 1930s led to a decline in the incidence of pertussis in this region, and instilled confidence in a vaccination programme which continues to this day. This contrasts with the turbulent history of pertussis vaccination in the United Kingdom, where doubts as to the efficacy of pertussis vaccines delayed their active national promotion until the late 1950s, after which various reports reinforced the . medical community's and the general public's doubts regarding DTP vaccine efficacy and safety4. In 1974, the media were deeply embroiled in the issue when the National Hospital for Sick Children case series of neurological events was aired in a television documentary. This study allegedly identified patients with neurological sequelae which had occurred after DTP vaccination. The Courts were also involved when a claim for damages in the High Court of Justice in London in 1989 (Loveday vs Renton and The Wellcome Foundation) dealt with the issue of whether pertussis vaccine could cause permanent neurological sequelae. The foundation of this claim was the apparent clustering of neurological disorders within the fIrst 24 to 48 hours after DTP vaccination. One of the findings of the National Childhood Encephalopathy Study (NCES) which came to light in court, was that permanent brain damage did not occur within 48 hours of DTP vaccination in any child in England, Scotland and Wales from mid-1976 to mid-1979, when two million doses of vaccine had been given, although an excess of febrile convulsions in the first 24 hours was noted. All temporally associated cases with permanent sequelae had either viral encephalitis or Reye's syndrome, and no cases were unexplained8. The High Court's judgement was that there was no evidence that DTP vaccination causes permanent neurological sequelaeB• A reduction of DTP uptake, or even discontinuation, Malta UK WHO regions Europe America E. Mediterranean Africa S.E. Asia W. Pacific Global Year 1984-96 1981-94 1980-96 1980-96 1980-96 1980-96 1980-96 1980-96 1980-96 t 0.87 1 0.75 0.88 0.82 0.71 0.67 0.63 0.86 P <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.001 <0.0001 Fig. 1 - Percentage uptake of 3 doses of combined diphtheria, tetanus, pertussis and polio vaccine by 1 year of age in WHO developed regions (UK and America), the UK and globally 100 90 80 Percenuge 70 uptake of 60 3 doses of SODTPwccine by 1 year ----+-- AmHica40 o(age 30 --....-Europe 20 _..•. __ Global 10 I o 1 1980 1982 1984 1986 1988 1990 1992 1994 1996 Birth cohort Fig. 2 - Percentage uptake of 3 doses of combined diphtheria, tetanus, pertussis and polio vaccine by 1 year of age in WHO developing regions I --- £.~"di",,.n<an~A7'ica ___ S.£.. ..uia __ W. Pacinc 100 90 80 Percentage 70 uptake of 60 3 doses of SODTP vaccine by) yur 40 of age 30 20 10 0 1980 1982 1984 1986 )988 1990 1992 1994 1996 Birtb cohort Fig. 3 - Percentage uptake of 3 doses of combined diphtheria, tetanus, pertussis and polio vaccine Percen13ee uj:t2ke of J doses or DTP l1II('cine by I yur o(.ge by 1 year of age in Malta and pertussis rates [.~~----------- -;1 . . .• _. OTP) --+-- Pertussis/ IOO.OOO population I ------- -.- ----- - ----- - --.­100 90 80 Pertussis 40 rate per 100.000 30 ,.UI p>pJlarioD20 10il 161'\·1\·~ SO 1980 1985 1990 1995 Birth cohort for OTP) and year for ::annu21 pertussis nits 17 Brain damage following whooping cough vaccination -was also observed in other countries, including Sweden. Japan, the USSR, Ireland, Italy, the former West Germany and Australia, leading to a sharp rise in the number of reported cases of pertussis during epidemics9• On the other hand, countries which maintained a high or compulsory uptake of DTP, including Hungary, the former East Germany, Poland and the United States, had reported rates of pertussis which were 10-100 times lower9. In the United Kingdom, confidence in DTP was enhanced by introducing the vaccine at an earlier age, which is associated with a decreased incidence of reactions. This practice was also followed in Malta. Known complications ofDTP vaccination DTP vaccination may cause various reactions within 48 hours of administration, which include hypotonic­hyporesponsive episodes, seizures and fever ~ 40.5°CiO. Children with seizures tend to have a high rate of personal and family histories of seizures, and fever occurring in association with DTP vaccination (~ 380C)10. Persistent crying (~ 3 hours) is generally noted in association with painful local reactions~o. A rare association has also been described between DTP vaccination and anaphylaxis 11. Large, population-based studies have concluded that combined DTP vaccine may, on rare occasions be associated with the development of severe acute neurological illnesses, with only the potential for severe, long-term sequelae. Some of the cases of severe acute neurological illnesses observed may have occurred due to chance alone, or may have had other causes. It is impossible to determine retrospectively the role of the pertussis component of the vaccine in these case.s, as a primary or secondary factor I2-15 . It is important to emphasise that no population studies have ever implicated DTP vaccination as a cause of permanent neurological sequelae, and this must be weighed against the known morbidity and mortality that occurs in assoclatlOn with pertussis itself. DTP vaccination is given at the age of emergence of primary neurologic disease, and a temporal link between DTP vaccination and the recognition of such problems may be established in the minds of parents and doctors alike, and a causal link inferred. Also, no evidence has been found to link DTP vaccination with infantile spasms, hypsarrhythmia, Reye's syndrome, aseptic meningitis, Guillain-Barre syndrome, peripheral mononeuropathy, or indeed, any form of chronic neurologic damage including learning disabilities and attention-deficit disorder I I. Furthermore. no link has been found with sudden infant death syndrome, erythema multiforme or other rashes. haemolytic anaemia, juvenile diabetes, or thrombocytopenia11. The following are the modem contraindications to pertussis vaccination 16: Severe local reactions: • More than half the limb involved. Severe generalised reactions: • Marked febrile reactions (> 39.5 0C) within 48 hours of vaccination • Allergic reactions: Anaphylaxis, bronchospasm or laryngeal oedema • Generalised collapse • Prolonged unresponsiveness • Prolonged screaming (> 4 hours) • Convulsions or encephalopathy within 48 hours of vaccination Failure to vaccinate must be weighed against the known morbidity and mortality of pertussis itself. Vaccinators should be strongly discouraged from the inappropriate deferral of pertussis immunisation due to mild illness, or the omission of vaccine because of non­existent contraindications. This is especi'ally important in children who have underlying conditions which may place them at greater risk of acquiring pertussis infection and its potential complications. Locally Malta has followed the rest of the world in increasing the uptake of pertussis vaccination over the past decade. The effect of a high herd immunity limiting the spread of pertussis, which has been brought about by a high uptake of DTP3, is readily apparent (Figure 3), with a marked drop in the number of reported cases in the most recent pertussis outbreak, when compared to previous outbreaks. Increased uptake is attributed to a number of factors including the effective allaying of misguided public fears by the Department of Primary Health Care with regard to vaccine safety, and an increasing number of local paediatricians who follow logical guidelines in pertussis vaccination practice. A further stimulus to vaccination would also include morbidity and mortaIity observed locally 17. Conventional DTP consists of killed whole organisms (whole-cell vaccine). A new acellular pertussis vaccine, containing partially purified protein antigens, fIlamentous hemagglutinin, and lymphocytosis­promoting factor hemagglutinin has been developed for use, and was initially tested in Japan in a randomised double-blind trial, vaccinating children at the appropriate time. Acellular pertussis vaccine was found to be significantly less reactogenic for fever, pain, fretfulness and local reactions at the vaccine administration site 18 . The role of this vaccine is uncertain, and the World Health Organisation continues to recommend use of whole-cell vaccine. Conclusions Pertussis is a dangerous and potentially lethal illness, immunisation is effective in protecting against the disease, and should therefore be strongly encouraged. There is no proof that the incidence of complications from DTP whole-cell vaccination of children with seizure disorders or other pre-existing stable neurologic abnormalities is higher. and therefore the balance of possible risk against known benefits of pertussis immunisation supports continued use of the DTP vaccination even under such circumstances. There is overwhelming evidence to show that the occasional neurological illness following whole-cell DTP vaccination has a temporal, rather than a causal relationship. as the vaccine is given at the age of emergence or recognition of primary neurologic disease. -----V. E. Grech, R. Busuttil 18 References 1. 	 Farizo KM, Cochi SL, Zell ER, Brink EW, Wassilak SG, Pab'iarca P A. Epidemiological features of pertussis in the United States, 1980-1989. Clin Infect Dis 1992; 14: 708­719. 2. 	 Menkes rn, Kinsboume M. Workshop on neurologic complications of pertussis and pertussis vaccination. Neuropediatrics 1990; 21: 171-176. 3. 	 Halperin SA, Marrie n. Pertussis encephalopathy in an adult: case report and review. Rev Infect Dis 1991; 13: 1043-1047. 4. 	 Madsen T. Vaccination against whooping cough. JAMA 1933; 101: 187-188. - 5. 	 World Health Organisation. EPI information system summary for the WHO European region. WHO, Geneva: 1996. 6. 	 World Health Organisation. EPI information system global summary. WHO, Geneva: 1996. 7. 	 Central Office of Statistics. Demographic review for the Maltese Islands: Central Office of Statistics (annual publication). 8. 	 Miller DL, Ross EM, Alderslade R, Bellman MH, Rawson NS. Pertussis immunisation and serious acute neurological illness in children. Br Med J (Clin Res Ed) 1981; 282: 1595-1599. 9. 	 Gangarosa EJ, Galazka AM, Wolfe CR, Phillips LM, Gangarosa RE, Miller E, Chen RT. Impact of anti-vaccine movements on pertussis control: the untold story. Lancet 1998; 351: 356-361. 10. 	 Blumberg DA, Lewis K, Mink CM, Christenson PD, Chatfield P, Cherry ID. Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying. Pediatrics 1993; 91: 1158-1165. 11. 	 Howson CP, Fineberg HV. Adverse events following pertussis and rubella vaccines. Summary of a report of the Institute of Medicine. JAMA 1992; 267: 392-396. 12. 	 Miller D, Madge N, Diamond J, Wadsworth J, Ross E. Pertussis immunisation and serious acute neurological illnesses in children. BMJ 1993; 307: 1171-1176. 13. 	 Cowan LD, Griffin MR, Howson CP, Katz M, Johnston RB Jr, Shaywitz BA, Fineberg HV. Acute encephalopathy and chronic neurological damage after pertussis vaccine. Vaccine 1993; 11: 1371-1379. 14. 	 Incorpora G, Pavone L, Parano E, Cocuzza M, Catalano F, Trifiletti R. Neurological complications in hospitalized patients with pertussis: a 15-year Sicilian experience. Childs Nerv Syst 1996; 12: 332-335. 15. 	 Griffin MR, Ray WA, Mortimer EA, Fenichel GM, Schaffner W. Risk of seizures and encephalopathy after immunization with the diphtheria-tetanus-pertussis vaccine. JAMA 1990; 263: 1641-1645. 16. 	 Department of Health, Welsh Office, Scottish Office,DHSS (N. Ireland). Immunisation against infectious disease: HMSO,UK: 1996. 17. 	 Russell-Jones DL, Treacher DF, Lenicker HM, Tashanov M, Spencer GT. Central hypoventilation in a seven year old child following pertussis treated with negative pressure ventilation. Postgrad Med J 1989; 65: 768-770. 18. 	 Edwards KM, Lawrence E, Wright PF. Diphtheria, tetanus, and pertussis vaccine. A comparison of the immune response and adverse reactions to conventional and acellular pertussis components. Am J Dis Child 1986; 140: 867 -871. The copyright of this article belongs to the Editorial Board of the Malta Medical Journal. The Malta Medical Journal’s rights in respect of this work are as defined by the Copyright Act (Chapter 415) of the Laws of Malta or as modified by any successive legislation. Users may access this full-text article and can make use of the information contained in accordance with the Copyright Act provided that the author must be properly acknowledged.  Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. This article has been reproduced with the authorization of the editor of the Malta Medical Journal (Ref. No 000001)  

Acute encephalopathy and chronic neurological damage after pertussis vaccine. Vaccine

Adverse events following pertussis and rubella vaccines. Summary of a report of the Institute of Medicine. JAMA

Central hypoventilation in a seven year old child following pertussis treated with negative pressure ventilation. Postgrad Med J

Central Office of Statistics. Demographic review for the Maltese Islands: Central Office of Statistics (annual publication).

Epidemiological features of pertussis in the United States, 1980-1989. Clin Infect Dis

Immunisation against infectious disease: HMSO,UK:

Impact of anti-vaccine movements on pertussis control: the untold story. Lancet

Marrie n. Pertussis encephalopathy in an adult: case report and review. Rev Infect Dis

Neurological complications in hospitalized patients with pertussis: a 15-year Sicilian experience. Childs Nerv Syst

Organisation. EPI information system global summary.

Pertussis immunisation and serious acute neurological illness in children.

Pertussis immunisation and serious acute neurological illnesses in children. BMJ

Risk of seizures and encephalopathy after immunization with the diphtheria-tetanus-pertussis vaccine. JAMA

Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying. Pediatrics

Vaccination against whooping cough. JAMA 1933; 101: 187-188. - 5. World Health Organisation. EPI information system summary for the WHO European region.

Workshop on neurologic complications of pertussis and pertussis vaccination. Neuropediatrics

Brain damage following whooping cough vaccination : is it time to lay the myth to rest?

https://www.um.edu.mt/library/oar/bitstream/handle/123456789/593/mmj100115.pdf?sequence=1&isAllowed=y

Brain damage following whooping cough vaccination : is it time to lay the myth to rest?

Abstract

Similar works

Full text

Available Versions

OAR@UM