THE UNIVERSITY OF EDINBURGH

COURSE: GLOBAL HEALTH AND INFECTIOUS DISEASES

COURSE UNIT:UNDERSTANDING INFECTIOUS DISEASES EXAMINATION NUMBER; B031718

Written assignment 2. Potential health gain following the introduction of 3 dose acellular pertussis vaccine (DPTa) in Sweden

Potential health gain following the introduction of 3 dose acellular pertussis vaccine (DPTa) in Sweden

Introduction Pertussis is a contagious respiratory tract illness caused by a fastidious Gram negative coccobacillus, Bordetella pertussis (Edmunds et al., 2002). It is a vaccine preventable disease recognized world-wide as a highly infectious disease with significant associated childhood morbidity, presenting clinically as pneumonia, vomiting, choking spells, seizures,

encephalopathy and death (Galanis et al., 2006; Health Canada, 2005). Globally, an estimated 50 million cases of pertussis disease and 300,000 pertussis- related deaths occur annually (Halperin, 2001). In the past decade, an increase in the incidence and a shift of incidence towards older age groups has been observed in many developed countries (Zepp et al., 2011). Although pertussis is more severe in infants and young children, the increasing incidence in adolescents and adults is a major concern as adults are an important source of transmission to infants (Lee et al., 2004; De et al., 2000; Wood et al., 2008). Stopping pertussis immunization in a previously immunized population in Sweden resulted in the resurgence of the disease (Mortimer, 1988). The discontinued pertussis vaccination in 1979 resulted in 69% of cases in 19801985 occurring in children 16 years of age (Romanus et al., 1987). In the absence of an immunization programme 80% of surviving newborns would acquire pertussis in the first five years of life (Fine & Clarkson, 1984). Due to concerns about safety and efficacy of whole-cell pertussis vaccine (Romanus et al., 1987), diphtheriatetanus-acellular pertussis vaccines (DTPa) were included in the Swedish vaccination program at 3, 5 and 12 months of age in January 1996 following the completion of a number of clinical trials and the subsequent licensure of the vaccine (In Gothenburg and surroundings a catch-up campaign with a mono-component pertussis vaccine was given on its own as part of a clinical trial (Trollfors et al., 1995). Vaccination coverage rapidly reached more than 98% and an intensified clinical documentation of reported laboratory-confirmed pertussis in preschool children started in October 1997. There was a widespread decline in pertussis incidence throughout the country just four years after the introduction of DTPa in Sweden, the reported incidence of culture-confirmed pertussis being 8090% lower than before the DPTa introduction (Smi, 2013; Olin et al., 2003; Gustafsson et al., 2006). Full potential achievement of
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these vaccination program was highly through parents recognizing the need for vaccines as a means of mobilizing the body's natural defences and better prepared to seek vaccinations for their children; healthcare providers being aware of the latest developments and

recommendations; vaccine supplies and financing was made more secure and addressing the increasingly complex questions about safety, efficacy, and vaccine delivery (Smi, 2013). Sweden is a Scandinavian country in Northern Europe, bordered by Norway on the west, Finland on the east, connected to Denmark by a bridge-tunnel across the resund. It is the third largest country in the European Union by area, having a total population of about 9.5 million and population density of 21 inhabitants per square kilometre. The surveillance of communicable diseases is regulated by the Communicable Disease Act (CDA) and the Swedish Institute for Communicable Disease Control monitors 54 notifiable infectious diseases which include pertussis among others. The double reporting system is used emanating from the doctor treating the patient (Clinical notification) and the laboratory where the causative agent is identified (Laboratory notification) so as to increase the sensitivity of the surveillance (Smi, 2013). The incidence of pertussis in Sweden before and after introduction of DTPa vaccine The incidence rates of pertussis after the introduction of acellular pertussis vaccine were markedly lower compared to before the introduction (See graph 1). The history and trends of pertussis cases have been fully documented by Smi, 2013; Olin et al., 2003; Gustafsson et al., 2006. The annual incidence of culture-confirmed cases before introduction of DTPa was 89150 per 100,000, and a rapid drop occurred in 19961997 with the overall annual incidence reaching 1726 per 100,000 person years. A drastic drop of cases from 113 to 150 per 100,000 during 1992-1995 to 11 to 16 per 100,000 during 2001-2004 was observed. The reduction of the incidence of pertussis is most marked in the age groups covered by the three doses of DTPa at 3, 5, and 12 months of age (12-year-old in 1998 to 14-year-old in 2000), and the highest incidence occurred amongst infants who were either unvaccinated or received only a single dose of DTPa vaccine. The incidence among unvaccinated 02-month-old children was 235 per 100,000 person years compared to an average incidence of 337 per 100,000 person years in that age group during the 10-year period 19861995 before the introduction of DTPa (RR 0.70, 95% confidence interval (CI) 0.590.83). In children who had received only one
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dose of pertussis vaccine the incidence was 230 per 100,000 person years and including all children in the age group 34 months the incidence was 304 compared to an average incidence of 677 per 100,000 person years in that age group during 19861995 (RR 0.45, 95% CI 0370.54). A marked decline in the reported incidence occurred after the second and third dose of DTPa. After the second dose the incidence was 52 per 100,000 person years. In fully vaccinated children (three doses of DTPa) the incidence was 11 per 100,000 person years in children below 2 years of age and 37 per 100,000 thereafter. Reductions were also seen among older preschoolage children, in the age groups 2534 years of age and in the +35 age groups, but not among children aged 719 years.
180 No. PCR Or culture cases of pertussis per 100,000 population 160 140 120 100 80 60 40 20 0 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986

Introduction of DTPa vaccine

Year
Graph 1; Number of culture- and PCR-confirmed pertussis cases in all of Sweden per month from January 1986 to December 2004. Source: smi, 2013.
Sex Man Woman Unknown 2012 2011 2010 2009 2008 48.1 % 51.8 % 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997

44.6 % 45.7 % 55.3 % 54.2 % 0.1 % 0.1 %

45.8 % 44.8 % 54.1 % 54.8 % 0.1 % 0.4 %

49.5 % 48.0 % 44.6 % 47.6 % 45.0 % 46.8 % 46.0 % 48.2 % 47.3 % 47.2 % 47.5 % 50.4 % 51.9 % 55.2 % 52.3 % 54.9 % 52.8 % 53.9 % 51.5 % 52.6 % 52.5 % 52.1 % 0.1 % 0.2 % 0.1 % 0.1 % 0.4 % 0.1 % 0.3 % 0.1 % 0.3 % 0.4 %

0.1 % 0.1 %

Table 1; Comparison of pertussis cases between male and female in Sweden; smi,

2013

During the period 1997-2000, there were 145 hospital admissions due to pertussis cases among children born 1996 or later, showing an overall incidence of 18 hospitalizations per 100,000 person years. Most of these children were unvaccinated (n = 116), out of these, 97 including two deaths were under 3 months of age (incidence 158 per 100,000 person years under 3 months of age). There were 25 hospital admissions among children with pertussis who had received one dose of DTPa (incidence 61 per 100,000), and four among children above 5 months of age who had received two or more doses of DTPa (incidence 0.6 per 100,000). The duration of hospital stay was longer in the unvaccinated children compared to the vaccinated children: hospitalisation for more than 1 week was seen in 49% (57 of 116 hospital admissions) among unvaccinated children, compared to 24% (6 of 25) among children who had received one dose of DTPa, and none among the four hospitalized children who had received two or more doses of DTPa. Monitoring and surveillance of pertussis vaccination programs in Sweden Laboratory confirmed pertussis cases in Sweden have been voluntarily reported by local laboratories since 1988, but from 1997, notification of cases became mandatory. Clinical and culture confirmed cases of pertussis are reported to the Swedish Institute for Infectious Disease Control (SIIDC) through a national computer-linked reporting system. The primary case definition of infection is confirmed by culture or polymerase chain reaction (PCR) regardless of symptoms (Olin et al., 2003; Olin et al., 1997) and compiled by Smittskyddsinstitutet (Smi, 2013). The National Board of Health and Welfare is currently responsible for the vaccination programmes in the country. The national board in 2002 reschedule the vaccination programs by including a booster vaccination at school entry and leaving. A 4th dose was also introduced at 10 years of age so as to catch the first 7 birth cohorts primed with accelular pertussis at infancy .i.e those who will have already passed pre-school at the time of implementation of this new program (Rose, 2006). Issues that missed in the vaccination program Long-term effectiveness of this vaccination program showed increased incidence of pertussis among 7- to 8-year-olds, indicating waning of vaccine-induced protection. Expanded vaccination should have initially included adding a booster dose to existing childhood vaccination schedules (Gustafsson et al., 2006) as was done later (Smi, 2013). Vaccine boosting has had marked
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potential benefits in several European countries, Canada and USA (Edmunds et al., 2002; Matt et al., 2001; Iskedjian et al., 2010; WHO, 2001; Angela et al., 2012). Efforts should have been directed towards increasing or maintaining the coverage of infants with three doses of DPT vaccine at 90 per cent or higher; and strengthening the surveillance of pertussis morbidity. Vaccination schedule should have also included specific adult sub-groups who have a risk of transmitting the infection to the infant e.g. new parents, health care workers, etc. Socioeconomic impact of pertussis in Sweden Pertussis may be a prolonged, severe and frightening disease resulting in serious sequelae, causing a considerable distress to both the child and the family as a whole (Johnston et al., 1985). Due to the long- lasting course of the disease, the patients are exhausted, lose appetite and weight, and have disturbed sleep habits. Behavioural changes observed in pertussis patients include irritability, anxiety, and setbacks in development (Mark & Granstrom, 1992). The disease therefore becomes a family affair (Mortimer, 1990) because of social and economic consequences for the afflicted families. Episodes of choking, apnoea or cyanosis in ill children are distressing events for the entire family. A study reported disturbed sleep for 78% of parents, with 53% having to attend to the child 4 times or more each night (Mark & Granstrom, 1992). The economic consequences of the disease include expenses for medical visits and drugs, and the need to stay at home from work for a prolonged period to take care of the ill child. Meanwhile the cost of a non-hospitalised case of pertussis in Sweden is not documented, some European countries have been estimated at 22 per visit (Netton & Dennet, 1999) and a 10-day course of erythromycin at 4.40 (eBNF-36). Hospital stay due to pertussis would be on average 5 days at 297 (Netton & Dennet, 1999) per day plus additional follow up GP consultations, totaling 1529 per patient, again, about 12.5% of hospitalized cases require specialist care, experiencing on average 4 days paediatric ITU care for complications of pertussis at 1065 per day and 12 days general ward stay, totaling 7868 (Matt et al., 2001). In some studies, cost per QALY is estimated at 14,50070,000 range and the cost per case avoided is 400 or 3055 depending on the scenario assumed, however these are also influenced by the length and strength of protection assumed following naturally acquired pertussis (Matt et al., 2001). In the 1980s, the
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hospitalization rate attributable to pertussis in Sweden was 12 to 18 per cent for all ages) and the mean duration of hospital stay was 8 days for infants younger than 6 months, 6 days for children 611 months of age, and 4 days for patients older than 12 months (Romanus et al., 1987). The reduction of pertussis since the introduction of DPTa vaccine has therefore been of great value to Sweden.

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