National Consensus Conference on Pertussis
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Table of Contents | Executive Summary | Background 

Pertussis: Clinical Features and Diagnosis 

The most serious pertussis disease occurs in young infants, who may experience complications such as pneumonia, seizures and encephalitis and who are at the greatest risk of dying from pertussis. The symptoms are milder in older children and adults but include the characteristic whoop after paroxysmal cough, and possibly vomiting. Several tests are available for diagnosis: culture, direct fluorescent antibody testing, polymerase chain reaction (PCR) and serologic testing. Although culture has been the gold standard in the past, its sensitivity is affected by many factors. There is evidence that PCR is more sensitive, although the laboratory methods in use need to be standardized. 

Epidemiology 

The number of reported cases in Canada has increased from the early 1990s with peaks every 4 years. The greatest incidence has been among infants < 1 year of age, and the second highest rate at present is among children aged 10 to 14. There are epidemiologic data showing that the cohort of children and teenagers immunized between 1980 and 1992 with Connaught whole cell adsorbed vaccine is currently at greater risk of pertussis, because this vaccine provided poor protection and no acellular pertussis vaccine booster dose was given. The vulnerability of this cohort is reflected in the increasng age of cases over time. Waning immunity is an additional factor in this group. 

There is evidence from those provinces that introduced the acellular vaccine into their immunization program several years ago that it is having a positive impact on the number of cases reported. In British Columbia, the incidence of pertussis in infants and preschool children fell substantially after the vaccine came into use in 1997, as did rates of hospital admision in these groups. The incidence trends in that province over the 1990s have shown increases in mid-childhood, and by 2000 the proportion of cases reported in 10 to 14-year-olds was greater than that among infants or preschool children. Molecular surveillance of Bordetella pertussis strains in Alberta and Quebec indicates that new strains are emerging in these provinces, and there is a move away from the “old” vaccine types. 

In the U.S. there have also been increases in reported cases of pertussis in the last decade, and since the late 1990s the number of deaths, mainly in infants, has risen as well. The age groups to be affected by the greater burden of disease are 10 to 19 year olds and, to a lesser extent, adults aged 20+. Among infants who had received at least two doses of the acellular vaccine there was a levelling off in incidence rates in the mid 1990s. In a large, prospective randomized controlled trial in the U.S. the incidence rate of pertussis among subjects aged 15 to 65 was estimated to be between 370 and 860 cases per 100,000. A French study carried out to estimate incidence among adults reported a similar rate, at 884 cases per 100,000. In France, there is evidence of a shift in the spread of disease, from child-child to adult-infant transmission. Increases in reported cases in the U.K. have been most evident in those aged < 3 months, but it is believed that there is significant under-reporting. In a community study of patients aged 5 to 92 years with cough of > 3 weeks' duration, the incidence rate was estimated to be 330 per 100,000, whereas the official notification rate for that period was < 4 per 100,000. In Australia, the number of deaths rose sharply from 1986-95 to 1996-2002, and hospitalization data for 2001 indicate that the majority of serious illness occurred in infants < 8 weeks of age, i.e. the unimmunized. 

Immunization 

Although used in Japan for over 20 years, acellular pertussis vaccines have figured only relatively recently in the immunization schedules of other countries. In the U.K., a whole cell vaccine is used for the primary series, and a preschool booster dose of acellular vaccine was added in 2001. A whole cell vaccine is also given during infancy in France, but booster doses of acellular vaccine are now administered at 16 to 18 months and 11 to 13 years of age because of changing epidemiologic patterns. In Sweden, doses in the primary series and the booster dose (at 6 to 10 years) all make use of acellular vaccine. The immunization schedule in Canada consists of a primary series at 2, 4, and 6 months of age, and booster doses at 18 months and 4 to 6 years. Studies on the immune response to pertussis vaccines have shown that although the antibody response to vaccine wanes over time before being boosted by a further dose, the T cell count increases and remains elevated between vaccine doses. Acellular pertussis vaccines provide a better, longer lasting cellular immune response than whole cell vaccine. 

The efficacy of the acellular pertussis vaccine currently used in Canada, as estimated from clinical trials, is 85%. Hospital data from the IMPACT surveillance system in Canada provide evidence of the greater efficacy of the acellular vaccine: after 1998, when the vaccine was introduced, the ratio of hospitalized infants < 3 months of age to infants aged 6 months to 1 year (i.e. those who had received three doses of the new vaccine) increased dramatically. Patterns in reported cases among older children in Quebec since 1998 also support its efficacy. In international trials, acellular vaccines with three or more pertussis antigens have been found to be more effective than those with one or two antigens, but acellular vaccines have not been uniformly superior to whole cell vaccines in efficacy. Although they are associated with fewer adverse events than whole cell vaccines, acellular vaccines give rise to injection site reactions, such as swelling and tenderness, that increase substantially with the first booster dose given and again with the second. Whole limb swelling has also been reported. 

In a survey of provincial/territorial immunization programs in Canada, all jurisdictions were found to offer publicly funded Td (tetanus and diphtheria) vaccine between the ages of 14 and 16. With the new adolescent/adult formulation of acellular pertussis vaccine (Tdap), the hope is that universal immunization - possibly as a piggyback onto the existing Td schedule - would not only reduce morbidity in these age groups but would also increase herd immunity and reduce transmission to young infants. However, issues of timing and safety need to be resolved. Newfoundland and Labrador incorporated the adolescent pertussis vaccine into their tetanus/diphtheria booster dose in 1999-2000, but it is too soon as yet to gauge the effects. 

A modelling study of the cost-benefit of immunizing adolescents reported results favourable to the use of the vaccine, but given the caveats concerning the methodology it was recommended that the study be redone. With the use of a dynamic mathematical model and epidemiologic data from Quebec, it has been estimated that immunization of adolescents would lead to an overall reduction in disease of 15%, affecting primarily the age group 15-25 years rather than infants. 

Management of Pertussis 

The recommended therapy for pertussis in Canada has been erythromycin 40-50 mg/kg daily for 10 days to a maximum of 1 g, started within 3 weeks after onset of cough. Because of the side-effects of erythromycin, reduction in the duration of treatment and the use of alternative macrolides have been explored. Seven days have been found to be as effective (bacteriologic cure) as 14 days of treatment with erythromycin and give rise to fewer adverse events. Both clarithromycin and azithromycin have been shown to have equivalent effectiveness to erythromycin and fewer adverse events, but are more costly. Because pertussis is spread by close contact with the respiratory secretions of an infected person, chemoprophylaxis with erythromycin is usually instituted for household contacts and has been found to have a 67% efficacy in preventing bacteriologically confirmed secondary cases in that setting. However, its success in preventing clinical cases has been limited. Outside of closed settings, it is unlikely to be effective. Achieving outbreak control through chemoprophylaxis is hindered by the cost of the antibiotics and by the lack of understanding and appropriate action by general practitioners, who may not realize that pertussis in adults needs to be taken seriously for a variety of reasons. 

Recommendations 

After small group discussions, a number of recommendations were developed and presented for adoption in the plenary session. They covered several aspects of pertussis control: objectives of a pertussis control strategy, diagnosis, surveillance, treatment and chemoprophylaxis, and outbreak management. See page 20 for the full recommendations. 

BACKGROUND 

Pertussis, or whooping cough, results from an acute infection of the respiratory tract by Bordetella pertussis. Its main features are a paroxysmal cough ending in an inspiratory whoop and vomiting. The disease can lead to serious complications in young infants, and most of the deaths that occur are in this age group. Since the introduction of pertussis vaccine in Canada in the late 1940s, the number of reported cases has dropped dramatically, from 160 cases per 100,000 just before the introduction of the vaccine to < 20 cases per 100,000 in the 1980s. However, there has been an increase in the reported incidence during the 1990s and an emerging pattern, evident in several provinces (and in other countries), of a greater burden of disease in older age groups (10-14 years) and adults. As well, it is likely that pertussis is considerably under-reported in adults, who constitute an important source of transmission to infants and children. 

Acellular pertussis vaccine was introduced in Canada in 1997-98 and has replaced the previous whole cell vaccine. The immunization schedule consists of a primary series at 2, 4, and 6 months of age, and booster doses at 18 months and 4 to 6 years. An adolescent/adult formulation of the acellular vaccine has a lower antigen content and is recommended as the booster dose for adolescents (Canadian Immunization Guide 2002). 

The last consensus conference on pertussis was held in 1993. Because of the changes in pertussis incidence over the last decade, a shift in strategy may be required to improve control of the disease. This invitational meeting, organized by the Canadian Public Health Association in collaboration with the Centre for Infectious Disease Prevention and Control, Health Canada, was held to define national objectives on the prevention and control of pertussis. This report is an account of the proceedings of that meeting.  

Participants heard presentations from experts in various fields and subsequently broke into small groups to discuss specific aspects of pertussis, including objectives of a pertussis control strategy, diagnosis, surveillance, treatment and chemoprophylaxis, and outbreak management. The recommendations that emerged were brought back for further discussion by the whole group and were adopted by a consensus process (agreement by 90%+). They are not necessarily endorsed by Health Canada, the Canadian Public Health Association or provincial/territorial governments. 

Unrestricted education grants from Aventis Pasteur Inc and GlaxoSmithKline helped make this meeting possible. 

INTRODUCTORY REMARKS 

Dr. Arlene King 

The first mention of whooping cough (later called pertussis, meaning violent cough) in the medical annals was in 1540; the first epidemic was reported in 1578, and widespread epidemics followed in the 17^th and 18^th centuries. The memorable feature of the disease, the whoop, occurs during a paroxysm of coughing, when several powerful coughs following quickly one after the other hinder inspiration and produce the characteristic sound. In Canada, a whole cell pertussis vaccine became available in the 1940s, and the number of reported cases per annum has decreased by 71% since then; acellular vaccine was introduced in 1997. 

Participants will be asked to consider a number of issues that have recently arisen with regard to pertussis, such as the use of the acellular vaccine for infants and children, the new adolescent/adult acellular pertussis/tetanus/diphtheria vaccine that will replace the booster Td dose, and changing incidence trends over the last 10 years. All of these will have implications for pertussis control goals, immunization and surveillance strategies, treatment, and prophylaxis. 

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