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National Consensus Conference on Pertussis

Toronto

May 25-28, 2002

TABLE OF CONTENTS

Executive Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Introductory Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Pertussis: Clinical Features and Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Immunization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Management of Pertussis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Appendix 1: Notification and Early Treatment of Contacts . . . . . . . . . . . . . . . . . . . . . . . . . . 27

Appendix 2: List of Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

EXECUTIVE SUMMARY

Pertussis: Clinical Features andDiagnosis

The most serious pertussis disease occurs in younginfants, who may experience complications such aspneumonia, seizures and encephalitis and who are atthe greatest risk of dying from pertussis. Thesymptoms are milder in older children and adults butinclude the characteristic whoop after paroxysmalcough, and possibly vomiting. Several tests areavailable for diagnosis: culture, direct fluorescentantibody testing, polymerase chain reaction (PCR)and serologic testing. Although culture has been thegold standard in the past, its sensitivity is affected bymany factors. There is evidence that PCR is moresensitive, although the laboratory methods in useneed to be standardized.

Epidemiology

The number of reported cases in Canada hasincreased from the early 1990s with peaks every 4years. The greatest incidence has been among infants< 1 year of age, and the second highest rate at presentis among children aged 10 to 14. There areepidemiologic data showing that the cohort ofchildren and teenagers immunized between 1980 and1992 with Connaught whole cell adsorbed vaccine iscurrently at greater risk of pertussis, because thisvaccine provided poor protection and no acellularpertussis vaccine booster dose was given. Thevulnerability of this cohort is reflected in theincreasng age of cases over time. Waning immunity isan additional factor in this group.

There is evidence from those provinces thatintroduced the acellular vaccine into theirimmunization program several years ago that it ishaving a positive impact on the number of cases

reported. In British Columbia, the incidence ofpertussis in infants and preschool children fellsubstantially after the vaccine came into use in 1997,as did rates of hospital admision in these groups. Theincidence trends in that province over the 1990s haveshown increases in mid-childhood, and by 2000 theproportion of cases reported in 10 to 14-year-oldswas greater than that among infants or preschoolchildren. Molecular surveillance of Bordetellapertussis strains in Alberta and Quebec indicates thatnew strains are emerging in these provinces, andthere is a move away from the “old” vaccine types.

In the U.S. there have also been increases in reportedcases of pertussis in the last decade, and since the late1990s the number of deaths, mainly in infants, hasrisen as well. The age groups to be affected by thegreater burden of disease are 10 to 19 year olds and,to a lesser extent, adults aged 20+. Among infantswho had received at least two doses of the acellularvaccine there was a levelling off in incidence rates inthe mid 1990s. In a large, prospective randomizedcontrolled trial in the U.S. the incidence rate ofpertussis among subjects aged 15 to 65 was estimatedto be between 370 and 860 cases per 100,000. AFrench study carried out to estimate incidenceamong adults reported a similar rate, at 884 cases per100,000. In France, there is evidence of a shift in thespread of disease, from child-child to adult-infanttransmission. Increases in reported cases in the U.K.have been most evident in those aged < 3 months, butit is believed that there is significant under-reporting.In a community study of patients aged 5 to 92 yearswith cough of > 3 weeks’ duration, the incidence ratewas estimated to be 330 per 100,000, whereas theofficial notification rate for that period was < 4 per100,000. In Australia, the number of deaths rosesharply from 1986-95 to 1996-2002, and

National Consensus Conference on Pertussis 1

hospitalization data for 2001 indicate that themajority of serious illness occurred in infants < 8weeks of age, i.e. the unimmunized.

Immunization

Although used in Japan for over 20 years, acellularpertussis vaccines have figured only relativelyrecently in the immunization schedules of othercountries. In the U.K., a whole cell vaccine is used forthe primary series, and a preschool booster dose ofacellular vaccine was added in 2001. A whole cellvaccine is also given during infancy in France, butbooster doses of acellular vaccine are nowadministered at 16 to 18 months and 11 to 13 yearsof age because of changing epidemiologic patterns. InSweden, doses in the primary series and the boosterdose (at 6 to 10 years) all make use of acellularvaccine. The immunization schedule in Canadaconsists of a primary series at 2, 4, and 6 months ofage, and booster doses at 18 months and 4 to 6 years.Studies on the immune response to pertussis vaccineshave shown that although the antibody response tovaccine wanes over time before being boosted by afurther dose, the T cell count increases and remainselevated between vaccine doses. Acellular pertussisvaccines provide a better, longer lasting cellularimmune response than whole cell vaccine.

The efficacy of the acellular pertussis vaccinecurrently used in Canada, as estimated from clinicaltrials, is 85%. Hospital data from the IMPACTsurveillance system in Canada provide evidence ofthe greater efficacy of the acellular vaccine: after1998, when the vaccine was introduced, the ratio ofhospitalized infants < 3 months of age to infants aged6 months to 1 year (i.e. those who had received threedoses of the new vaccine) increased dramatically.Patterns in reported cases among older children inQuebec since 1998 also support its efficacy. Ininternational trials, acellular vaccines with three ormore pertussis antigens have been found to be moreeffective than those with one or two antigens, butacellular vaccines have not been uniformly superiorto whole cell vaccines in efficacy. Although they areassociated with fewer adverse events than whole cellvaccines, acellular vaccines give rise to injection site

reactions, such as swelling and tenderness, thatincrease substantially with the first booster dosegiven and again with the second. Whole limbswelling has also been reported.

In a survey of provincial/territorial immunizationprograms in Canada, all jurisdictions were found tooffer publicly funded Td (tetanus and diphtheria)vaccine between the ages of 14 and 16. With the newadolescent/adult formulation of acellular pertussisvaccine (Tdap), the hope is that universalimmunization – possibly as a piggyback onto theexisting Td schedule – would not only reducemorbidity in these age groups but would also increaseherd immunity and reduce transmission to younginfants. However, issues of timing and safety need tobe resolved. Newfoundland and Labradorincorporated the adolescent pertussis vaccine intotheir 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 immunizingadolescents reported results favourable to the use ofthe vaccine, but given the caveats concerning themethodology it was recommended that the study beredone. With the use of a dynamic mathematicalmodel and epidemiologic data from Quebec, it hasbeen estimated that immunization of adolescentswould lead to an overall reduction in disease of 15%,affecting primarily the age group 15-25 years ratherthan infants.

Management of Pertussis

The recommended therapy for pertussis in Canadahas been erythromycin 40-50 mg/kg daily for 10 daysto a maximum of 1 g, started within 3 weeks afteronset of cough. Because of the side-effects oferythromycin, reduction in the duration of treatmentand the use of alternative macrolides have beenexplored. Seven days have been found to be aseffective (bacteriologic cure) as 14 days of treatmentwith erythromycin and give rise to fewer adverseevents. Both clarithromycin and azithromycin havebeen shown to have equivalent effectiveness toerythromycin and fewer adverse events, but are morecostly. Because pertussis is spread by close contactwith the respiratory secretions of an infected person,

2 National Consensus Conference on Pertussis

chemoprophylaxis with erythromycin is usuallyinstituted for household contacts and has been foundto have a 67% efficacy in preventing bacteriologicallyconfirmed secondary cases in that setting. However,its success in preventing clinical cases has beenlimited. Outside of closed settings, it is unlikely to beeffective. Achieving outbreak control throughchemoprophylaxis is hindered by the cost of theantibiotics and by the lack of understanding andappropriate action by general practitioners, who maynot realize that pertussis in adults needs to be takenseriously for a variety of reasons.

Recommendations

After small group discussions, a number ofrecommendations were developed and presented foradoption in the plenary session. They covered severalaspects of pertussis control: objectives of a pertussiscontrol strategy, diagnosis, surveillance, treatmentand chemoprophylaxis, and outbreak management.See page 20 for the full recommendations.


BACKGROUND

Pertussis, or whooping cough, results from an acuteinfection of the respiratory tract by Bordetellapertussis. Its main features are a paroxysmal coughending in an inspiratory whoop and vomiting. Thedisease can lead to serious complications in younginfants, and most of the deaths that occur are in thisage group. Since the introduction of pertussis vaccinein Canada in the late 1940s, the number of reportedcases has dropped dramatically, from 160 cases per100,000 just before the introduction of the vaccine to< 20 cases per 100,000 in the 1980s. However, therehas been an increase in the reported incidence duringthe 1990s and an emerging pattern, evident in severalprovinces (and in other countries), of a greaterburden of disease in older age groups (10-14 years)and adults. As well, it is likely that pertussis isconsiderably under-reported in adults, whoconstitute an important source of transmission toinfants and children.

Acellular pertussis vaccine was introduced in Canadain 1997-98 and has replaced the previous whole cellvaccine. The immunization schedule consists of aprimary series at 2, 4, and 6 months of age, andbooster doses at 18 months and 4 to 6 years. Anadolescent/adult formulation of the acellular vaccinehas a lower antigen content and is recommended asthe booster dose for adolescents (CanadianImmunization Guide 2002).

The last consensus conference on pertussis was heldin 1993. Because of the changes in pertussisincidence over the last decade, a shift in strategy maybe required to improve control of the disease. Thisinvitational meeting, organized by the CanadianPublic Health Association in collaboration with theCentre for Infectious Disease Prevention and Control,Health Canada, was held to define national objectiveson the prevention and control of pertussis. Thisreport is an account of the proceedings of thatmeeting.

Participants heard presentations from experts invarious fields and subsequently broke into smallgroups to discuss specific aspects of pertussis,including objectives of a pertussis control strategy,diagnosis, surveillance, treatment and chemo-prophylaxis, and outbreak management. Therecommendations that emerged were brought backfor further discussion by the whole group and wereadopted by a consensus process (agreement by90%+). They are not necessarily endorsed by HealthCanada, the Canadian Public Health Association orprovincial/territorial governments.

Unrestricted education grants from Aventis PasteurInc and GlaxoSmithKline helped make this meetingpossible.


INTRODUCTORY REMARKS

Dr. Arlene King

The first mention of whooping cough (later calledpertussis, meaning violent cough) in the medicalannals was in 1540; the first epidemic was reported in1578, and widespread epidemics followed in the 17th

and 18th centuries. The memorable feature of thedisease, the whoop, occurs during a paroxysm ofcoughing, when several powerful coughs followingquickly one after the other hinder inspiration andproduce the characteristic sound. In Canada, a wholecell pertussis vaccine became available in the 1940s,and the number of reported cases per annum hasdecreased by 71% since then; acellular vaccine wasintroduced in 1997.

Participants will be asked to consider a number ofissues that have recently arisen with regard topertussis, such as the use of the acellular vaccine forinfants and children, the new adolescent/adultacellular pertussis/tetanus/diphtheria vaccine that willreplace the booster Td dose, and changing incidencetrends over the last 10 years. All of these will haveimplications for pertussis control goals, immuniza-tion and surveillance strategies, treatment, andprophylaxis.


PRESENTATIONS

Pertussis: Clinical Features and Diagnosis

Clinical Spectrum of PertussisAcross the Ages

Dr. Jussi Mertsola

Pertussis may be categorized according to stage: thecatarrhal stage, when there is cough, rhinorrhea andpossible fever; the paroxysmal stage, during whichthe whoop and vomiting after cough occur; and theconvalescent stage, consisting of gradual recoverywith possible set-backs. Complications are mostcommon in infants. In the U.S., 63% of infants < 6months of age required hospitalization; complicationsincluded pneumonia (11.8%), seizures (1.4%), andencephalopathy (0.2%), and the mortality rate was0.8%(1). In one U.S. study, 98% of infants who diedhad pneumonia, and 78% had not been vaccinated(2).Heininger et al(3) found that in 18% of 51 cases ofsudden infant death syndrome the results ofpolymerase chain reaction (PCR) testing werepositive for B. pertussis.

In Finland, there were 164 laboratory confirmedpertussis cases admitted to university hospitals in the1990s. About 70% were < 4 months old, 22% wereadmitted to the intensive care unit (ICU), and 8%required assisted ventilation. Comparison of pertussissymptoms in immunized and unimmunized childrenindicated that the whoop was present in 39% ofimmunized as compared with 56% of unimmunizedchildren, vomiting in 49% versus 65%, and apnea in8% versus 15%(4).

There is good evidence that vaccine efficacy decreaseswith time, possibly from 100% at 1 year down to 46%at 7 years(5). This is why there was a trend towardincreased pertussis incidence among older children,adolescents, and adults in the 1990s. In Finland, thewhole cell pertussis vaccine has been available since1952 and is given at 3, 4, 5, and 24 months, withabout 98% coverage. In the 1990s there was a 5-fold

increase in the incidence of pertussis among infants,who get the disease mainly from adolescents andadults. In 1999, 29% of laboratory confirmed cases inFinland were aged 20 years or older. Symptoms inadolescents and adults have included paroxysms(83% and 87% respectively), whoop (30% and 33%),vomiting (45% and 41%), and apnea (19% and37%)(6).

The State of the Art in Diagnosis ofPertussis: the Positive Predictive Valueof Symptoms in Children, Adolescentsand Adults, and LaboratoryConfirmation

Dr. Kathryn Edwards

Diagnostic methods for B. pertussis consist of directdetection, i.e. culture, direct fluorescent antibody(DFA) testing, PCR, and indirect detection, i.e.serologic methods using paired sera (from early andlater in the course of the illness), a single elevatedantibody titre, or high titres in family members. Inthe past, culture was the gold standard, but manyfactors influence its sensitivity. DFA provides rapidresults, but it has low sensitivity. PCR methods arenot consistent across laboratories in terms of samplepreparation, primer selection, detection systems andselection of controls. Enzyme linked immunosorbentassay (ELISA) is the basis for serologic methods.

Validation of PCR against serology, culture andsymptoms was carried out by Heininger et al(7) in alarge pertussis vaccine efficacy trial (among children)in Germany. Using a positive serologic result for B.pertussis as the standard, the overall sensitivity ofPCR was found to be 61% and the specificity 88%;PCR was more sensitive than culture. Comparison ofPCR results and clinical symptoms revealed thatduration of cough, presence of paroxysms, whooping


and/or vomiting, and clinical diagnosis of probable ordefinite pertussis were all significantly lesspronounced in children with negative PCR ascompared with positive PCR results. In acommunity-based study of the prevalence of pertussisamong 442 adolescents and adults it was found that20% had either laboratory confirmed pertussis orlaboratory evidence of pertussis, the latter basedprimarily on serologic criteria(8). The use of pairedserum samples may be problematic, in that the

specimen from the acute stage is often obtained late;use of a single specimen relies on cut-off levels thatmay be arbitrary. Information on levels of antibody topertussis antigens in a large sample of the generalpopulation could be used as age-specific referencevalues for serologic diagnosis. The CDC has carriedout such a survey to determine these levels.

Epidemiology

Epidemiology of Pertussis in Canada

Dr. Eleni Galanis

As measured from data obtained from the NationalDisease Reporting System and the Canadian Institutefor Health Information, the incidence of pertussis inCanada has increased since the beginning of the1990s, with peaks every 4 years. The average numberof reported cases across Canada in the 1990s was6,000 or 10 to 35 per 100,000 per year, the highestincidence being found among infants < 1 year of ageand the second highest currently among childrenaged 10 to 14. Possible reasons for the increasingincidence are

� a change in circulating strains of B. pertussis

� waning vaccine immunity

� a decrease in vaccination coverage

� low efficacy of the whole cell vaccine

� increased awareness and reporting.

The stable or decreasing hospital separation rates inall age groups during the same period suggests that atleast part of the increase in pertussis incidence is dueto increased awareness and reporting of the disease.Not all provinces/territories reported an increasedincidence in the early 1990s, but in all jurisdictionsthere were large pertussis outbreaks during differentyears; this may have led to an overall increase inpertussis incidence in Canada.

With respect to the acellular vaccine, introduced in1997, data from British Columbia, Alberta,Saskatchewan and Ontario show a positive impact, asillustrated by a decreasing incidence since 1998among 1 to 6-year-olds as compared with infants < 1year and 7 to 9-year-olds; the dip in 2000 among 7-year-olds (2 years after their booster dose of acellularvaccine); and the fact that the lowest incidence is inthe cohort that has received the most doses of thenew vaccine.

Epidemiology of Pertussis inBritish Columbia

Dr. Danuta Skowronski

In British Columbia, the gradual increase in reportedpertussis since the 1990s has been accompanied byoutbreaks of the disease occurring in 1990, 1993,1996 and 2000, each with a higher peak incidencethan the previous outbreak. In 1990, the highestproportion of cases occurred in children < 5 years ofage; in 1993, the pattern was similar, but theproportion among 5 to 9-year-olds had increasedsubstantially; in 1996, there were further increases inthis age group and also among 10 to 14-year-olds;and by 2000, the largest proportion occurred among10 to 14-year-olds. In 2000, both the proportion ofpertussis cases reported and the incidence weregreater among 10 to 14-year-olds than among infantsor preschool children.


Although requests for laboratory confirmation ofpertussis rose during 2000 in the 10-14 year agegroup, so too did the proportion of positive testresults, suggesting that increased awareness andindiscriminate laboratory requests were notresponsible for the greater incidence of disease.Neither is PCR testing likely to be the sole reason forrecent trends: even though this laboratory methodincreased the proportion of positive results across allage groups, the greatest proportion by either cultureor PCR was reported among pre-teens and teens. Theprotective effect of pertussis immunization waneswith time, and individuals aged 10 to 14 might beexpected to be more vulnerable to infection thanyounger children. However, the increasing rates inthe same age group over each outbreak, together witha declining incidence after age 12 during 2000, argueagainst waning immunity as an explanation for theepidemiologic pattern. On the other hand, a vaccinethat was suboptimal in its efficacy 10 years ago wouldbe expressed through a persistent cohort effect suchas the one noted.

The results of introducing the more efficaciousacellular vaccine in 1997 have been beneficial. Theincidence of pertussis among infants and preschoolchildren fell appreciably between 1996 and 2000, asdid rates of hospitalization (by half among infantsand one-quarter among preschool children).

Epidemiology of Pertussis in the U.S

Dr. Trudy Murphy

The National Notifiable Diseases Surveillance Systemin the U.S. is a passive system that has been inoperation since the 1960s, in which individual Statessend data on confirmed and probable cases ofnotifiable disease, including pertussis, to the Centersfor Disease Control and Prevention (CDC). Aconfirmed case is defined as one in which B. pertussishas been isolated, or as a clinical case with either apositive PCR result or a link with a laboratoryconfirmed case; a probable (clinical) case is definedas 14 days or more of cough with paroxysms, whoopor vomiting, with no other cause.

From the early 1990s there has been an increase inthe number of reported pertussis cases, ranging from< 5,000 cases per year in 1990 to 7,867 cases in 2000,and yet rates of immunization – vaccine given at 2, 4,6, 15 to 18 months and 4 to 5 years – have remainedhigh, in the 90%+ range for at least three doses ofeither acellular or whole cell vaccine. As well, thenumber of deaths (which occur predominantly ininfants) has been increasing since the late 1990s.

The acellular pertussis vaccine has been available forthe fourth and fifth doses in the immunizationprogram since 1992 and for the primary series since1996. Overall, the incidence or reported number ofcases has remained fairly stable among 1 to 4 and 5 to9-year-old children. Among infants 4 to 11 monthswho received at least two doses of the acellularvaccine there was a levelling off in rates from themid-1990s, whereas among younger infants withfewer doses this occurred later. The incidence ofreported cases among 10 to 19-year-olds and, to alesser degree, among adults aged 20+ has increasedduring the 1990s. It is unclear how much of theincrease among adolescents represents a real increaseor improvements in recognition, diagnosis andreporting.

The APERT Study

Dr. Joel Ward

The APERT study(9), sponsored by the NationalInstitutes of Health, was a prospective, randomizedcontrolled trial (double blind) that was carried out ateight sites in the U.S. to assess the incidence andclinical spectrum of pertussis in adolescents andadults as well as the efficacy and safety of theacellular vaccine in these individuals. One dose ofvaccine was administered to 2,781 subjects aged 15 to65, recruited between 1997 and 1999. Acellularpertussis vaccine was given in the experimentalgroup and hepatitis A in the control group. Allsubjects were prospectively followed and contactedevery 2 weeks for 2 years. If they reported a cough of5 days’ duration or longer this was evaluatedclinically and by culture, PCR, and serologic testing(acute versus convalescent specimens). Each subject


provided three to 10 blood specimens for serologicevaluation during the study to detect asymptomaticinfections.

Cough illness was found to be very common in bothgroups (about half of all subjects reported a coughlasting 5 or more days per year), with a meanduration of 24.4 days. There was no significantdifference between the vaccine groups in incidence ofcough illness. There were 10 cases of well-confirmedpertussis detected during the trial, as determined bypositive results on culture or PCR or by increases inantibody titres; all but one of the cases occurred inthe control group. The overall efficacy of thepertussis vaccine was estimated to be 92%. Pertussiscases as a proportion of reported cough illnessincreased significantly the longer the duration ofcough, i.e. the longer the cough continued the higherthe proportion of pertussis cases. Risk factors forpertussis were young age (< 30 years) and duration ofcough. Culture and PCR were relatively insensitive indiagnosis, even early in the illness at day 5 of cough.

The incidence of disease as determined in theunimmunized controls was 4 cases per 1,000 subjectsper year. This represents up to 1 million cases peryear in older individuals in the U.S. No seriousadverse events from the vaccine were reported,although local reactions were experienced, morecommonly by women than men.

Epidemiology of Pertussis in France

Dr. Nicole Guiso

In France, the whole cell pertussis vaccine, combinedwith diphtheria and tetanus toxoid and polio vaccine,has been in use since 1966, given at 3, 4, and 5months with a booster at 16 to 18 months;Haemophilus influenzae type B vaccine was added in1995. In 1985, only 86 cases of pertussis werereported, therefore the disease was discontinued as anotifiable disease and surveillance ceased. In 1991,however, a study carried out in a pediatric hospitalreported that the number of infants hospitalized forpertussis had increased and that there was a changetowards adult-infant rather than child-childtransmission(10).

In a subsequent national study(11), in 1993-1994,involving 22 pediatric hospitals (20% of the totalnumber in France), 316 index cases were reported, ofwhich 204 (65%) were aged < 1 year and 99 (33%)were < 3 months. Of 314 index cases, 230 (73%) hadnot been vaccinated, 98 because they were < 3months old. The resurgence of pertussis was not feltto be due to decreased vaccination coverage orvaccine efficacy. Since 1996, surveillance carried outin 43 pediatric hospitals across France has shownsimilar trends. In 1998, the immunization schedulewas changed to a primary series of whole cell vaccineat 2, 3, and 4 months, a first booster dose of acellularvaccine at 16 to 18 months, and an additional boosterdose of acellular vaccine at age 11 to 13 years.

A 1999 study to estimate the incidence of pertussis in

adults recruited 217 patients aged � 18 years whocomplained of cough lasting > 7 but < 31 days(12). Adiagnosis of pertussis was confirmed by culture, PCRor serologic detection of increased or decreasedanti-pertussis toxin IgG (by a factor of at least 2)between acute and convalescent serum samples. Atotal of 70 confirmed cases were found (32%), for anestimated incidence of 884 cases per 100,000.Antibiotic treatment did not modify the duration ofcough.

Booster vaccination doses given to adolescents andadults regularly throughout life would be the idealstrategy for reducing the burden of pertussis, but thisis not feasible for a number of reasons. Vaccination oftargeted groups, such as adolescents, adults incontact with infants, and vulnerable adults with otherhealth problems, is more likely to succeed.

Epidemiology of Pertussis in the U.K.

Dr. Natasha Crowcroft

In the U.K., a whole cell pertussis vaccine is given ina combined vaccine at 2, 3, and 4 months, and since2001 a booster dose of acellular vaccine has beenadded at age 3.5 to 5 years. Although there waswidespread concern among the public about theadverse effects of the vaccine in the late 1970s,vaccination coverage has since recovered and hasbeen over 90% for the last decade. The last epidemic


occurred in 1997, when 2,989 cases were reported; in2000 there was an all-time low of 712 cases. Theproportion of cases among infants < 3 monthsincreased during the 1990s. The number of deathsobserved varies according to the data source but hasbeen estimated at 9 per year from 1994 to 1999.

It is believed that the disease is substantiallyunder-reported – for instance, there are two to threehospital admissions for pertussis for every one casereported – thus enhanced surveillance and specialstudies are needed to improve data collection. Acommunity study conducted in 1996-97 investigatedpatients (age range 5-92) who presented with acutetracheitis or spasmodic cough of > 3 weeks’duration(13). Of 356 such patients, 58 were identifiedas having serologic and/or bacteriologic evidence ofpertussis, 32 (55%) of whom were known to havebeen fully vaccinated. This is equivalent to anincidence rate of 330 cases per 100,000 per year.(The official notification rate for the period understudy was < 4 per 100,000.) Of those aged 5 to 14years, 45% had evidence of recent pertussis infection,and of those 15 to 44 years old the proportion was28%. In a further study, carried out in a pediatricICU, it was found that 25 of 127 infants (20%)admitted had pertussis, only 3% of whom had beensuspected of having the disease(14). In 44% of cases theparents were responsible for transmitting theinfection, and in 32% it was a sibling. Taken together,these results indicate that the pertussis notificationrate is a vast underestimate, and that older childrenand adults are becoming infected and passing theinfection on to infants.

Epidemiology of Pertussis in Australia

Dr. Peter McIntyre

In Australia, there has been an increase in thepertussis notification rate from the early 1990s to thepresent, as recorded by the National NotifiableDisease Surveillance Scheme. The last epidemicoccurred in 1997, when the incidence rate reachedalmost 60 cases per 100,000 population.

With regard to the burden of disease, in a study of140 infants hospitalized for pertussis in the year 2001through the Australian Paediatric Surveillance Unit,the average hospital stay was 8 days, 18% requiredICU admission, and 3% died(15). Aboriginal babieswere over-represented. In a group of adults withreported pertussis(16), the median duration of coughwas 60 days, median number of visits to the generalpractitioner 3.7, and the median number of days inwork lost was 4 (equivalent to 15,000 lost work daysoverall in Australia). With regard to deaths, theannual rate rose sharply from 1986-95 to 1996-2002.From 1993 to 2001 there were 16 deaths, for anestimated annual mortality rate of 0.70 per 100,000(as compared with 0.60 in the U.K. during 1994-99and 0.32 in the U.S. during 1997-2000).

The proportion of reported cases in which serologicresults were positive has increased during the 1990s(New South Wales data). Clinical diagnosis is muchmore common in children < 5 years, whereas in thoseaged > 5, serologic methods have a greater impact onthe number diagnosed. Laboratory and notificationstudies have indicated that symptoms of pertussis inadults match the finding of high whole cell antibodylevels(17).

A primary series of pertussis vaccine is given at 2, 4,and 6 months and boosters at 18 months and 4 to 5years. Immunization with acellular vaccine has beenfunded for the primary series since 1999 and for thebooster doses since 1998. Hospitalization data for2001 show that more than a third of cases occurbefore 6 weeks of age and more than a half before 8weeks, i.e. in unimmunized infants. Since theintroduction of the preschool booster dose in 1995, 5to 9-year-old children showed a decline innotification rates after the 1997 epidemic, close to therates for 1 to 4-year-olds, whereas since 1999 and forthe first time in Australia the notification rate among10 to 14-year-olds has become higher than amonginfants. Possible options to address the highincidence rates among adolescents and the increasingnumber of infant deaths are to eliminate the fourth(18 month) booster dose so that the first dose afterthe 2, 4, 6 months primary series is at 4 years, butintroduce an adolescent booster; and to encourage


pertussis immunization in mothers, and possiblyfathers, at or shortly after the birth of a baby(“cocooning”).

Molecular Surveillance of Pertussis

Dr. Mark Peppler

Molecular surveillance is an essential tool todetermine trends in strain types and their relationwith disease and vaccines, for example, whether theuse of vaccines over time leads to the development ofresistant organisms. Three methods of molecularsurveillance are serotyping of isolates usingmonoclonal antibody to fimbrial antigens;pulsed-field gel electrophoresis (PFGE), used togenerate a genomic fingerprint of an isolate; and genetyping by PCR, particularly on pertussis toxin S1subunit and pertactin.

There are two types of fimbriae produced by B.pertussis, Fim2 and Fim3, and isolates may expressone or the other, or a combination of both, on theirsurface. There are some problems with the expressionof fimbriae in culture, but they are an importantantigenic marker: in the past, vaccine has had to be

modified to address the type of fimbriae produced bycirculating strains of B. pertussis. PFGE is used toseparate genomic DNA fragments that can vary insize from 50 to 200,000 kilobases. The technique wasused to analyze 3,700 isolates from Alberta andQuebec between 1985 and 1994. On the basis of thepulsed field results, 98 different patterns wereidentified, of which 80% were represented by 15different types. Although PFGE showed that the mostcommon strains were different in the two provinces(strains designated 1 and 2 in Alberta, strains 1 and 3in Quebec), it cannot define the characteristics of thestrains. Information from gene typing must be addedto explore these characteristics.

Pertactin and pertussis toxin S1 subunit are the genesthat have been investigated by gene typing in relationto virulence. Of the top 30 PFGE types from Albertaand Quebec, estimated numbers and proportions ofthe old and new pertactin and pertussis toxincombinations show that 47% overall represented newtypes, 36% represented old types, and 17% were intransition. Thus, in Alberta and Quebec at least, thereis a trend away from the old vaccine types, althoughit is debatable whether this is a result of vaccinepressure.

Immunization

Pertussis Schedule in the U.K.

Dr. Natasha S. Crowcroft

Children in the U.K. are given the whole cellpertussis vaccine in a combined form, DTwP-Hib,with meningococcus C and oral poliovirus vaccine(OPV) at 2, 3, and 4 months, and a booster dose ofacellular pertussis vaccine, DTaP, at the age of 3.5 to5 years (with MMR and OPV). Before 1990, theprimary vaccine schedule was 3, 5, and 9 to 10months. The new “accelerated” schedule wasintroduced in the interests of increasing coverage andreducing adverse events.

The preschool booster dose was included from 2001onward because of evidence of continuinghospitalizations and deaths in young children. Thedecision to opt for a 4-year rather than a 15-yearbooster was based on a modelling (dynamic)exercise, whereby the cost-benefits of the twointerventions were compared using a variety ofassumptions about direct and indirect costs, vaccineefficacy, herd immunity, incidence, hospitalizationdata and deaths. It was felt that if indirect protectionthrough herd immunity was more than 60% to 70%then a 15-year booster would be the appropriatechoice; when indirect protection is low, then thebooster dose is more beneficial at 4 years. The effectsof the booster dose at 4 years will be monitored, andif necessary that decision will be revisited.


Pertussis Schedule in France

Dr. Gaston De Serres (on behalf ofDr. Nicole Guiso)

A whole cell pertussis vaccine is used in France. In1998 the schedule was switched from a primaryseries at 3, 4, and 5 months with a booster between16 and 18 months to the primary series being given at2, 3, and 4 months, a booster dose of acellularvaccine at 16 to 18 months and a second acellularbooster dose at 11 to 13 years. Vaccine coverage ininfants is 96% and the efficacy is 94%.

Pertussis Schedule in Sweden

Dr. Patrick Olin

When the whole cell vaccine used in Sweden lost itspotency in the 1970s, routine vaccination of infantsagainst pertussis was discontinued. This was followedby a resurgence of the disease in the country. Thecurrent schedule for immunization against pertussisconsists of three doses in infancy of DTaP-Hib-polioat 3, 5 and 12 months (the third administered as amatter of policy after at least a 6 months’ interval),and a late fourth dose at 6 to 10 years of age. It is feltthat there is a better antibody response if the intervalbetween the first two doses is 2 months rather than 1month. There has been high vaccination coverage, atabout 98%, for the first three doses, and a dramaticreduction in the number of pertussis cases sinceacellular vaccination programs began. The countiesin Sweden are using a variety of different acellularvaccines, and this makes surveillance and estimationof efficacy problematic.

Perspectives on the Immune Responseto Acellular Pertussis Vaccines, IncludingCell- Mediated Immunity

Dr. Fred Zepp

The usefulness of a vaccine may be gauged by itsclinical efficacy, the generation of antibody responsesto it, and the cell-mediated immune response,achieved primarily through T cell helpers and/orcytotoxic T cells. Modern vaccine development

strongly concentrates on the interaction of thevarious components of the human immune system(mainly T cells, B cells and antigen presenting cells).The antigen-presenting cells (i.e. dendritic cells, Bcells) present antigen (e.g. vaccine antigen) to T cells.Depending on the type of antigen and the antigen-presenting cell, different patterns of T cell functionwill be activated, leading to the recruitment ofvarious other T cells having helper, suppressor andcytotoxic functions. These activated cells thenproduce cytokines (various interleukins and gammainterferon) that further amplify T cell reactivity,activate macrophages, facilitate immunoglobulinproduction, or enhance the action of cytotoxic T cells(killer cells).

To explore cell-mediated immunity in the laboratory,T cells are cultured from peripheral blood and thenchallenged with the antigens of interest. In response,the T cells proliferate and produce cytokines. Thecytokine production pattern of T cells can bemeasured by means of ELIspot analysis, ELISA orRT-PCR (reverse transcriptase PCR). Theselaboratory studies have shown that unvaccinatedinfants do not have specific antibodies to pertussisantigens(18). After the primary immunization coursethe infants develop antibodies, which wane throughthe second year of life. Booster vaccination reactivatesB cell memory and leads again to an increasedconcentration of pertussis-specific antibody. Theantigen-specific proliferative T cell response increaseswith the first dose of vaccine and, in contrast to B cellresponses, remains elevated even during the timewhen there are low levels of circulating antibodies.Booster vaccination further potentiates theantigen-specific T cell response. The findings suggestthat pertussis-specific T helper responses controlimmunologic memory, thus providing protectionbetween vaccinations. The T cell response afternatural infection is very similar to vaccine inducedresponses(19).

Comparison of immune responses in infants toacellular and whole cell pertussis vaccines shows thatacellular vaccines provide a better, longer lastingcellular immune response than whole cell vaccine.Overall, they are highly immunogenic for B and Tcells; they induce high concentrations of


antigen-specific antibodies and high rates ofseroconversion, as well as long-lastingpertussis-specific T cell responses.

Impact of the Acellular Pertussis Vaccineon Canadian Children Since 1997-1998

Dr. Gaston De Serres

The estimated efficacy of the adsorbed whole cellpertussis vaccine used in Canada has ranged between28% and 60%, whereas that of three doses of theacellular pertussis vaccine given in clinical trials was85%. The proportion of pertussis cases by age duringthe 1990s, when the whole cell vaccine was beingused, shows a shift in peak incidence, from thehighest incidence among infants in 1990 to a peakamong those aged 3 to 4 years in 1993 and, again,among children approximately 3 years older than thisin 1996. This has been taken to represent a cohorteffect resulting from the lack of protection in aproportion of infants vaccinated in 1990.

With regard to the acellular vaccine, data fromIMPACT (the pediatric hospital-based surveillancesystem) for 1990 to 2001 indicate that, for infantsadmitted to hospital because of pertussis, the ratio ofthose aged < 3 months (i.e. not vaccinated) to those 3to 5 months of age did not change after the acellularvaccine had been introduced, in 1998. However, theratio of infants < 3 months to infants 6 months to 1year (i.e. those who had received three doses ofvaccine) did increase dramatically after 1998. Thus itappears that with the use of the new acellular vaccinethe number of older infants hospitalized has beenreduced. Data from Quebec on the number ofpertussis cases reported according to age also showthis change in ratios after 1998. In terms of olderchildren, the reported rates per 100,000 in Quebecwere considerably higher among 3 to 5-year-oldchildren than 9 to 11-year-olds up to about 1997, butafter 1998 the rates tended to converge, and from2000 onward the rates among 3 to 5-year-olds havebeen lower, as would be expected from the boosterdose of acellular pertussis vaccine they received in1998.

The use of acellular pertussis vaccine has reduced therisk of pertussis in infants and children. The groupprotected by this vaccine will be moving intoadolescence in the next few years and may still be atdecreased risk. The group that received only wholecell vaccine remains vulnerable now and wouldbenefit the most from an adolescent booster dose ofacellular vaccine. This cohort is currently aged from10 to 17-22 years, depending on the year ofintroduction in the different provinces.

Efficacy of Acellular Pertussis Vaccines inInfants and Duration of Protection

Dr. Patrick Olin

Many different types of acellular pertussis vaccinewith from one to five antigen components have beenevaluated in efficacy trials and compared with wholecell vaccines. Although the overall antigen level maybe similar among vaccine types, the amounts ofindividual antigens – for instance, pertussis toxoid –vary widely. The conclusions of a Cochrane review ofrandomized controlled trials (RCTs) were thatacellular pertussis vaccines with three or morepertussis antigens were more effective than thosewith one or two antigens(20); they were more effectivethan one whole cell vaccine but less effective thantwo others; and they showed fewer adverse effectsthan whole cell vaccine. It is important to note thatthere are a few whole cell vaccines with high efficacy.The greater efficacy of multicomponent over singlecomponent vaccines has been questioned by someauthors, who argue that the result is an artifact of theserologic criteria used(21).

With regard to duration of protection, activesurveillance in an Italian trial of two types ofthree-component acellular vaccine showed nodifference between the vaccines during the first 6years of life, and it was concluded that efficacy wasmaintained over 5 or 6 years(22). In a comparison of afour-component acellular pertussis vaccine and awhole cell vaccine given at 3, 4.5, 6 and 18 months ofage in German trials(23), overall cough rates weresimilar in both groups, and the calculated efficacyover 6 years of follow-up was 89% for the acellularvaccine and 92% for the whole cell vaccine.


The incidence of pertussis in Sweden rose to highlevels after the discontinuation of routine vaccinationin 1979. With the introduction of acellular pertussisvaccine in 1996 there was a rapid drop inculture-confirmed cases from 1996 to 1998. Beforethe vaccine was in use, most of the disease burdenoccurred in 2 to 4-year-old children, whereas peakswere evident in the higher age groups after itsintroduction. Analysis of vaccine failures shows thatat 6 to 7 years of age there is a clear increase in thenumber of failures particularly with thethree-component and five-component acellularvaccines, suggesting that there is waning immunityafter the primary dose and a possible need for apreschool booster dose.

Vaccine Safety: Risk with Multiple Dosesof Acellular Pertussis Vaccine

Dr. Scott Halperin

Although the rate of adverse events during theprimary series of pertussis vaccination does notincrease with succeeding doses, it has been foundthat the risk of injection site reactions is higher withsubsequent booster doses.

After the booster dose at 18 months, redness,swelling and tenderness have been found to increasesubstantially as compared with reactions to thevaccine in the primary series(24). Systemic reactions,such as fever, crying, irritability and drowsiness, onthe other hand, tended to decrease with the boosterdose. The fifth consecutive dose, at 5 years of age,resulted in further increases in local reactions overthe 18 month dose, from 35% to 60% of recipients forredness and 18% to 70% for swelling, although therewas a reduction in tenderness(25). A study of 356children given a variety of vaccine types found thatalthough five doses of acellular vaccine and five dosesof whole cell vaccine resulted in similar proportionsof cases reporting redness at the injection site, theacellular vaccine gave rise to fewer systemic adverseevents(25). A U.S. study has also shown increasedredness and pain with the fifth dose of a variety ofacellular pertussis vaccines(26). Whole limb swellingafter three doses of DTaP has been reported inGermany and subsequently in a solicited adverse

event cohort (2.5%) and an unsolicited adverse eventcohort (0.5%)(27). With regard to adolescent and adultstudies, although redness and swelling occur withadministration of Td vaccine, addition of the acellularpertussis component does not lead to higher rates ofthese reactions(28).

The mechanism of injection site events remainsunclear, but may be related to IgG antibody levelsand cell-mediated immunity. Further research isrequired on this issue as well as on optimalscheduling and dosage.

Td Coverage in Adolescents and inAdults: Could Pertussis Piggyback on theTd Booster Program?

Dr. Karen Grimsrud

Acellular pertussis vaccine is currently combinedwith tetanus and diphtheria toxoids in the childhoodimmunization schedule. One way of increasingprotection against pertussis in adolescents and adultsmight be to include acellular pertussis vaccine withthe Td booster dose that these groups receive.

A survey of provincial/territorial immunizationprograms revealed that all jurisdictions offer publiclyfunded Td or TdaP between the ages of 14 and 16years, either as a school program (10 provinces/territories) or given primarily by a physician(Ontario), or both. Newfoundland and Labrador,Nunavut and the Northwest Territories use TdaP.Information on coverage rates is collected only inNewfoundland/Labrador and Nova Scotia (95% and96% respectively); other jurisdictions’ estimatedcoverage ranges from 75% to 95%.

The results of two surveys (Aventis Pasteur, 2002,and the BC Centre for Disease Control, 2002) ofadult tetanus coverage indicate that an estimated 64%of adults had been vaccinated, about half within theprevious 10 years, primarily because of recent injury(64%) or for anticipated travel (12%). Adults receivedinformation about immunization from the media(51%) and their family doctor (43%), and 92% agreedthat they would be vaccinated if this was recommen-ded by their doctor. Other factors likely to influencetheir decision were knowledge about the severity of


the disease in adulthood, and exposure and trans-mission patterns; the low risk of side effects of thevaccine; the protection it would afford young infantswith whom they might be in contact; and recommen-dation by a doctor or public health nurse.

Provision of a booster dose of acelullar pertussisvaccine, therefore, would fit well with the usual Tdbooster dose in adolescence (and in somejurisdictions already does). In adults, uptake could beincreased by public awareness through the media,encouraging physicians to recommend and providevaccine, and offering vaccine during routine contactwith public health, e.g. during infant immunization.

The Newfoundland Experience inImplementing the Adolescent Program

Ms. Cathy O’Keefe

Because of the recommendation of the NationalAdvisory Committee on Immunization (NACI)supporting adolescent acellular pertussis vaccinationand the apparent shift to older age groups of reportedpertussis cases, Newfoundland and Labradorintroduced TdaP into its immunization program forgrade 9 children in 1999-2000. Since 1999, 18,000have been immunized, for an overall rate of coverageof 95%.

A survey of public health nurses (n = 82) in 2000revealed that 67 (82%) had previous experience withthe TdP program and 67 had administered 25 ormore doses. In 2002, seven communicable diseasecoordinators, with input from public health nurses,reported that most of the staff were pleased with theinformation materials on TdaP provided for parentsand that the post-immunization tear-off sheet wasuseful. It was felt that better communication, forexample, through the media, would have helped inimplementing the program in the community.Experienced nurses reported spending more time inpreparing information in the first, but notsubsequent, years of the program; they also needed toexplain the program to other health careprofessionals.

The adverse effects of the vaccine have consisted oftwo official reports of adenopathy, which weredeemed not to be associated with the vaccine, sevenofficial reports of swelling and discomfort at theinjection site, and one sterile abscess.

Since the number of pertussis cases reported hasdecreased from the peak incidence in 1994, it isdifficult to demonstrate any effect of the newprogram at this time. Enhanced surveillance ofpertussis will continue, with review particularly oncethe cohort immunized with acellular pertussisvaccine during childhood reaches the age of 15.

Various Strategies for Adolescent andAdult Immunization

Dr. Scott Halperin

With the increased incidence of pertussis amongolder children and adults in many jurisdictions, thegoal of pertussis control – to reduce its incidence andsevere morbidity among young children – asarticulated by NACI(29) may need to be revised. Thecurrent immunization strategy does control thedisease in young children but does not address theproblem in older age groups and in unimmunizedinfants < 2 months of age.

An alternative strategy is to provide universalimmunization for adolescents and adults. Ideally, thiswould not only reduce morbidity in these age groupsbut also develop herd immunity and reduce trans-mission to young infants. Problematic areas with thisstrategy are the appropriate timing of the immuniza-tion, the lack of a monovalent acellular pertussisvaccine, and the safety of administering a sixth doseof the vaccine.

Selective immunization aimed at protecting veryyoung infants would target pregnant women, closecontacts of newborns, and health care and child careworkers. The challenge associated with vaccinatingpregnant women is that the safety of acellularpertussis vaccine in pregnancy is unknown, as is theduration of protection and the effect of women’s


increased antibody levels on their infants’ immuneresponse to subsequent vaccination. Targeting closecontacts of newborns, or “cocooning”, may not beeasy to implement, particularly as the target groupwould be difficult to define. Protection of health careand child care workers carried out to benefit younginfants and children might run into objections tomandatory immunization from organized labour,particularly as there are few data to support such amove.

In summary, there are many unknown variables inthe choice of a different immunization strategy. It hasto be decided which are the most important variablesrequiring further information before the choice canbe made.

Cost Benefit of Adolescent andAdult Immunization

Dr. Philippe De Wals

There have been a number of studies to evaluate theeconomic effect or cost-benefit of the new acellularpertussis vaccine in Canada. The most recent one, byHemels et al, modelled the epidemiologic andeconomic consequences of an additional booster doseof acellular pertussis vaccine for adolescents inOntario(30).

The model followed a cohort of 144,000 adolescentsaged 12, who were given a booster dose of acellularpertussis vaccine (combined with diphtheria andtetanus toxoids) at the same time as hepatitis Bvaccine and were followed over the course of the next10 years. The current practice is to give three doses ofhepatitis B vaccine at the age of 12 years anddiphtheria-tetanus vaccine at the age of 14 years. Allsubjects had received five doses of whole cellpertussis vaccine in childhood. Estimates of theburden of disease were taken from Canadian studiescarried out during 1994 to 1998. An under-reportingfactor of 9 was used. Productivity losses were given asan average of 5 days’ work lost by parents ofhospitalized children and 8 hours of work lost byparents of non-hospitalized children. Vaccine efficacywas assumed to be 85% over 10 years, and programcoverage was predicted to be 95%.

From the Ministry of Health perspective, it was foundthat the new program would result in a yearlyadditional cost of $0.20 per child and a cost of $62.40per pertussis case avoided. The overall outcome interms of vaccine purchase was an estimated increasein costs of $2.1 million. However, there was areduction in the costs associated with vaccineadministration (–$1.1 million), disease burden (–$0.7million) and productivity lost (–$2.5), resulting in anet saving of $2.3 million from a societal perspective;4,500 cases of pertussis would be prevented.

The study methodology had many problems, and itappears that a new cost-effectiveness analysis shouldbe done. Among other problems, the modelunderlying the study described is a linear,deterministic one that takes no account of the cyclicalnature of pertussis, the possible indirect effect of thevaccine in reducing transmission, or the waning ofimmunity after vaccination. A dynamic model mightbetter mimic the long-term epidemiology of thedisease and evaluate the economic consequences ofadolescent vaccination.

Expected Impact of the DifferentStrategies to Immunize Adolescents andAdults: Mathematical Approach

Dr. Babak Pourbohloui

The dramatic recent increase in reported cases ofpertussis in Quebec along with the increasedincidence of the disease among adults prompted amathematical modelling approach to assess differentimmunization strategies for adults and adolescents. Itwas decided to start the investigation by looking atthe pre-vaccine era, when the population acquiredimmunity through exposure to B. pertussis, and tochallenge the standard assumption that suchimmunity lasted for 20 years. Data from thepre-vaccine era indicate that only a small proportion,< 2%, of reported cases were adults, whereas ifacquired immunity lasted for only 20 years thereshould be many more adults with symptomaticdisease for a second time.


The mathematical model assumes that in thepre-vaccine era infants are fully susceptible until theybecome infected, and at the end of the episode ofpertussis they move to the fully protected category.However, their immunity wanes with time, and theymove to a lower level of immunity in which they aresusceptible to boosting by infection; they loseimmunity again and again in this way until theybecome fully susceptible once more. With theassumption that acquired immunity lasts for 20 years,50% of the infected population would be expected tobe adults. In order to achieve a result closer to the 2%actually observed it is necessary to increase theduration of immunity as well as the number ofintermediate loops of lower immunity followed byboosts from infection. This was accomplished byadding new compartments to the model in order tobetter simulate the different levels of immunityoccurring after disease. With the assumptions of 50

years of acquired immunity and 10 intermediateloops of mild infection, the model simulates resultsconsistent with the pre-vaccination notification data.The model also incorporates post-vaccine compart-ments and vaccine-related waning immunity.

The overall conclusions were that the resurgence ofpertussis in the 1990s was largely due to a poorlyprotective vaccine, although even with an effectivevaccine there will be a shift to higher age groupsbecause of the intrinsic properties of the dynamics ofpertussis, rather than because of vaccine properties.Remaining with the current schedule and vaccine willresult in continued decreases in the number of cases.Immunization of adolescents would lead to an overallreduction of 15%, affecting primarily the age group15-25 years rather than infants. Introduction of adultimmunization based on the current Td boosterschedule would have little impact.

Management of Pertussis

The Treatment of Pertussis: Old andNew Macrolides

Dr. Scott Halperin

Antibiotics eradicate B. pertussis from thenasopharynx but have no effect on the clinicalsymptoms or course of pertussis unless given in theearly stages. They are therefore prescribed more forcontrol of transmission than for individual benefit.Erythromycin (preferably estolate) 40-50 mg/kg dailyfor 10 days to a maximum of 1 g (for 14 days to amaximum of 2 g in the U.S.) is the recommendedmacrolide in Canada, and this should be startedwithin 3 weeks after onset of cough. Cotrimoxazolecan be used if erythromycin is not tolerated.

The efficacy of erythromycin has been demon-strated(31). However, it is not well tolerated, andadverse gastrointestinal effects are reported moreoften after 14 than 7 days of treatment. In an RCT of7 days versus 14 days of erythromycin estolate for

children (and their household contacts) with cultureconfirmed pertussis, it was found that 7 days oftreatment were as effective as 14 days in terms ofbacteriologic cure (negative culture after treat-ment)(32). Adverse events were less common with the7-day course of treatment; however, there was nodifference in compliance rates between the twoschedules.

Two newer macrolides, clarithromycin andazithromycin, have been compared witherythromycin in two RCTs. In the first, culturepositive subjects (n = 62) were given eitherclarithromycin (15 mg/kg daily) for 7 days orerythromycin estolate (40 mg/kg daily) for 14 days(33).The two drugs were found to be equally effective, butclarithromycin was better tolerated and resulted inhigher compliance rates. In the second study,comparing the same schedule of erythromycinestolate with 5 days of azithromycin (10 mg/kg onthe first day and then 5 mg/kg daily for 4 days) in 114


subjects, the results were similar, i.e. compliance withazithromycin was better because of fewer adverseevents, although it was no more effective thanerythromycin in treating pertussis (unpublished data:Halperin S, Langley JM, Boucher F for PICNIC). Thecomparative cost of the drugs – erythromycin beingtwo to four times cheaper than clarithromycin andazithromycin – may be a factor in the treatment ofchoice.

Effectiveness of Prophylaxis

Dr. Gaston De Serres

Pertussis is spread by close contact with therespiratory secretions of an infected person, andwithin households the secondary attack rate tends tobe higher in younger age groups. An RCT(34) hasshown a 67% efficacy of erythromycin prophylaxis inpreventing culture positive pertussis in householdcontacts, but its clinical impact was very limited.Epidemiologic studies also suggest that chemo-prophylaxis provides some benefit. However, it mustbe started as soon as possible after the onset of coughin the primary case: the secondary attack rate hasbeen found to increase from 11% when prophylaxiswas initiated within 21 days of cough onset to 29% ifprophylaxis was delayed beyond 21 days(35). Whendelayed by 21 days or more the secondary attack ratewas similar in those with and without prophylaxis.

There may be delay in the use of prophylaxis if thetime to diagnosis is long, either because the primarycase did not consult a physician straight away, thephysician did not consider a diagnosis of pertussis, orlaboratory results were not available quickly. Deeks etal. found that even in the presence of four symptomsof pertussis, physicians diagnosed the disease in only44% of cases(36). Even after diagnosis, householdcontacts may not willingly undergochemoprophylaxis if the cost of a new macrolide ishigh (e.g. clarithromycin) or the drug carries the riskof adverse events.

There is little evidence for the efficacy of prophylaxisoutside household and closed settings – for example,in the classroom. However, household contactsshould be targeted and possibly children in home daycare settings, particularly if there are very younginfants present in both cases.

Prophylaxis may prevent some cases, but it should beused selectively because of the its limited positiveimpact.

Current Status and Problems withOutbreak Management:Perspective from the Field

Ms. Karen Pielak

A survey of public health nurses and medical officersof health has highlighted several areas of frustrationthat these health professionals experience whenfollowing up pertussis cases and contacts. Respon-dents were consistent in stating that 30 to 60 minuteswas the time required for each index case, and 15 to30 minutes per close contact. With an average of 10to 12 contacts per case the process can take up to 4hours altogether. Getting in touch with contacts isvery time-consuming, and maintaining confiden-tiality (with regard to the name of the case) can bedifficult.

Other delays are those arising from laboratoryinvestigation – either because of constraints onresources or because general practitioners do notconsider pertussis in their differential diagnosis anddo not order the appropriate tests at an early stage –and case reporting. Delays are likely to result inincreased transmission, until contacts are givenchemoprophylaxis. The drugs used for chemo-prophylaxis are a high cost for some families, andmany individuals are not willing to take antibioticswhen they have no symptoms, particularly if thereare side effects. With regard to immunization, it isdifficult to ascertain the status in certain childrenwithout an immunization registry in place. Updatingthe immunization schedule for contacts of pertussis


cases may be complicated by the fact that there isonly a combined acellular pertussis vaccine atpresent, and extra doses of diphtheria and tetanustoxoid may not be warranted. A further source offrustration is the lack of understanding on the part ofsome community physicians that pertussis is a healthconcern for adults as well as children, particularly asadults may be the ones most likely to transmit theinfection.

Suggestions for improved outbreak control includecovering the cost of chemoprophylaxis in order toincrease compliance, using prescriptions forantibiotics pre-signed by medical officers of health asa means of expediting chemoprophylaxis, andreserving chemoprophylaxis for individuals at greaterrisk of the complications of pertussis or those whoare in contact with unimmunized children or infants.


RECOMMENDATIONS

Goals

It was agreed that, given the information presentedduring the last 2 days, the goals of the pertussiscontrol strategy, as formulated at the 1993 consensusconference, are inadequate for the presentcircumstances and should be changed to thefollowing.

1. The goal of the pertussis control strategy is todecrease morbidity and mortality from pertussisacross the entire life span.

� Given the current state of knowledge, it isunclear whether elimination is achievable.

2. Protection of adolescents and adults is a worthygoal for the benefit of these cohorts themselves.

� It is not clear whether a collateral benefit ofprotection of infants would be achieved.

Priorities, Methods and Conditions

3. It is necessary to prioritize efforts to controldisease in various cohorts.

� Improve control in infants and youngchildren.

� Control pertussis in adolescents (by use ofuniversal adolescent immunization).

� Develop and implement effective strategiesfor control of pertussis in adults.

4. There is a priority to ensure that the pertussisimmunization schedule maximizes safety,effectiveness and efficiency.

� number of doses

� interval between doses

Factors that must be taken into account in makingchanges to the immunization schedule in order toimprove pertussis control are the possible adverseevents associated with multiple doses, the duration ofimmunity, other antigens given concurrently, thecost and logistics.

If the primary dose were to be accelerated in order toprotect infants at an earlier age, then the effect of thison other vaccines now given at the same time wouldneed to be considered. The lack of a monovalentacellular pertussis vaccine limits the choices. TheWorld Health Organization has a recommendationnot to immunize until after the first month.

Routine immunization of adolescents with the newadolescent form of acellular pertussis vaccine hasbeen recommended by NACI. One possibility wouldbe to provide the adolescent booster dose with thetetanus and diphtheria boosters, another would be togive it with hepatitis B vaccine. The best way ofachieving pertussis control in adults, for instancethrough immunization of new parents, is a subject forresearch.

Targets and Measurable Outcomes

The difficulty in setting quantifiable targets for acyclical disease like pertussis was acknowledged.

5. The ultimate target should be decreased diseaseoutcome.

– Improved surveillance may affectachievement of pertussis controloutcomes.

� Decrease the number of deaths frompertussis to zero.


� Decrease rates of hospital and ICU admissionamong young infants.

– Precise targets and timing to bedetermined by future research, with thegoal of having a strategy in place by 2008.

� Reduce the reported incidence of pertussisamong older children and adolescents to atleast the levels present in preschool-agedchildren.

6. Process outcomes: immunization should bedelivered on time.

� At least 95% of infants should receive thefirst dose of pertussis vaccine before 3months of age.

� At least 95% of infants should receive twodoses of pertussis vaccine by 5 months ofage.

� At least 95% of children should receive otherrecommended pertussis vaccine doses at therecommended age (within 3 months).

Laboratory Diagnosis

7. Polymerase chain reaction (PCR) should beestablished as the new gold standard fordiagnosis within 3 years.

� Two sets of primers should be used.

� External proficiency testing should be inplace to ensure quality control.

8. A system should be established for selectiveperformance of culture for strain typing,antibiotic sensitivity testing, and identification ofBordetella parapertussis and B. holmseii.

9. There should be support for the development ofcriteria for serologic diagnosis.

10. International reference sera and referenceantigens should be available.

11. An international consensus conference onpertussis diagnostic methods should be held.

� PCR

� serology

� pulsed-field gel electrophoresis

� specimen collection, handling and transport

Surveillance

Surveillance was defined as follows:

The timely collection, analysis anddissemination of information that leads topublic health action and/or hypothesisgeneration.

General

12. Data fields submitted nationally should bestandardized and applied consistently acrossCanada (i.e. there should be harmonization).

� Required parameters are age, sex, onset,outcome, method of confirmation, clinicalpresentation.

� Ideally, there should also be information onvaccine status.

13. Data fields should be specific enough to allowvalid and useful analysis and interpretation.

– i.e. non-aggregated age information inyears and/or months

14. Support for infrastructure for local public healthis required in order to ensure that there isadequate case investigation and data entry.

15. Linked disease and vaccine registries are apriority for development and implementation(e.g. to connect with individual level vaccinestatus).

Routine Disease-related Surveillance

The purpose of routine disease surveillance is tomonitor age-related trends in incidence, morbidityand mortality and to permit outbreak recognition.

16. Pertussis should be notifiable in all provinces andterritories by both laboratories and clinicians.


17. The 2000 revised case definition* should beadopted, except for reporting of only laboratoryconfirmed cases (see next item).

18. National reporting of pertussis should be ofclinical and confirmed cases, with an indicationof the method of confirmation.

19. The case definition should be revised to includeapproved laboratory methods that have beenvalidated and standardized as developed.

20. Intermittent statistical review of hospitalizationand mortality data should be carried outroutinely.

21. IMPACT (Immunization Monitoring Program –Active) should be recognized and supported asan important component of routine pertussissurveillance.

Routine Vaccine-related Surveillance

22. A system for accurately monitoring annualvaccine coverage should be established andmaintained in each jurisdiction.

� minimum at 24 months and other agesspecified in the objectives

� additional age groups to be added accordingto changes in vaccine schedule

23. Standards and data fields for assessing vaccinestatus should be developed and appliedconsistently across Canada (e.g. What does “upto date” mean?)

24. IMPACT surveillance and routinevaccine-associated adverse event reporting on atimely basis should be maintained to effectivelymonitor vaccine safety and ensure publicconfidence.

Special Disease-related Surveillance

25. Active surveillance initiatives should beestablished in selected jurisdictions to assess theduration and effectiveness of the entire pertussisimmunization program (including the newadolescent program).

26. Surveys or enhanced surveillance projects shouldbe conducted to calibrate the sensitivity of thepassive surveillance system.

27. Enhanced surveillance projects should beimplemented to assess the impact andconsequences of pertussis in adults andadolescents.

28. Periodic enhanced mortality tracking frommultiple sources should be implemented tobetter gauge this indicator (e.g. usingcapture-recapture methods).

29. All undiagnosed deaths in infants and SIDS(sudden infant death syndrome) cases should beinvestigated for pertussis.

30. Circulating/outbreak strains should becharacterized to monitor the evolution of theorganism.

31. Special studies should be established to assessparticular vaccine-related risks in adolescents andadults (e.g. to monitor injection site reactions)and the cumulative effect of multiple doses.

32. An initiative to monitor knowledge, attitudes andbeliefs among members of the public and healthcare workers should be established both beforeand after the introduction of an adolescent/adultprogram, related to

� pertussis disease

� immunization against pertussis


* Confirmed case:Isolation of B. pertussisPositive PCR for B. pertussisEpi link with laboratory confirmed case and

paroxysmal cough orcough with vomiting or apnea orcough with inspiratory whoop

Treatment and Prophylaxis

Treatment

33. Any of the following should be used fortreatment of pertussis:

� azithromycin 10 mg/kg once daily for 1 dayand then 5 mg/kg once daily for 4 days

� clarithromycin 15 mg/kg twice daily in adivided dose for 7 days

� erythromycin 40 mg/kg three times daily in adivided dose for 7 days

– choice based on cost, side effects, etc.

34. Antibiotics should be administered as soon aspossible after onset of illness; there is no limit tothe start date for treatment of symptomatic,untreated cases of pertussis whose culture orPCR results are positive.

35. Patients should no longer be consideredinfectious after 5 days of therapy.

36. Infants < 2 months of age who are receivingmacrolide antibiotics should be monitored forsymptoms and signs of pyloric stenosis.

Chemoprophylaxis

37. For confirmed cases (culture, PCR, serology orepidemiologic link) or clinically diagnosed casesoccurring during an outbreak, chemoprophylaxisshould be given to the following:

� household contacts (including attendees atfamily day care centres) where there is avulnerable person (an infant < 1 year of age[vaccinated or not] or a pregnant woman inthe third trimester)

� for out of household exposures, vulnerableindividuals who have had face-to-faceexposure and/or have shared confined air for> 1 hour

38. For chemoprophylaxis, the same antimicrobialsand schedule should be used as outlined underTreatment.

39. When used, chemoprophylaxis should beimplemented as soon as possible.

� Efficacy is related to early implementationand is unlikely to be of any benefit after 21days have elapsed since the first contact.

40. Antibiotics recommended for the control ofpertussis where household chemoprophylaxis isindicated (index cases, household contacts)should be supplied by public health.

Notification and Early Treatment

41. There should be notification (see Appendix 1 fornotification procedures) of other contacts ofconfirmed cases in the following settings:

� other households

� non-family day care centres

� schools

� health care settings

� work places

42. Treatment should be based on symptomssuggestive of early pertussis (coryzal stage).

43. The same antibiotics and schedule should beused as outlined under Treatment.

44. The settings listed in recommendation 41 shouldbe assessed for special circumstances that mightwarrant chemoprophylaxis.

Outbreak Management

45. If there is a confirmed case in a household thefollowing apply:

� vaccination is not recommended foroutbreak management, but the opportunityshould be taken to update the immunizationstatus of contacts if required.

� exclusion is not a proven effective strategy;however, in high risk situations (where thereare vulnerable individuals – for instance,infants) exclusion until 5 days after the startof antibiotic therapy or, if no treatment is


given, until after 21 days and with negativeresults from culture or PCR should be at thediscretion of the medical officer of health.

46. If there are two or more confirmed casesepidemiologically linked in a non-householdsetting (school, day care centre without infants <1 year old) the following apply:

� Chemoprophylaxis is not indicated.

– In household-like settings use individualjudgement.

– Alert parents to signs and symptoms ofpertussis so that early diagnosis andtreatment can be initiated when needed;inform community physicians of increasedpertussis activity.

� Use the opportunity to update routinelyscheduled immunizations in school or daycare contacts as required.

– Catch up immunization of other cohortscan be considered by public healthauthorities.

– All parents of contacts should be notifiedof the possibility of purchasing vaccinefrom the family physician.

� Exclusion criteria are the same as inrecommendation 45.

47. Public health nurses should obtain training andgain expertise in taking nasopharyngeal swabs.

Research Agenda

Topics to be included on the research agenda are asfollows.

� Evaluation of each change recommended by thisconsensus conference upon implementation.

� Assessment of the population effectiveness ofsuch strategies as immunization of new mothers,immunization of household contacts of anewborn, immunization of other close contactsof a newborn.

� Methods to reduce mortality and morbidity(hospitalization) in young infants.

� Use of acellular pertussis vaccine in outbreakcontrol.

� Schedule issues– 5th dose– primary series– accelerated schedules– newborn immunization

� Efficacy of vaccine in adolescents (and adults)– This should not delay implementation.

� Seroepidemiology in new Canadian adolescents.

� Evaluation of single dose of azithromycin.

� Monitoring of macrolide resistance.

� Duration of protection of children fullyimmunized with acellular vaccine.

� Cost-effectiveness of different strategies.

� Investigation of the point at which patientsreceiving treatment are no longer infectious.

� Source of infection of young infants.

� Mechanisms of transmission related to– culture/PCR positive results– symptoms

� Effect of maternal immunization on infantdisease.

� Immunization during pregnancy.

� Role of maternal antibody (transplacental and viabreast milk) in the protection of infants in thefirst few months of life.

� The effect of the interval between boosterimmunization and childbirth on the productionof antibody titres that do or do not protectinfants.


REFERENCES

1. CDC. Pertussis – United States, 1997-2000. MMWR2002;51:73-6.

2. Wortis N, Strebel PM, Wharton M et al. B. pertussisdeaths: report of 23 cases in the United States, 1992and 1993. Pediatrics 1996;97:607-12.

3. Heininger U, Stehr K, Schmidt-Schläpfer G et al.infections and sudden unexpected

deaths in children. Eur J Pediatr 1996;155:551-53.

4. Jenkinson D. Natural course of 500 consecutive casesof whooping cough: a general practice population. BrMed J 1995;310:299-302.

5. Jenkinson D. Duration of effectiveness of pertussisvaccine: evidence from a 10-year community study.Br Med J 1988;296:612-14.

6. Yih WK, Lett SM, des Vignes FN et al. The increasingincidence of pertussis in Massachusetts adolescents andadults, 1989-1998. J Infect Dis 2000;182:1409-16.

7. Heininger U, Schmidt-Schläpfer G, Cherry JD et al.Clinical validation of a polymerase chain reactionassay for the diagnosis of pertussis by comparison withserology, culture, and symptoms during a large pertus-sis vaccine efficacy trial. Pediatrics 2000;105:e31.

8. Senzilet LD, Halperin SA, Spika JS et al and the Sen-tinel Health Unit Surveillance System PertussisWorking Group. Pertussis is a frequent cause of pro-longed cough illness in adults and adolescents. ClinInfect Dis 2001;32:1691-97.

9. Decker MD, Edwards KM. The multicenter acellularpertussis trial: an overview. J Infect Dis 1996; 174(suppl 3): 5270-5.

10. Grimprel E, Guiso N, Bégué P. New aspects of pertus-sis in France, 26 years after generalized pertussis vac-cination. Biologicals 1993;21:5-6.

11. Baron S, Njamkep E, Grimprel E et al. Epidemiologyof pertussis in France, 1993-1994. Pediatr Infect Dis J1997;17:412-18.

12. Gilbert S, Njamkepo E, Parent du Châtelet I et al.Evidence of pertussis with persistent coughin a French area with very high whole-cell vaccine cov-erage. J Infect Dis 2002.186 (in press).

13. Miller E, Fleming DM, Ashworth LAE et al.Serological evidence of pertussis in patients presentingwith cough in general practice in Birmingham.Commun Dis Public Health 2000;3:132-4.

14. Crowcroft NS, Spicer L, Tzivra O et al. Pertussis isunder-estimated in infants admitted to paediatric inten-sive care units and wards in London (abstract). Pro-ceedings of the 19th Annual Meeting of the EuropeanSociety for Paediatric Infectious Diseases, Istanbul,Turkey, 2001.

15. Morris A, McIntyre P, Elliot E et al. Hospitalised per-tussis in Australian infants in 2001(abstract). RoyalAustralian College of Physicians Annual ScientificMeeting, Brisbane, Australia, May 2002.

16. Thomas P, McInytre P, Jalaludin B. Survey of pertus-sis morbidity in adults in western Sydney. Med J Aust2000;173:74-76.

17. Poynton M, Irwig L, Hanlon M et al. Serologicaldiagnosis of pertussis: evaluation of IgA against wholecell and specific antigens asmarkers of recent infection. Epidemiol Infect 2002 (inpress).

18. Zepp F, Knuf M, Habermehl P et al. Pertussis-specificcell-mediated immunity in infants after vaccinationwith a tricomponent acellular pertussis vaccine. InfectImmun 1996;64:4078-84

19. Zepp F, Knuf M, Habermehl P et al. Cell-mediatedimmunity after pertussis vaccination and after naturalinfection. Dev Biol Stand 1997;89:307-14.

20. Tinnion, ON, Hanlon M. Acellular vaccines for pre-venting whooping cough in children. Cochrane Data-base Syst Rev 2000;(2):CD001478.

21. Taranger J, Trollfors B, Bergfors E et al. Immunologicand epidemiologic experience of vaccination with amonocomponent pertussis toxoid vaccine. Pediatrics2001;108 . URL: <http://www.pediatics.org/cgi/content/full/108/6/e115>

22. Salmaso S, Mastrantonio P, Tozzi AE et al. Sustainedefficacy during first 6 years of life of 3-componentacellular pertussis vaccines administered in infancy: theItalian experience. Pediatrics 2001;108(5):e81.

23. Lugauer S, Heininger, U, Cherry JD et al. Long-termclinical effectiveness of an acellular pertussis compo-nent vaccine and a whole cell component vaccine. Eur JPediatr 2002;161:142-6.

24. Halperin SA, Eastwood BJ, Barreto L et al. Adversereactions and antibody response to four doses ofacellular or whole cell pertussis vaccine combined withdiphtheria and tetanus toxoids in the first 19 months oflife. Vaccine 1996;14:767-72.


http://www.pediatics.org/cgi/content/full/108/6/e115

http://www.pediatics.org/cgi/content/full/108/6/e115

25. Halperin S, Scheifele D, Barreto L et al. Comparisonof a fifth dose of a five-component acellular or a wholecell pertussis vaccine in children four to six years ofage. Pediatr Infect Dis J 1999;18:772-79.

26. Pichichero ME, Edwards KM, Anderson EL et al.Safety and immunogenicity of six acellular pertussisvaccines and one whole-cell pertussis vaccine given as afifth dose in four- to six-year old children. Pediatrics2000;105:e11.

27. Schmitt HJ, Beutel K, Schuind A. Reactogenicity andimmunogenicity of a booster dose of a combined diph-theria, tetanus, and tricomponent acellular pertussisvaccine at 14 to 28 months of age. J Pediatr1997;130:616-23.

28. Halperin SA, Smith B, Russell M et al. An adult for-mulation of a five-component acellular pertussis vac-cine combined with diphtheria and tetanus toxoids issafe and immunogenic in adolescents and adults. Vac-cine 2000;18:1312-19.

29. Hemels MEH et al. Economic evaluation of anextended acellular pertussis programme for adolescentsin Ontario, Canada. Submitted for publication.

30. National Advisory Committee on Immunization,Advisory Committee on Epidemiology, CanadianPaediatric Society. Statement on management of per-sons exposed to pertussis and pertussis outbreak con-trol. CCDR 1994;20(22):193-200.

31. National Advisory Committee on Immunization.Canadian immunization guide, 4th ed. Ottawa: Cana-dian Medical Association, 1998.

32. Halperin S, Bortolussi R, Langley JM et al. Seven daysof erythromycin is as effective as fourteen days for thetreatment of infections. Pediatrics1997;100:65-71.

33. Lebel MH, Mehra S. Efficacy and safety ofclarithromycin versus erythromycin for the treatmentof pertussis: a prospective, randomized, single blindtrial. Pediatr Infect Dis J 2001;20:1149-54.

34. Halperin S, Bortolussi R, Langley JM et al. A random-ized, placebo-controlled trial of erythromycin estolatechemoprophylaxis for household contacts of childrenwith culture-positive infection.Pediatrics 1999;104 URL:<http://www.pediatics.org/cgi/conent/full/104/4/e42>

35. De Serres G, Boulianne N, Duval B. Field effectivenessof erythromycin prophylaxis to prevent pertussis withinfamilies. Pediatr Infect Dis J 1995;14:969-75.

36. Deeks S, De Serres G, Boulianne N et al. Failure ofphysicians to consider the diagnosis of pertussis in chil-dren. Clin Infect Dis 1999;28:840-46.


http://www.pediatics.org/cgi/conent/full/104/4/e42

APPENDIX 1

Notification and Early Treatment of Contacts(See Recommendation 41)

� The notification of individuals exposed toconfirmed cases of pertussis in the settingscovered by Recommendation 41 should comprise– notification that a case of pertussis has been

diagnosed in the setting– a brief description of the case of pertussis, its

symptoms, incubation period and period ofcommunicability

– advice to seek medical attention if symptomsdevelop

– the request to notify public health.

� To this notification should be attached a letter tothe physician, which should provide informationon pertussis and its diagnosis, andrecommendations for– physician assessment– nasopharyngeal swab for pertussis, and other

diagnostic modalities– early treatment, listing the recommended

antibiotics and their schedules– notification of public health.


APPENDIX 2

List of Participants

Ms. Mary AppletonSenior ManagerCanadian Immunization Awareness ProgramCanadian Public Health Association400-1565 Carling AvenueOttawa, ON, K1Z 8R1

Dr Horacio ArrudaDirecteur de la ProtectionMSSS1075, chemin Ste-Foy, 2e étageQuébec, QC,G1S 2M1

Dr. Charles BadenhorstDepartment of Health235 Townsend StreetSydney, NS, B1P 5E7

Dr. Christopher BalramProvincial Epidemiologist & DirectorProvincial Epidemiology ServicePO Box 5100Carleton PlaceFredericton, NB, E3B 5G8

Dr. Luis BarretoVice President, Public AffairsDirector, CPP-IPHAAventis Pasteur1755 Steeles Ave WestToronto, ON, M2R 3T4

Ms. Loretta BartlettPublic Health Nurse ManagerHealth & Social Services, NUPo Box 1003Rankin Inlet, NU, X0C 0G0

Ms. Mary BashaCommunicable Disease Control CoordinatorHealth & Community Services, St. John’s Region20 CordageBox 13122, Stn ASt. John’s, NF, A1B 4A4

Ms. Julia BenyakManager, Projects & PlanningPublic Health BranchMinistry of Health & Long -Term Care8/F 5700 Yonge St.North York, ON, M2M 4K5

Ms. Nancy BlackmoreCommunicable Disease Prevention & ControlCoordinatorPublic Health Services60 Vancouver StreetYarmouth, NS, B5A 2P5

Dr. Monica BologaDirector, Clinical DevelopmentAventis Pasteur1755 Steeles Ave WestNorth York, ON, M2R 3T4

Mr. Andrew BostonSenior Product ManagerAventis Pasteur1755 Steeles Ave WNorth York. ON, M2R 3T4

Dr. Ian BowmerDean, Faculty of MedicineMemorial University of Newfoundland300 Prince Philip Drive, HSCSt. John’s, NF, A1B 3V6


Ms. Lynn CochraneProject ManagerHealth & Wellness (Public Health)520 King Street, 2nd FloorFredericton, NB, E3B 5G8

Dr. Natasha CrowcroftConsultant EpidemiologistImmunisation DivisionPHLS CDSC61 Colindale AvenueLondon, NW9 5EQUK

Dr. Nancy CulletonMedical Officer of HealthHealth & Community Services - Central143 Bennett DriveGander, NF, A1V 2E6

Dr. Colin D’CunhaChief Medical Officer of HealthMinistry of Health & Long-Term Care8/F 5700 Yonge St.North York, ON, M2M 4K5

Dr. Patricia DalyMedical Health OfficerVancouver Coastal Health Authority#800-601 West BroadwayVancouver, BC, V5Z 4C2

Dr Gaston De SerresMédecin épidémiologisteInstitut national de santé publique du Québec2400, rue d’EstimauvilleBeauport, QC, G1E 7G9

Dr Philippe De WalsDépartment des sciences de la santé communautaireUniversité de Sherbrooke3001, 12e Avenue NordSherbrooke, QC, J1H 5N4

Dr Bernard DuvalGroupe scientifique en immunisationInstitut national de santé publique du Québec2400 D’EstimauvilleBeauport, QC, G1E 7G9

Dr. Kathryn EdwardsProfessor of PediatricsDepartment of PediatricsVanderbilt University Medical Center1161 21st Avenue SouthRoom D-7226, Medical Center NoNashville, TN, 27232-2581, USA

Dr. Joanne EmbreeHead, Department of Medical MicrobiologyUniversity of Manitoba5th Floor730 William AvenueWinnipeg, MB, R3E 0W3

Dr. Ross FindlaterDeputy Medical Health OfficerRegina Health District2110 Hamilton StreetRegina, SK, S4P 2E3

Dr. Eleni GalanisField EpidemiologistDivision of ImmunizationHealth CanadaTunney’s PasturePL0603E1Ottawa, ON, K1A 0L2

Dr. Ian GemmillMedical Officer of HealthKingston, Frontenac & Lennox & Addington HealthUnit221 Portsmouth AvenueKingston, ON, K7M 1V5

Dr. Swee Han GohSenior ScientistBC Centre for Disease Control655 W 12th AvenueVancouver, BC, V5Z 4R4

Dr. Karen GrimsrudActing Provincial Health OfficerAlberta Health and Wellness23rd Floor10025 Jasper AvenueEdmonton, AB, T5J 2N3


Dr. Nicole GuisoHead of the Bordetella UnitDirector, National Reference Centre for BordetellaInstitut Pasteur25, rue du Dr. RouxParis Cedex 15, 75724France

Dr. Scott HalperinProfessor of PediatricsAssociate Professor of Microbilogy & ImmunologyIWK Health Centre5850 University AvenueHalifax, NS, B3T 3G9

Mrs. Beth HalperinRN MN (Center Manager)Clinical Trials Research Center1WK Health Centre5850 University AveHalifax, NS, B2T 1J6

Ms. Laurette HamiltonManager of Community Health ServicesHay River Community Health Services3 Gaetz DriveHay River, NT, X0E 0R8

Dr. Frances JamiesonMedical MicrobiologistOntario Ministry of Health & CACMID81 Resources RoadToronto, ON, M9P 3T1

Dr. Marcia JohnsonDeputy Medical Officer of HealthCapital Health Authority, AB300, 10216-124 StreetEdmonton, AB, T5N 4A3

Dr. Barbara KawaSenior Medical ConsultantPublic Health BranchMinistry of Health & Long-Term Care8/F 5700 Yonge StreetNorth York, ON, M2M 4K5

Ms. Diane KickhamPublic Health NurseEastern Kings Health RegionPo Box 640Souris, PE, C0A 2B0

Dr. Arlene KingChief, Division of Immunization and RespiratoryDiseasesCentre for Infectious Disease Prevention & ControlHealth CanadaTunney’s Pasture, AL 0300DOttawa, ON, K1A 0L2

Mr. Craig LaferriereTherapy Area LeaderClinical DepartmentGlaxoSmithKline7333 Mississauga Road NorthMississauga, ON, L5N 6L4

Dr. Joanne LangleyAssociate Professor of PediatricsIWK Health Centre5850 University AvenueHalifax, NS, B3J 3G9

Dr. Bryce LarkeChief Medical Health OfficerYukon Health and Social Services#4, Hospital RoadWhitehorse, YK, Y1A 3H8

Ms. Maureen LaurieManagerCommunicable Disease Control & Vaccine ProgramsPopulation Health3475 Albert StreetSaskatoon, SK, S4S 6X6

Dr. Pierre LavigneDirector, Medical Affairs CanadaAventis Pasteur1755 Steeles Aveune WestNorth York, ON, M2R 3T9

30 National Consensus Cionference on Pertussis

Dr. Eric Le FevreUK General PractitionerLakeside Health CentreThamesmeadLondon, SE2 9UQUK

Dr. Grace LeeFellow in Infectious DiseasesChildren’s Hospital Boston300 Longwood AveBoston, MA, 2115USA

Dr. Vittorio LentiniCommunicable Disease ControlDepartment of National Defence1745 Alta Vista DriveRoom 364BOttawa, ON, K1A 0K6

Dr. Judy MacDonaldDirector, Health ProtectionDeputy Medical Officer of HealthCalgary Health Region, Health ProtectionBox 4016, Station CCalgary, AB, T2T 5T1

Dr. Victor MarchessaultProfessorPediatrics and Infectious DiseasesChildren’s Hospital of Eastern Ontario1382 Gerald St.Cumberland, ON, K4A 3N2

Dr. Allison McGeerMicrobiologistMount Sinai Hospital650 University AveToronto, ON, M5G 1X5

Dr. Peter McIntyreDeputy DirectorNCIRSChildren’s Hospital at WestmeadUniversity of SydneyLocked Bag 4001Westmead, NSW 2145Australia

Dr. Jussi MertsolaProfessor of PediatricsDepartment of PediatricsTurku University HospitalKiinamyllynkatu 4-8PL 52Turku, 20521Finland

Dr. Christina MillsCPHA PresidentHallman Visiting ProfessorCentre for Behavioural Research & ProgramEvaluationUniversity of Waterloo11 Huron Avenue NorthOttawa, ON, K1Y 0W1

Dr. Trudy MurphyNational Immunization ProgramCenters for Disease Control & Prevention1600 Clifton Road NEMS E-61Atlanta, GA, 30333USA

Dr. Seema NagpalAssociate Director, EpidemiologyOffice for Public HealthCanadian Medical Association1867 Alta Vista DriveOttawa, ON, K1G 3Y6

Ms. Anne NeatbyCommunicable Disease NurseOffice of Medical Officer of HealthHealth and Social ServicesBox 2000Charlottetown, PE, C1A 7N8

Ms. Cathy O’KeefeDisease Control Nurse SpecialistDepartment of Health & Community ServicesPO Box 8700Confederation BuildingSt. John’s, NF, A1B 4J6

National Consensus Cionference on Pertussis 31

Dr. Patrick OlinProfessor of PediatricsSwedish Institute for Infectious Disease ControlStockholm, SE 171 82Sweden

Dr. Geraldine OsborneAssistant CMOHDepartment of Health & Social ServicesPo Box 1000, Station 1000Iqaluit, NU, X0A 0H0

Dr. Laszlo PalkonyayManager, Vaccines DivisionBiologics and RadiopharmaceuticalsEvaluation CentreHealth CanadaBuilding 6, AL 0606CZTunney’s PastureOttawa, ON, K1A 0L2

Prof. Ross PennieProfessorMcMaster University2N30-1200 Main Street. WestHamilton, ON, L8N 3Z5

Dr. Mark PepplerAssociate ProfessorDept. of Medical Microbiology & ImmunologyUniversity of AlbertaEdmonton, AB, T6G 2H7

Ms. Karen PielakNurse EpidemiologistEpidemiology ServicesBC Centre for Disease Control655 West 12th AvenueVancouver, BC, V5Z 4R4

Dr. Babak PourbohloulDirector, Division of Mathematical ModelingEpidemiology ServicesUBC Centre for Disease Control655-12th Ave WestVancouver, BC, V5Z 4R4

Dr. Sam RatnamDirectorNF Public Health Laboratory100 Forest RdPO Box 8800St. John’s, NF, A1B 3T2

Dr. Susan RichardsonDirector, MicrobiologyHospital for Sick Children555 University AveToronto, ON, M5G 1X8

Dr. Lode SchuermanAssociate Director, Clinical DevelopmentGlaxoSmithKline Biologicalsrue de l’institut, 89Rixensart, B-1330Belgium

Ms. Perica SeverProfessional Comm. ManagerHIV, Oncology, VaccinesGlaxoSmithKline Inc.7333 Mississauga Road NorthMississauga, ON, L5N 6L4

Dr. Danuta SkowronskiPhysician EpidemiologistEpidemiology ServicesBC Centre for Disease Control655-12th Avenue WestVancouver, BC, V5Z 4R4

Ms. Lorna StorbakkenDirectorMinistry of Health Planning, BC2nd Floor, 1520 Blanshard StreetVictoria, BC, V8W 3C8

Dr. Ben TanRoyal University HospitalRM 3729103 Hospital DriveSaskatoon, SK, S7N 0W8

32 National Consensus Cionference on Pertussis

Dr. Raymond TsangHead, Vaccine Preventable Bacterial DiseasesNational Microbiology Laboratory1015 Arlington StreetWinnipeg, MB, R3E 3R2

Dr. Paul VarugheseHead, Surveillance & Technical SupportDivision of ImmunizationHealth CanadaTunney’s PastureAL 0603E1Ottawa, ON, K1A 0L2

Dr. Joel WardProfessor of PediatricsDepartment of PediatricsHarbor UCLA Medical Center1124 W. Carson St. E-6Torrance, CA, 90502USA

Ms. Wanda WhiteCommunicable Disease ConsultantHealth & Social Services, Gov’t of the NWTBox 1320, CST-6Yellowknife, NT, X1A 2L9

Mr. Brian WigleManagerTenders, Key AccountsGlaxoSmithKline2505 Meadowvale BlvdMississauga, ON, L5N 2R7

Dr. Fred ZeppUniversity ProfessorKinderklinik und KinderpoliklinikJohannes Gutenberg UniversitatLangenbeckstrasse 1Mainz, D-55131Germany

National Consensus Cionference on Pertussis 33

Documents

Our missionis tohelpthe people ofCanada maintainandimprove their health. · ending in an inspiratory whoop and vomiting. The disease can lead to serious complications in young infants,