THE JOURNAL OF THE CANADIAN PAEDIATRIC SOCIETY

FEATURE ISSUES

Vaccine-preventable Diseases Update

UPDATE ON THE EPIDEMIOLOGY OF SELECTED VACCINE-PREVENTABLE DISEASES

This section continues on the theme of previous national reports and provides an update on selected vaccine preventable diseases (1). The data are preliminary, but it is noteworthy that 1998 registered the lowest number of cases ever reported for Hib, measles, mumps and rubella (Table 1).

TABLE 1: Reported cases of selected vaccine-preventable diseases, Canada, 1994 to 1998
	1994*		1995*		1996*		1997†		1998†
Disease	Cases	Rates‡	Cases	Rates‡	Cases	Rates‡	Cases	Rates‡	Cases	Rates‡
Diphtheria	1	–	2	–	0	–	1	–	0	–
Haemophilus influenzae type b	57	0.2	52	0.2	55	0.2	60	0.2	50	0.2
Hepatitis B	3079	11.2	3005	10.1	2385	8.0	1591	5.3	1702	5.6
Measles	523	1.9	2361	8.0	332	1.1	581§	1.9	12§	0.04
Mumps	369	1.4	402	1.4	313	1.0	264	0.9	110	0.4
Pertussis	10,151	37.0	9818	33.2	5408	18.0	4439	14.8	7519	25.1
Poliomyelitis	0	–	1¶	–	0	–	0	–	0	–
Rubella	237	0.9	300	1.0	302	1.0	4007**	13.2	67	0.2
Rubella, congenital††	4	1.0	2	0.5	2	0.5	1	0.3	1	0.3
Tetanus	3	–	6	–	3	–	3	–	2	–
*Based on cases reported to the national Notifiable Disease Registry System (NDRS), Division of Disease Surveillance, Laboratory Centre for Disease Control; †1997 and 1998 data are provisional; ‡Unless otherwise stated, rates are calculated per 100,000 population and rounded off to the first decimal place; §Based on cases reported to the Enhanced Measles Surveillance System; ¶Vaccine associated paralytic poliomyelitis in a contact of a vaccinee; **Approximately 98% of rubella cases reported in 1997 were reported from Manitoba where an outbreak of rubella occurred, starting October 1996 through December 1997; ††Based on cases reported to the Canadian Paediatric Surveillance Program/the Immunization Monitoring Program ACTive Network/NDRS. Recorded by date of  birth. Rates are calculated per 100,000 births

Hepatitis B

The 1998 crude incidence of 5.6/100,000 population for hepatitis B varied little from the 5.3/100,000 seen in 1997, but does continue to decline over time (Figure 1). The 1998 age-specific incidence remains highest among 25- to 29-year olds at 9.4/100,000 (207 cases) followed by  20- to 24-year olds at 8.3/100,000 (169 cases) and 30- to 39-year olds at 8.2/100,000 (430 cases). More cases continue to be diagnosed in males than females at a ratio of 5:2.

Figure 1) Crude incidence of hepatitis B reported in Canada, 1986 to 1998

Invasive Hib

Since national reporting began for invasive Hib in 1986, the annual number of cases ranged from 100 to 650/annum. After 1993, when the infant conjugate vaccines were introduced into all routine immunization schedules, the number of cases decreased to less than 60 cases/year (Figure 2). The lowest recorded number was reported in 1998, with only 50 cases. In 1998, the highest incidence remained in the younger than one-year-old age group with 1.9/100,000 (seven cases). The next highest age-specific incidence was in the one- to four-year-old age group at 0.6/100,000 (10 cases).

Figure 2) Number of reported invasive Haemophilus influenzae type b cases in Canada, 1986 to 1998. PRP Polyribose ribitol phosphate; PRP-D PRP-Diphtheria toxoid conjugate

Mumps

The reported incidence for mumps in 1998 was the lowest on record (Figure 3). One hundred and 10 cases  were registered, a rate of 0.4/100,000. The highest age-specific incidence continued to occur in the five- to nine- year-old age group at 1.9/100,000 (38 cases), followed by the 10- to 14-year-old age group at 0.8/100,000 (17 cases) and the one- to four-year-old age group at 0.8/100,000 (12 cases). The male to female ratio was 3:2.

Figure 3) Crude incidence of mumps reported in Canada, 1924 to 1998. No national reporting between 1959 and 1985

Rubella

In 1998, rubella incidence fell to the lowest number ever recorded nationally at 0.2/100,000 or 67 cases (Figure 4). The majority of cases were diagnosed in the 15- to 19-year-old age group. The highest age-specific incidence was in the younger than one-year-old age group at 2.2/100,000 (eight cases) followed by the one- to four-year-old age group at 0.8/100,000 (13 cases). The male to female ratio was 1:2.

Figure 4) Crude incidence of rubella reported in Canada, 1924 to 1998. No national reporting between 1959 and 1968

Pertussis

The cyclical increase in pertussis rates, which began in the late 1980s, continued in 1998 with 7519 reported pertussis cases, an incidence of 25.1/100,000 (Figure 5). The highest age-specific incidence occurred in the younger than one-year-old age group at 166.9/100,000 (606 cases), followed by 127.3/100,000 (2608 cases) in the five- to nine-year olds and 100.2/100,000 (1556 cases) in the one- to four-year-old age group. The cases are distributed almost equally between the sexes.

Figure 5) Crude incidence of pertussis reported in Canada, 1924 to 1998

Pertussis remains the least controlled vaccine-preventable disease for which routine childhood immunization is available. Contributing factors to this include a reluctance to seek vaccination and the suboptimal protection offered by the whole cell vaccine. New and improved acellular vaccines were licensed in Canada in 1996, and adopted by all provincial and territorial vaccine programs by mid-1998. Close monitoring will help assess the effectiveness of this new vaccine in decreasing the incidence of pertussis over time.

Revised case definitions for diseases under national surveillance will be published as a supplement to the Canada Communicable Diseases Report in the fall of 1999. For more information, contact the Division of Disease Surveillance, Bureau of Infectious Diseases, Health Canada, telephone 613-946-2328.

REPORTS ON RARE DISEASES

Tetanus

Three cases of tetanus were reported in 1997 and two in 1998.

In 1997, two clinical cases and one laboratory confirmed case were reported from Ontario, Nova Scotia and Alberta, respectively. The first clinical case was a 50-year-old male who injured his foot stepping on bamboo. He recalled vaccination as a youth, but was unable to specify a date. The second clinical case was in an 80-year-old male from Nova Scotia. He was cutting alders and poked himself in the leg with part of the tree. His vaccination status is unknown. The laboratory-confirmed case was a 10-year-old boy with a history of stepping on a nail eight days before admission to hospital. He had a history of three doses of diptheria, pertussis and tetanus (DPT) vaccine as an infant (two, five and nine months of age). Vaccination was discontinued after the third dose due to adverse reaction consisting of fever and generalized rash.

Two tetanus cases were reported in Ontario in 1998. One was clinically diagnosed in a 37-year-old male lumberjack wounded on the job. The other was laboratory-confirmed in a 67-year-old male farmer who cut his leg on a sharp board. Prior vaccine receipt was unknown for both of these cases.

All cases recovered following treatment.

Diphtheria

One probable diphtheria case was reported in the Yukon in 1997. The case was a 64-year-old male who developed swelling and redness in the left tonsillar region, with a greyish-white membrane on the left lateral tonsil that extended up onto the soft palate. The patient received diphtheria antitoxin and eventually recovered. He had received a diphtheria and tetanus toxoid (Td adult type) vaccination approximately four years earlier.

ACTIVE SURVEILLANCE OF SELECTED VACCINE PREVENTABLE DISEASES

Since the early 1980s, all provinces and territories have reported aggregate data on a monthly basis to the national Notifiable Diseases Registry System (NDRS) at Health Canada. Since 1990, Alberta, British Columbia, Ontario, Quebec and Saskatchewan (representing 88% of the Canadian population) have been submitting case by case reports on a continuing basis to the NDRS. (Other provinces or territories have submitted case by case data but on an intermittent basis.). Unfortunately, the data elements in case by case reporting vary according to jurisdiction, and there is often a significant time delay in the transfer of records.

In recent years, one effort to improve the completeness and timeliness of reporting for specific vaccine preventable diseases has been through active surveillance. Three diseases currently under active surveillance at the national level are polio (through surveillance of acute flaccid paralysis [AFP]), congenital rubella syndrome (CRS) and measles.

SURVEILLANCE SYSTEMS

Since 1991, the Immunization Monitoring Program ACTive (IMPACT) Network of 11 paediatric care centres (representing approximately 85% of tertiary care paediatric beds in Canada) has been conducting active case finding on childhood vaccine-preventable diseases. Nurse monitors at each IMPACT site review laboratory reports, admission and discharge records to identify cases, and complete detailed case report forms.

In January 1996, the Canadian Paediatric Surveillance Program (CPSP) was initiated to look for rare childhood conditions, including CRS and AFP (1). Approximately 2000 paediatricians are asked to complete monthy report forms regardless of whether they see a case or not. Paediatricians who do report cases are asked to submit detailed report forms. Provincial and territorial public health authorities are consulted to determine whether cases have been previously reported. The overall response rate for the CPSP has increased from 76% in 1996 to 82% in 1997 and 86% in 1998 (2,3).

In July 1996, the Rubella-Associated Adverse Pregnancy Outcomes surveillance system (RAAPO) was piloted by the Division of Immunization, Health Canada. The objective of RAAPO is to estimate the magnitude of all adverse outcomes as a result of rubella during pregnancy, including still births, spontaneous abortions, and therapeutic abortions. Participating laboratories identify women 15 to 45 years of age with positive rubella-specific immunoglobulin (RIgM) and forward the results to regional public health authorities. Public health officials gather information on identified women, including demographic data, pregnancy status and immunization histories. All pregnant women are followed to determine outcomes. Of 22 laboratories performing RIgM testing in Canada, 21 (performing  more than 95% of testing in Canada) agreed to participate.

The Enhanced Measles Surveillance System was modified in 1998 to an e-mail based reporting system. Every week, when prompted, the provinces and territories reply via e-mail to Health Canada. If there are no cases then the provinces and territories reply with no comment. If there is a case, a case report is completed and attached. The weekly response rates for 11 regions averaged around 83% from the systems implementation February 7, 1998 to December 31, 1998 (one region reported cases only). Variables collected include demographic data, vaccine history and exposure history.

REFERENCES

1. Sockett PN. Canadian Paediatric Surveillance Program: Two years of a system for investigating unusual paediatric disorders. Paediatr Child Health 1998;3:240-5.

2. Canadian Paediatric Surveillance Program, 1996 Report. Ottawa: Canadian Paediatric Society, 1997.

3. Canadian Paediatric Surveillance Program, 1997 Report. Ottawa: Canadian Paediatric Society, 1998.

Poliomyelitis

The surveillance of AFP in children younger than age 15 years is used to monitor potential cases of paralytic poliomyelitis. AFP surveillance was initiated in 1991 through active monitoring of admissions to paediatric tertiary care hospitals in IMPACT network. In 1996, surveillance was expanded to include paediatrician-based reporting through the CPSP. All AFP reports are reviewed and analyzed by LCDC, and cases compatible with suspected paralytic poliomyelitis are referred to the national Working Group on Polio Eradication (WGPE) for further review to rule out poliomyelitis.

Table 2 shows the reporting rate and age distribution of AFP cases from 1993 to 1998. In the period following certification of polio eradication, from 1995 to 1998, the average number of AFP cases in patients younger than 15 years of age reported annually was 36 (ranging from 30 to 42 cases), which represents an average rate of 0.6/100,000 population younger than 15 years of age (ranging from 0.5 to 0.7/100,000). The AFP reporting rate in Canada remains below the World Health Organization estimated background rate of 1/100,000 population younger than 15 years of age in the absence of wild poliovirus transmission (1). However, the AFP rate in Canada has increased since the introduction of paediatrician-based reporting through the CPSP, up to 0.7/100,000 population in 1998. The current CPSP reporting network enhances the completeness of AFP surveillance by ensuring that, in addition to cases admitted to paediatric tertiary care hospitals, cases seen at other hospitals or community clinics are also reported. In addition, reporting paediatricians submit both negative reports (no cases seen) and reports of AFP cases seen.

On an average, the final neurological diagnosis in reported AFP cases is Guillain-Barré syndrome in 75% of cases, transverse myelitis in 13% of cases and a variety of other paralytic illnesses in the remaining 13% of cases (Table 3). An ongoing challenge has been the need to ensure that adequate stool investigations are carried out for all AFP cases. Overall, approximately one-third of AFP case reports include a report of a timely stool investigation for the isolation of polioviruses or other enteroviruses, whereas the remainder report no adequate stool investigation or have no information. On the other hand, more than 80% of cases have had a neurological investigation (including one or more of nerve conduction studies, electromyography, magnetic resonance imaging or computed tomography scan) to support the final neurological diagnosis. In 1997, the WGPE published a protocol for the investigation of suspected cases of paralytic poliomyelitis and AFP cases. The protocol emphasizes that the single most important laboratory investigation for the diagnosis of paralytic poliomyelitis is a stool specimen collected within two weeks of onset of paralysis for the isolation of wild or vaccine strain poliovirus (2). In addition, regular reminders are issued to paediatricians and IMPACT reporters about the importance of stool investigations in all AFP cases.

REFERENCES

1. de Quadros CA, Hersh BS, Olivé JM, Andrus JK, da Silveira CM, Carrasco PA. Eradication of wild poliovirus from the Americas: acute flaccid paralysis surveillance, 1988-1995. J Infect Dis 1997;175(Suppl 1):S37-42.

2. Working Group on Polio Eradication, Bentsi-Enchill A. Protocol for the investigation of acute flaccid paralysis and suspected paralytic poliomyelitis. Paediatr Child Health 1997;2:409-12.

Congenital rubella

Paediatrician-based active surveillance through the CPSP began in January 1996, and, since April 1996, cases reported to IMPACT have been forwarded to the CPSP. Paediatricians participating in CPSP are also asked to report infants with congenital rubella infection (CRI), defined as cases with no clinically compatible manifestations but with laboratory confirmation of infection. Given that the majority of infants infected with rubella in utero have no detectable clinical abnormalities at birth and many will go on to develop late-onset manifestations, it is important that CRI cases be identified.

Table 4 shows the number of CRS cases by year of reporting to surveillance systems in Canada from 1996 to 1998. Five older children previously diagnosed but not reported to NDRS were captured by active surveillance in 1996 and 1997. Of the newly diagnosed cases from 1996 to 1998, three were newborns and one was an adolescent with late-onset manifestations.

Table 5 shows the number of CRS cases by year of birth reported in Canada from 1996 to 1998. Since 1996, with enhanced surveillance through CPSP in place, only one to two reports of children born with CRS per year (0.3 to 0.5/100,000 births) have occurred.

Table 6 shows the CPSP data on the characteristics of the three cases born in Canada from 1996 to 1998. Two cases were infants of foreign-born mothers from countries where rubella immunization was not routine. Two cases were potentially preventable because the mothers were tested to be rubella-susceptible during a previous pregnancy but did not receive vaccination.

TABLE 4: Congenital rubella syndrome (CRS) by year of reporting to Canadian Paediatric Surveillance Program (CPSP)/the Immunization Monitoring Program ACTive (IMPACT) Network and Notifiable Diseases Registry System (NDRS), January 1996 to December 1998
	Number of CRS reported to CPSP/IMPACT			Total number of CRS reported to NDRS
Year of reporting	Newly diagnosed	Previously diagnosed but not reported	Total
1996	1	3	4	2
1997	2	2	4	1
1998	1	0	1	1
NDRS data for 1997 and 1998 are provisional

TABLE 5: Congenital rubella syndrome by year of birth reported to Canadian Paediatric Surveillance Program (CPSP)/the Immunization Monitoring Program ACTive (IMPACT) Network and Notifiable Diseases Registry System (NDRS), January 1996 to December 1998
	Reported to
Year of birth	NDRS only	CPSP/IMPACT only	NDRS and CPSP/IMPACT	Total
1996	1	0	1	2
1997	0	0	1	1
1998	0	0	1	1
NDRS data for 1997 and 1998 are provisional

TABLE 6: Characteristics of infants with congenital rubella syndrome born in Canada from 1996 to 1998
Year of birth	Laboratory-confirmed	Clinical manifestations	Mother born in Canada	Previous maternal rubella IgG screening test	Maternal rubella immunization
1996	Yes	Multiple	No	Positive	Unknown
1997	Yes	Multiple	No	Negative	No
1998	Yes	Multiple	Yes	Negative	No
Ig Immunoglobulin

So far, no CRI has been reported to CPSP. The degree of underdiagnosis and under-reporting for CRI, CRS with less severe manifestations and CRS with late-onset manifestations is unknown.

Between July 1, 1996 and June 30, 1998, 145 women aged 15 to 44 years with positive RIgM were reported by five (24%) of 21 laboratories participating in the Rubella-Associated Adverse Pregnancy Outcomes Surveillance System (RAAPO). Twenty-one (14.5%) of the eligible cases were pregnant at the time of RIgM testing, of which 19 were from Manitoba where a large outbreak of rubella occurred. Of 14 pregnant women with known immunization histories, eight (57%) had been immunized against rubella, of whom four had been vaccinated less than nine months before IgM testing. Of the 17 pregnant women who did not receive recent rubella vaccination, 11 (64%) had clinically ‘healthy’ newborns, and six (36%) had adverse pregnancy outcomes, including four induced abortions, one spontaneous abortion and one fetal death. RAAPO failed to capture three CRS cases identified by the other surveillance systems during the same surveillance period. Further evaluation of RAAPO, especially an assessment of under-reporting, is needed.

In summary, rubella infection in women of childbearing age continues to occur in Canada, but the number of newborns with CRS appears to be on a decline. There have been no reports of children with CRI to the CPSP or RAAPO. Based on the data from RAAPO, 36% of pregnant women with serologically confirmed rubella infection experienced fetal loss.

Measles

In 1997, Canada recorded 581 confirmed cases of measles. In 1998, that number decreased to 12, the lowest number ever recorded nationally in Canada. In 1998, all cases were reported to Health Canada through an e-mail based surveillance system. For a measles case to be considered confirmed at the national level, it has to satisfy the following case definition.

• Laboratory confirmation of infection in the absence of recent (1 to 14 days) immunization with measles containing vaccine (a laboratory-confirmed case does not have to meet the clinical illness description):
• isolation of measles virus from an appropriate clinical specimen
• or a significant rise in measles-specific antibody titre between acute and convalescent sera
• or a positive serological test for measles IgM using a recommended assay

OR

• clinical measles in a person who is epidemiologically linked to a laboratory-confirmed case, where a clinical case is characterized by all of the following features: fever 38.3°C or greater; cough, coryza or conjunctivitis; and generalized maculopapular rash for a least three days.

All 12 reported cases were confirmed in the laboratory by testing for measles-specific IgM antibodies and verified by the national Working Group on Measles Elimination in Canada (WGMEC). One specimen for measles virus isolation was collected and identified as MVi/Montreal.CAN/19.98 [D5]. The median age at onset of rash was five years (age range younger than one year to 33 years) with a 7:5 female to male ratio. Only two cases were known to require hospitalization.

Vaccine histories were available for nine of the 12 confirmed cases. Seven cases received the first vaccine and two had not. Of the two unvaccinated cases, one was not vaccinated because of a history of egg allergy (Egg allergy is no longer considered a contraindication to immunization with MMR. See Canadian Immunization Guide – 1998 [5th edition], page 122) and one had “missed” the appointment for immunization. for those vaccinated cases, two received the vaccine before the first birthday while living outside canada. Only one of nine received a second dose of measles, mumps and rubella (MMR) vaccine.

The cases were distributed across the country and, unlike the majority of cases in 1997 (1), were not related to outbreaks (Table 7).

TABLE 7: Confirmed measles cases reported to the Enhanced Measles Surveillance System
Province	1998*	1997
Newfoundland	0	9
Prince Edward Island	0	0
Nova Scotia	0	2
New Brunswick	0	4
Quebec	2	4
Ontario	7	22
Manitoba	0	0
Saskatchewan	1	20
Alberta	1	245
British Columbia	1	275
Yukon Territory	0	0
Northwest Territories	0	0
Total	12	581
*Preliminary data

Five of the confirmed measles cases in 1998 travelled outside Canada seven to 21 days before the onset of rash. Only one case had an identified contact with another measles case and that was in an individual who was exposed outside Canada.

One additional case is to be reviewed by WGMEC because it was laboratory confirmed by two separate laboratory tests, but not by the IgM capture assay currently used by Health Canada. Four additional reports were received on patients exhibiting clinical symptoms but without confirmatory laboratory work to support the diagnosis. Documentation on three of the four ‘clinical’ cases indicates that the caregiver refused and/or the clinician was unable or unwilling to collect a serum sample. No specimens for measles virus isolation were collected (2).

In summary, as the country moves towards the goal to eliminate indigenous measles, it is important to sustain and even improve current immunization coverage for all susceptible populations. As well, clinicians must be urged to maintain a high index of suspicion for measles, to report all suspect cases rapidly and to confirm all suspect cases. Most cases meeting the clinical case definition will NOT be measles because of the nonspecificity of the clinical definition; therefore, only cases with laboratory confirmation or epidemiological links to a confirmed case can be considered a case. WGMEC strongly urges that serological specimens be collected for all suspect cases as well as nasopharyngeal or throat and/or urine specimens for virus isolation.

REFERENCES

1. Canadian National Report on Immunization, 1997. Paediatr Child Health 1997;3(Suppl B):16-17B.

2. Measles Surveillance: Guidelines for Laboratory Support. Can Commun Dis Rep 1998;24:33-44.

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