CCDR VACCINE-PREVENTABLE DISEASES CANADA COMMUNICABLE DISEASE REPORT Research

CCDR VACCINE-PREVENTABLE DISEASES CANADA COMMUNICABLE DISEASE REPORT Research
April 7, 2016 • Volume 42-4
CCDR
CANADA COMMUNICABLE DISEASE REPORT
VACCINE-PREVENTABLE DISEASES
Research
Northern populations in Canada
are at increased risk of invasive
bacterial disease
74
There are ways to improve
the tracking of invasive
pneumococcal disease
81
Links
Updates on vaccines for malaria,
anthrax and dengue
98
CCDR
CANADA
COMMUNICABLE
DISEASE REPORT
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CCDR • April 7, 2016 • Volume 42-4
ISSN 1481-8531 Pub.150005
CCDR
CANADA
COMMUNICABLE
DISEASE REPORT
VACCINE-PREVENTABLE
DISEASES
INSIDE THIS ISSUE
SURVEILLANCE
Invasive bacterial diseases in Northern Canada,
2006-2013
74
Li YA, Martin I, Tsang R, Squires SG, Demczuk W, Desai S
EVALUATION
Evaluation of the enhanced Invasive Pneumococcal Disease
Surveillance System (eIPDSS) pilot project
81
Wijayasri S, Li YA, Squires SG, Martin I, Demczuk W, Mukhi S
OUTBREAK REPORT
Outbreak of Shigella sonnei in Montréal’s
ultra-Orthodox Jewish community, 2015
86
Pilon PA, Camara B, Bekal S
RECOMMENDATION
Interim recommendations for the reporting of
extensively drug resistant and pan-drug resistant isolates
of Enterobacteriaceae, Pseudomonas aeruginosa,
Acinetobacter spp. and Stenotrophomonas maltophilia
91
German GJ, Jamieson FB, Gilmour M, Almohri H, Bullard J, Domingo MC,
Fuller J, Girouard G, Haldane D, Hoang L, Levett PN, Longtin J, Melano R,
Needle R, Patel SN, Rebbapragada A, Reyes RC, and Mulvey MR
ID NEWS
Malaria vaccine
98
Anthrax vaccine
99
Dengue vaccine
99
100
UPCOMING
CCDR • April 7, 2016 • Volume 42-4
SURVEILLANCE
Invasive bacterial diseases in Northern
Canada, 2006–2013
Li YA1*, Martin I2, Tsang R2, Squires SG1, Demczuk W2, Desai S1
Affiliations
Abstract
Infectious Diseases Prevention
and Control Branch, Public Health
Agency of Canada, Ottawa, ON
1
Background: Northern populations are known to be at a higher risk of developing invasive
bacterial diseases (IBDs) compared with the rest of Canada. Since the last published study that
described IBDs in Northern Canada, a number of vaccines against some bacterial pathogens
have been introduced into the routine childhood immunization schedule.
Objective: To describe the epidemiology of IBDs in Northern Canada from 2006 to 2013 and
compare their incidences in the North to the rest of Canada.
National Microbiology
Laboratory, Public Health Agency
of Canada, Winnipeg, MB
2
*Correspondence: anita.li@phacaspc.gc.ca
Methods: Data for 5 IBDs (invasive pneumococcal disease [IPD], invasive Haemophilus
influenzae disease [Hi], invasive Group A streptococcal disease [iGAS], invasive meningococcal
disease [IMD] and invasive Group B streptococcal disease [GBS]) were extracted from the
International Circumpolar Surveillance (ICS) program and the Canadian Notifiable Diseases
Surveillance System. Incidence rates were calculated per 100,000 population per year.
Results: During the study period, the incidence rates of IPD ranged from 16.84–30.97,
iGAS 2.70–17.06, Hi serotype b 0–2.78, Hi non-b type 2.73–8.53, and IMD 0–3.47 per
100,000 population. Except for IMD and GBS, the age-standardized incidence rates of other
diseases in Northern Canada were 2.6–10 times higher than in the rest of Canada. Over the
study period, rates decreased for IPD (p = 0.04), and iGAS (p = 0.01), and increased for Hi
type a (Hia) [p = 0.004]. Among IPD cases, the proportion of pneumococcal conjugate vaccine
(PCV7) serotypes decreased (p = 0.0004) over the study period. Among Hi cases, 69.8% were
Hia and 71.6% of these were in children under than 5 years. Of 13 IMD cases, 8 were serogroup
B and 2 of them died. In Northern Canada, the incidence of IPD, iGAS and Hi was 2.6 to
10 times higher than the rest of Canada.
Conclusion: Northern populations in Canada, especially infants and seniors among First Nations
and Inuit, are at higher risk of IPD, Hi and iGAS than the rest of Canada. Hia is the predominant
serotype in Northern Canada.
Suggested citation: Li YA, Martin I, Tsang R, Squires SG, Demczuk W, Desai S. Invasive bacterial diseases in
Northern Canada, 2006–2013. Can Comm Dis Rep 2016;42:74-80.
Introduction
Established in 1999, the International Circumpolar Surveillance
(ICS) program is a population-based infectious disease
surveillance network of circumpolar countries including
United States, Canada, Greenland, Iceland, Norway, Sweden,
Finland and Russia (1). In Canada, Northern regions (Yukon,
Northwest Territories, Nunavut, Labrador, and Quebec Cree and
Nunavik) and a network of laboratories, including three reference
laboratories (the National Centre for Streptococcus [NCS]
(1999–2009), the Laboratoire de santé publique du Québec
[LSPQ], and the National Microbiology Laboratory [NML])
participate in the ICS program. ICS has been monitoring
invasive disease caused by Streptococcus pneumoniae (invasive
pneumococcal disease, IPD) since 1999 and invasive
Page 74
CCDR • April 7, 2016 • Volume 42-4
diseases caused by Streptococcus pyogenes (invasive Group A
streptococcal disease, iGAS), Streptococcus agalactiae (Group
B streptococcal disease, GBS), Haemophilus influenzae (Hi) and
Neisseria meningitidis (invasive meningococcal disease, IMD)
since 2000.
The demography of Northern Canada differs from the rest
of the country. In 2013, the population of Northern Canada
was estimated to be 155,666, about 0.4% of the Canadian
population. However, the proportion of self-identified
Indigenous people (First Nations, Métis or Inuit) was
approximately 60% compared to about 4% in Canada overall.
Northern populations, and especially Indigenous peoples, have
higher rates of invasive bacterial diseases (IBDs) compared with
the rest of Canada (2–6).
SURVEILLANCE
The last published study describing IBDs in Northern Canada
included data from 1999 to 2005 (5). Since then, a number
of vaccines against some bacterial pathogens have been
introduced into the routine childhood immunization schedule.
In Canada, the National Advisory Committee on Immunization
(NACI) recommends vaccines and their schedules, but the
implementation of vaccine programs varies among provinces and
territories. For IPD, routine infant vaccine programs for
7‑valent pneumococcal conjugate vaccine (PCV7) began in
2002 and were fully implemented across Northern Canada by
January 2006 (7). The IPD vaccine programs began replacing
PVC7 with 10-valent pneumococcal conjugate vaccine (PCV10) in
2010. By January 2011, all six regions were using
13-valent pneumococcal conjugate vaccine (PCV13) in their
infant IPD vaccine programs. The 23-valent pneumococcal
polysaccharide vaccine (PPV23) is used for targeted populations
such as people aged 65 years and over and those at risk for IPD
(8). Routine infant vaccine programs for Hi type b have been
implemented since 1997 (8). For IMD, routine infant vaccine
programs of meningococcal C conjugate vaccine (MenC) [9] have
been implemented in all six regions as of 2007.
The objective of this report is to describe the epidemiology of
IBDs in Northern Canada from 2006 to 2013 and compare their
incidences in the North to the rest of Canada.
Methods
Epidemiological data
from Difco Laboratories (BD Diagnostics, Falcon Lakes,
New Jersey, USA), and the results were confirmed by polymerase
chain reaction (PCR) [14]. Non-typeable strains of Hi were
confirmed by 16S ribosomal RNA sequencing (15). Serogrouping
of N. meningitidis was performed using bacterial agglutination
methods (16). All reference laboratories participate in an
ongoing ICS quality control program (17).
Population data
General population estimates were obtained from
Statistics Canada (18). Because Statistics Canada only
provides Indigenous population estimates for 2006 and 2011
census years, aggregated Indigenous (First Nations, Métis
or Inuit) population estimates in this report were obtained
from territorial/regional statistics departments. Indigenous
population estimates for Labrador and Quebec Cree could only
be estimated based on 2006 and 2011 census data. Population
estimates of separate Indigenous groups were not available for
this report. The 1991 Canadian population was chosen as the
standard population for age standardization. The population
distribution is based on the final post-Census estimates
for July 1, 1991, Canadian population, adjusted for census
undercoverage. The age distribution of the population has been
weighted and normalized (19).
Data used in this report came from public health surveillance and
were exempt from research ethics board approval.
Analysis
Surveillance data for Northern Canada and the rest of the
country were extracted from ICS and the Canadian Notifiable
Diseases Surveillance System (CNDSS), respectively, with disease
onset between January 1, 2006 and December 31, 2013. Only
cases that met the national case definitions (10) were included.
ICS regional coordinators complete disease‑specific Bacterial
Disease Surveillance Forms (BDSFs) for cases that meet the
national case definitions (10) and then collate and review
laboratory information. Data included within the BDSF include
non‑nominal demographic information, clinical information,
outcomes, risk factors and immunization history. Completed
BDSFs and laboratory reports are sent to the Public Health
Agency of Canada using a secure process. CNDSS receives
aggregated data containing basic non-nominal demographic
information from provinces and territories annually.
The demographic data, serotype distributions, as well as clinical
characteristics, and immunization status of the IBD cases were
examined. Incidence rates for GBS of the newborn were not
calculated since annual live births estimates of Northern regions
were not available for this report. All incidence rates were
per 100,000 population per year. Direct method was used for
calculating age-standardized rates. Confidence intervals (CIs) of
age-standardized rates were calculated with the method based
on the gamma distribution (20). Cases with missing age were
excluded from age standardization. The Chi-squared test and
Fisher’s exact test were used to compare proportions. Poisson
regression was used to compare incidence rates and estimate
disease trends. Statistical significance was considered at the
95% confidence level. Descriptive and inferential analyses were
conducted using Microsoft Excel 2010 and SAS EG 5.1.
Laboratory data
Results
Invasive isolates were submitted to NML, NCS (2006–2009)
or LSPQ for characterization. Serotyping of S. pneumoniae
using the Quellung reaction was performed using commercial
pool, group, type and factor antisera from SSI Diagnostica,
Statens Serum Institut, Copenhagen, Denmark (11,12). The
emm sequence types for iGAS isolates were determined using
the methodology recommended by the United States Centers
for Disease Control and Prevention (CDC) [13]. GBS serotypes
were determined using commercial latex-agglutinating antisera
from SSI Diagnostica (11,12). Serotyping of H. influenzae was
accomplished using bacterial agglutination test with antisera
Overview
From 2006 to 2013, the total number of confirmed cases
reported in Northern Canada was 270 IPD, 110 iGAS,
109 Hi, 13 IMD and 8 GBS of the newborn. The demographic
information for cases of each disease is noted in Table 1. A total
of 46 IBD related deaths were reported.
CCDR • April 7, 2016 • Volume 42-4
Page 75
SURVEILLANCE
Table 1: Demographic distributions of invasive bacterial
diseases in Northern Canada, by disease, gender and
ethnicity, 2006–2013
Median
age,
years
(range)1
Disease
(total
number)
IPD
(N=270)
39
(0–92)
iGAS
(N=110)
Hi
(N=109)
IMD
(N=13)
GBS
(N=8)
41
(0–90)
1
(0–80)
0
(0–56)
0
(0–88)
Figure 1: Invasive pneumococcal disease serotype
distribution by year and incidence rates
(per 100,000 population) by year and ethnicity in
Northern Canada, 2006–20131,2
Number of cases (%)
Sex2
(male/
female)
Ethnicity3
First
Nations
Inuit
NonIndigenous
142/127
114 (46)
94 (38)
3 (1)
36 (15)
61/49
50 (48)
44 (42)
0
11 (10)
59/50
28 (11)
74 (72)
0
1 (1)
5/8
4 (31)
6 (46)
0
3 (23)
5/3
3 (38)
4 (50)
0
1 (12)
Métis
Abbreviations: GBS, Group B streptococcal disease; Hi, Haemophilus influenzae;
iGAS, invasive Group A streptococcal disease; IMD, invasive meningococcal
disease; IPD, invasive pneumococcal disease
1
Two cases with unknown age were excluded
2
One case with unknown sex was excluded
3
Thirty-five cases with unknown ethnicity were excluded
Table 2 shows the annual crude incidence rates of the diseases
in Northern regions as well as the age-standardized rates for
both Northern regions and the rest of Canada. Except for IMD,
age-standardized incidence rates of IPD, iGAS and Hi were
significantly higher in Northern regions.
Disease-specific
Invasive pneumococcal disease (IPD)
The age-standardized incidence rate (per 100,000 population) of
IPD decreased significantly over the report period
(p = 0.04) [data not shown]. The age-standardized incidence
rates were similar for males (23.55, CI: 19.65–28.10) and females
(23.40, CI: 19.31–28.22). The annual incidence rate (per 100,000
population) was highest for infants less than 1 year old
(132.68, CI: 88.96–190.55), children aged 1 to 4 years
(49.53, CI: 35.70–66.96) and adults 60 years and older (47.85, CI: 35.84–62.59). The average annual incidence rate was
29.51 (range: 22.13–37.12) for those of Indigenous origin and
7.57 (range: 3.18–13.23) for those of non-Indigenous origin, and
this difference was significant (p < 0.0001) [Figure 1].
Abbreviations: IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine; PPV,
pneumococcal polysaccharides vaccine
1
PCV7 serotypes: 7 serotypes included in PCV7, i.e., serotype 4, 6B, 9V, 14, 18C, 19F, and 23F;
PCV13 serotypes: additional 6 serotypes included in PCV13 compared to PCV7, i.e., serotype
1, 3, 5, 6A, 7F, and 19A; PPV23 serotypes refers to additional 11 serotypes included in PPV23
compared to PCV13, i.e., serotype 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F
2
A total of 23 cases without ethnicity information were excluded from the incidence calculation
Figure 1 also shows that the proportional distributions of IPD
serotypes have changed over the years. The proportion of PCV7
serotypes decreased significantly from 37% (n=10) in 2006 to
4% (n=1) [p = 0.0004] in 2013. There have been no cases of
PCV7 serotypes under 2 years of age since 2009. Of the cases
in this group, the proportion of the additional PCV13 serotypes
was 26% before 2011 and 21% after 2011 and the change was
not significant (p = 0.49). From 2006 to 2013, the most common
serotypes were 8 (13.9%), 7F and 19A (6.6% each), 12F (6.0%),
and 3, 14, 22F (5.4% each). After 2010, the most common
Table 2: Crude and age-standardized incidence rates (per 100,000 population) of invasive bacterial diseases in
Canada, by disease, region and year, 2006–20131
Age-standardized incidence rates
(95% CI)
Crude incidence rates
Disease
Northern regions2
Rest of Canada2
2006–2013
2006–2013
2006
2007
2008
2009
2010
2011
2012
2013
IPD
18.73
30.97
23.20
30.42
20.66
22.96
16.84
17.35
23.59 (20.72–26.80)
8.68 (8.57–8.79)
iGAS
12.49
9.63
17.06
2.70
8.00
7.87
9.07
7.07
10.86 (8.83–13.26)
4.20 (4.12–4.28)
2.78
0.69
2.05
0.68
0.00
0.66
0.65
0.64
0.89 (0.45–1.71)
0.09 (0.08–0.10)
Hi non-b
7.63
6.88
2.73
6.76
11.33
8.53
7.77
10.92
IMD
3.47
0
0.68
0.68
0.67
1.31
1.30
0.64
Hib
3
4
8.13 (6.26–10.48)
0.95 (0.89–1.01)4
0.87 (0.46–1.63)
0.55 (0.52–0.58)
Abbreviations: CI, confidence interval; Hib, Haemophilus influenzae type b; Hi non-b, Haemophilus influenzae type OTHER; iGAS, invasive Group A streptococcal disease;
IMD, invasive meningococcal disease; IPD, invasive pneumococcal disease
1
Two invasive Hi disease cases with missing serotype and 1 IPD case with missing age were excluded from the incidence rate calculation
2
Age-standardized rates and CIs are bolded when the differences between Northern regions and the rest of Canada are significant
3
For the purpose of comparison, Hi non-b serotypes were grouped into one category to match the national data in Canadian Notifiable Diseases Surveillance System
4
Age-standardized incidence rates for invasive Hi non-b disease do not include data of 2007–2008
Page 76
CCDR • April 7, 2016 • Volume 42-4
SURVEILLANCE
serotypes were 7F (16.5%), 10A (11.4%), 19A, 22F and 33F
(7.6% each), and 11A (5.1%).
Of the 44 cases who had been vaccinated with PCV7, the 2 who
had PCV7 serotypes were not fully vaccinated at the time of
illness. All of the 6 cases who had been vaccinated with PCV10
had non-PVC10 serotypes. Of the 13 cases who had been
vaccinated with PCV13, only one had a PCV13 serotype and that
case had not been fully vaccinated, i.e., had not received all
4 doses. Of the 70 cases that had PPV23, 20 (29%) were infected
with non-vaccine serotype and 5 (7%) with unknown serotype.
In total, 87.4% (n=236) of IPD cases were hospitalized. The most
common clinical syndromes (Table 3) were pneumonia (68.2%),
septicemia/bacteremia (50.4%) and meningitis (7.4%). The overall
case-fatality ratio (CFR) was 11.0% (n=28). The majority of the
fatal cases were individuals aged 40 and 59 years
(46.4%, n=13) and 60 years and older (35.7%, n=10). Individuals
in these two age groups with IPD had significantly higher risk
for death (CFR=18.1%) than those in younger age groups
(CFR=3.9%, p = 0.0003). The fatality ratio did not vary between
cases in Indigenous and non-Indigenous people (p = 0.78).
Among 26 fatal cases with serotype information, the majority
were PPV23 serotypes (46.2%, serotypes are not included in
PCV13) and non-vaccine serotypes (34.6%).
Table 3: Common clinical manifestations and outcomes
of cases of invasive pneumococcal disease, invasive
Group A streptococcal disease, Haemophilus influenzae
type b, invasive meningococcal disease and
Group B streptococcal disease of the newborn in
Northern Canada in 2006‑20131
Manifestation and
outcome
Septicemia/
Bacteremia
Meningitis
Pneumonia
Number of cases (%)
IPD2
(n=258)
iGAS
(n=106)
Hi
(n=102)
IMD3
(n=13)
GBS3
(n=8)
130 (51.2)
42 (40.8)
36 (38.3)
4
6
19 (7.5)
0
24 (25.5)
8
2
176 (69.3)
17 (16.5)
41 (43.6)
2
2
Empyema
7 (2.8)
7 (6.8)
2 (2.1)
0
0
Septic arthritis
4 (1.6)
11 (10.7)
11 (11.7)
1
0
Necrotizing
fasciitis
0
10 (9.7)
0
0
0
Cellulitis
0
33 (32.0)
6 (6.4)
0
0
28 (11.0)
8 (7.8)
8 (8.5)
2 (15.4)
0
Death4
(11.86, CI: 8.94–15.51) and females (9.72, CI: 7.07–13.14). The
annual incidence rate (per 100,000 population) was the highest
for infants under 1 year of age (41.18, CI: 18.83–78.17) and
adults aged 60 years and older (47.85, CI: 35.84–62.59), and
children aged 1 to 4 years (11.79, CI: 5.66–21.69). The annual
incidence rate ranged between 2.25 and 20.44 for Indigenous
peoples and between 0 and 6.80 for non-Indigenous people, and
the rate was significantly higher for Indigenous peoples
(p < 0.0001).
Isolates of 74 iGAS cases were emm typed, and the most
common types were emm59 (10.8%), emm1 and emm91
(9.5% each) and emm41 (6.8%). Nighty-two percent (n=101) of
cases were hospitalized. As shown in Table 3, the most common
manifestations were septicemia/bacteremia (39.6%) and cellulitis
(31.1%). Pneumonia (16%), septic arthritis (10.4%), necrotizing
fasciitis (9.4%) and empyema (6.6%) were also commonly seen.
The overall CFR was 7.8% (n=8) and all fatal cases (except 1 with
unknown ethnicity) were in Indigenous peoples. The emm types
of the fatal cases were all different.
Invasive Haemophilus influenzae disease (Hi)
Overall, there were no significant changes in the
age-standardized annual incidence rates of Haemophilus
influenzae type b (Hib) (p = 0.18) or Hi non-b (p = 0.15) from
2006 to 2013. Except for 6 cases with missing ethnicity and 1
non-Indigenous case, all the other 102 cases were First Nations
and Inuit people. Of the 12 Hib cases, 10 were under 18 months
of age; 4 had completed their primary vaccine series, 5 had
received the vaccine but were not up-to-date and 1 was not
vaccinated.
Figure 2 shows the serotype distribution of Hi cases. During the
study period, Hi type a (Hia) accounted for 69.8% of the cases,
followed by Hib (11.3%) and Hi non-typable (10.4%). No
serotype e cases were reported. The annual incidence rate (per
100,000 population) of Hia increased significantly (p = 0.004)
from 2006 to 2013. Fifty-three (71.6%) of Hia cases were in
children under than 5 years. The incidence rate of Hia was the
highest for infants less than 1 year (132.68, CI: 88.86–190.55),
followed by children aged 1 to 4 years (28.31, CI: 18.14–42.12).
In total, 87.5% (n=91) of Hi cases were hospitalized. The most
common manifestations (Table 3) were pneumonia (38.7%),
septicemia/bacteremia (34.0%), meningitis (22.6%), and septic
arthritis (10.4%). The overall CFR was 8.5% (n=8) and all fatal
cases were of Hia.
Abbreviations: GBS, Group B streptococcal disease; Hi, Haemophilus influenzae;
iGAS, invasive Group A streptococcal disease; IMD, invasive meningococcal disease;
IPD, invasive pneumococcal disease
1
For each disease, the total percentage of manifestation could be more than 100% due to the
multiple manifestations for an individual case
2
For IPD, pneumonia refers to pneumonia with bacteremia
3
Due to the small total number of cases, the proportions of manifestation were not calculated for
IMD and GBS of the newborn
4
The total number of cases where outcome information is available was: 254 (IPD), 103 (iGAS),
94 (Hi), 13 (IMD), and 7 (GBS)
Invasive meningococcal disease (IMD)
Invasive Group A streptococcal disease (iGAS)
Invasive Group B streptococcal disease (GBS) of the newborn
The age-standardized annual incidence rate of iGAS decreased
significantly (p = 0.01) over the report period. Of 110 iGAS cases,
61 were male and 49 female. The age-standardized incidence
rates (per 100,000 population) were similar for males
Of 8 cases of GBS of the newborn, 6 were early onset and
2 were late onset. The serotyping information was available for
only 3 cases, 1 serotype Ia and 2 serotype III.
Septicemia/bacteremia was the most common manifestation
Of 13 IMD cases, 8 were serogroup B (all under 5 years of age),
2 were C (both between 40 and 59 years) and 3 were W (all
under 10 years of age). In terms of manifestation, 4 cases had
meningitis only, 4 had meningitis with septicemia/bacteremia or
other conditions, 2 had septicemia/bacteremia only (Table 3).
Two cases died; both had serogroup B.
CCDR • April 7, 2016 • Volume 42-4
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SURVEILLANCE
Figure 2: Serotype distribution of invasive Haemophilus
influenzae disease cases and serotype specific incidence
rates in Northern Canada, by year, 2006–20131
conditions of Indigenous children may be potential risk factors
(28‑31). Hia has been a predominant serotype in Northern
Canada since the beginning of ICS (5,22,32), whereas
non‑typaeble Hi and type f are more common in other
circumpolar regions (32). This report also demonstrates the
significant increasing trend of Hia. National data of Hi non-b
types are aggregated into a single category, so the serotype
specific trends and distributions of Northern Canada and the rest
of the country cannot be compared.
IMD is generally rare in Northern Canada as well as the rest
of the country (33). Since the implementation of childhood
immunization programs for MenC, the incidence of
meningococcal C is at an all‑time low and meningococcal B is
the predominant serotype in Canada (33). None of the cases
reported during the study period could have been prevented by
the vaccine programs at the time.
Abbreviations: NT, non-typeable; Hia, Haemophilus influenzae type a; Hi NT, Haemophilus
influenzae non-typeable
1
Three cases with serotype missing were excluded
(n=6), followed by meningitis (n=2) and pneumonia (n=2)
(Table 3). No deaths were reported.
Discussion
In Northern Canada, the incidence of IPD, iGAS and Hi was
2.6 to 10 times higher than in the rest of Canada, especially
among First Nations and Inuit people. These findings are
consistent with previous Canadian and international circumpolar
studies (3-6,21-23).
IPD accounted for half of the IBDs cases during the study period
and continues to be a substantial cause of morbidity in
Northern Canada, especially for infants and people aged
60 years and greater. The risk of death did not vary between
Indigenous and non-Indigenous peoples.
Routine PCV7 vaccination of infants started in 2002 in some
Northern regions and IPD incidence has reduced since then
(5,6). This report demonstrates a further reduction and sustained
decreasing trend in PCV7 serotype-caused IPD as well as the
total incidence of IPD. The incidence of IPD caused by PCV13
has not changed. More longitudinal data are needed for further
assessment of PCV13. The efficacy and effectiveness of PPV23,
which differs from conjugated vaccines, are relatively lower
(24-26), and the protection of PPV23 appears to wane after
5 years (27). It is not surprising to see cases in individuals who
had been immunized.
Routine Hib vaccine programs have been implemented in
Canada since 1997 (8) and (Hib) is now rare in the country.
However, it is still a concern in Northern Canada with a
substantially higher rate among Indigenous infants. Some
studies suggested that poor health, environmental and housing
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CCDR • April 7, 2016 • Volume 42-4
The incidence of iGAS increased between 1999 and 2005 (5,32)
but decreased between 2006 and 2013. This change in trend
should be interpreted with caution due to the small number of
cases. The most common emm types were emm1,
emm59 and emm91, similar to the distribution reported between
1999 and 2005 (5) and the rest of Canada (34), but different than
that of other circumpolar regions such as Alaska where emm3,
emm41 and emm12 were more common (5,32).
Due to the lack of live birth population data and extremely small
number of cases of GBS of the newborn, it is difficult to compare
the disease epidemiology between Northern Canada and the
rest of Canada or other countries.
It is important to consider the limitations when interpreting the
data in this report. The disease characteristics, e.g., serotyping,
outcomes and immunization history, could be underestimated
or overestimated due to missing data. The analyses of GBS and
IMD were limited due to the extremely small case numbers and
the lack of live birth population data. Due to the instability of
results based on the small number of cases and small population
sizes, caution should be used when interpreting results. Finally,
further detailed analysis of Inuit, First Nations and Métis
individuals was not possible due to small numbers and the lack of
availability of population estimates of these individual groups in
the ICS region.
Compared to the rest of Canada, data indicate that Northern
Canada has higher incidence rates of IPD, Hi and iGAS,
especially among infants and seniors. First Nations and Inuit
groups are more vulnerable to the diseases than non-Indigenous
people. Enhanced national surveillance of IBDs is needed to
better understand the disease disparities between Northern
Canada and the rest of the country. In Canada, ICS is the only
surveillance system that captures both epidemiological and
laboratory data on IBDs for Northern populations. Ongoing
surveillance will contribute to the understanding of disease
epidemiology, which will ultimately assist in the formulation
of prevention and control strategies, including immunization
recommendations, for Northern populations.
SURVEILLANCE
Acknowledgements
We would like to thank all members of the Canadian
International Circumpolar Surveillance Invasive Bacterial Diseases
Working Group, particularly A. Mullen, B. Lefebvre, C. Cash,
C. Foster, G. Tyrrell, H. Hannah, J. Proulx, K. Dehghani,
Y. Jafari, for their invaluable contribution to the ICS surveillance
and to this report. We would also like to thank J. Cunliff and
M. St‑Jean for database management and N. Abboud for project
management.
Conflict of interest
None.
Funding
10. Public Health Agency of Canada. Case definitions for
communicable diseases under national surveillance. Can
Comm Dis Rep 2009;35-Suppl 2:1-123.
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pneumoniae infections: serotype distribution and
antimicrobial resistance in Canada, 1992-1995. CMAJ. 1998
Feb 10;158(3):327-31.
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laboratory. Protocol for emm typing. Atlanta (GA): The
Centers; 2015 Feb 26. http://www.cdc.gov/streplab/
protocol-emm-type.html.
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ER. PCR for capsular typing of Haemophilus influenzae. J
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Funding for Canada’s participation in International Circumpolar
Surveillance was paid for by the Public Health Agency of Canada.
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al. Characterization of Haemophilus segnis, an important
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3. Christiansen J, Paulsen P, Ladefoged K. Invasive
pneumococcal disease in Greenland. Int J Circumpolar
Health 2004;63 Suppl 2:214-218.
4. Singleton R, Hammitt L, Hennessy T, Bulkow L, DeByle C,
Parkinson A, et al. The Alaska Haemophilus influenzae type
b experience: lessons in controlling a vaccine-preventable
disease. Pediatrics. 2006 Aug;118(2):e421-9.
5. Degani N, Navarro C, Deeks SL, Lovgren M. Invasive
bacterial diseases in northern Canada. Emerg Infect Dis.
2008 Jan;14(1):34-40.
6. Bruce MG, Deeks SL, Zulz T, Navarro C, Palacios C, Case C,
et al. Epidemiology of Haemophilus influenzae serotype a,
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Jan;14(1):48-55.
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Update on the invasive pneumococcal disease and
recommended use of conjugate pneumococcal vaccines.
Can Comm Dis Rep 2010; 36(ACS-3):1-30.
8. Public Health Agency of Canada. Canadian Immunization
Guide. Ottawa (ON). http://www.phac-aspc.gc.ca/publicat/
cig-gci/index-eng.php.
9. National Advisory Committee on Immunization (NACI).
An update on the invasive meningococcal disease and
meningococcal vaccine conjugate recommendations. An
Advisory Committee Statement (ACS). Can Comm Dis Rep
2009; 36 (ACS-3):1-40.
17. Tsang RS, Rudolph K, Lovgren M, Bekal S, Lefebvre B,
Lambertsen L, et al. International circumpolar surveillance
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Haemophilus influenzae and serogrouping Neisseria
meningitidis, 2005 to 2009. J Clin Microbiol. 2012
March;50(3):651-6.
18. Statistics Canada, Demography Division, Demographic
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24. Melegaro A, Edmunds WJ. The 23-valent pneumococcal
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30. Kovesi T, Creery D, Gilbert NL, Dales R, Fugler D, Thompson
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G, et al. Lower respiratory tract infections in Inuit infants on
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ME, et al. Risk factors for acute respiratory tract infections
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Laboratory. National Laboratory Surveillance of
Streptococcal Diseases In Canada - Annual Summary 2013.
2014.
EVALUATION
Evaluation of the enhanced Invasive
Pneumococcal Disease Surveillance System
(eIPDSS) pilot project
Wijayasri S1,2, Li YA2, Squires SG2*, Martin I3, Demczuk W3, Mukhi S3
Affiliations
Abstract
University of Saskatchewan, School
of Public Health, Saskatoon, SK
1
Background: Invasive pneumococcal disease (IPD) causes significant morbidity in Canada, yet
with routine surveillance, it is difficult to interpret current IPD trends in serotype distribution
and antimicrobial resistance. The enhanced Invasive Pneumococcal Disease Surveillance
System (eIPDSS) pilot project was designed to facilitate a better understanding of IPD trends
at the national level by linking epidemiologic and laboratory (epi-lab) data.
Objectives: To evaluate the eIPDSS by assessing five attributes (usefulness, data quality,
simplicity, acceptability and timeliness) and to develop recommendations for future national
IPD surveillance.
Infectious Diseases Prevention
and Control Branch, Public Health
Agency of Canada, Ottawa, ON
2
National Microbiology Laboratory,
Public Health Agency of Canada,
Winnipeg, MB
3
*Correspondence: susan.squires@
phac-aspc.gc.ca
Methods: An evaluation was developed that assessed the five key attributes through a
qualitative survey sent to eight eIPDSS users as well as a quantitative analysis of the eIPDSS
database. Recommendations were based on the results of both the survey and the analysis.
Results: The response rate to the survey was 100%. The majority of the survey respondents
found the eIPDSS to be useful (75%), simple (100%) and acceptable (86%). Analysis of the
eIPDSS database revealed that the majority of IPD cases (61%) were assessed as timely.
Data quality and data management mechanisms were identified as issues by both survey
respondents and the analysis of the database. Consultation with public health, regular audits
and upgrades to the platform are recommended to address data quality and management
issues.
Conclusion: The epi-lab linked data of the eIPDSS enables the detection and analysis of IPD
serotype distribution and antimicrobial resistance trends. This web-based system facilitates
data collection and is simple, acceptable and timely. With improvements that address data
quality and management issues, it is feasible to develop a national surveillance system that
links epi-lab data.
Suggested citation: Wijayasri S, Li YA, Squires SG, Martin I, Demczuk W, Mukhi S. Evaluation of the enhanced
Invasive Pneumococcal Disease Surveillance System (eIPDSS) pilot project. Can Comm Dis Rep 2016; 42:81-5.
Introduction
Invasive pneumococcal disease (IPD) is an infectious disease
caused by Streptococcus pneumoniae, which can cause severe
morbidity and mortality, especially among young children and
the elderly. Globally, an estimated 1.6 million people, including
one million children less than five years of age, die of IPD
annually (1). IPD has been nationally notifiable in Canada since
2000 (2) and is vaccine-preventable. Currently in Canada, a
publicly funded pneumococcal conjugate 13 (PCV13) vaccine
is available for infants and the pneumococcal polysaccharide
vaccine (PPV23) is available to adults over the age of 65 and
those considered at high risk for IPD (3).
There are currently 92 serotypes of S. pneumoniae recognized
worldwide, 15 of which cause the majority of disease in Canada.
Approximately 50 different serotypes are identified each year
(4). The two vaccines cover the 24 most common serotypes (4).
While Canada is experiencing a decrease in incidence of IPD that
is reflective of an effective immunization program (5), the rising
incidence of non-vaccine serotypes and antimicrobial resistan
(AMR) serotypes are of particular concern.
Historically, epidemiologic and laboratory (epi-lab) linked data
have not been available at the national level. The concept for the
enhanced Invasive Pneumococcal Disease Surveillance System
(eIPDSS) pilot project was devised to address shortcomings in
the current routine surveillance methods, namely the inability
to identify integrated epidemiologic and laboratory trends to
provide evidence for vaccination programs and detect AMR
serotype trends. The eIPDSS pilot project was launched in
New Brunswick in April 2011 to allow for enhanced surveillance
that would foster a better understanding of IPD trends,
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EVALUATION
especially changes in serotype distribution and antimicrobial
resistance (AMR). This innovative project promoted collaborative
working relationships between the provincial and the federal
public health programs and allowed for the technological
transformation and modernization of IPD surveillance.
The Canadian Network for Public Health Intelligence’s (CNPHI)
Web Data technology was used to rapidly develop the pilot
system platform. Although Web Data technology is not typically
used for long-term surveillance systems, it was selected due to
its ability to rapidly and interactively set up a database and the
inherent flexibility required for the pilot phase (6).
The eIPDSS process and platform
The objective of this study was to evaluate the eIPDSS pilot
project by assessing five surveillance attributes — usefulness,
data quality (completeness and validity), simplicity, acceptability
and timeliness — and provide recommendations to improve
these attributes to inform the development of national
integrated surveillance systems that link epi-lab data.
This pilot was jointly managed by the National Microbiology
Laboratory (NML) and the Centre for Immunization and
Respiratory Infectious Diseases (CIRID) of the Public Health
Agency of Canada, partners at the New Brunswick Ministry of
Health and regional hospital laboratories and regional public
health. The data collection process involved three points of
entry – the local healthcare facilities, the NML, and regional
and provincial public health offices. Figure 1 presents the data
process of the eIPDSS, from specimen collection to completion
of the electronic record. The NML posted laboratory information
on the different serotypes onto the eIPDSS platform, which
the provincial epidemiologist linked to the epidemiological
information, including vaccination history and risk factors using
a unique identifier or through probabilistic matching. These data
were then readily available for extraction by all
federal- and provincial- level surveillance partners through the
platform.
Methods
An evaluation framework was developed using guidelines
outlined in Health Canada’s Framework and Tools for Evaluating
Health Surveillance Systems (7) and the Updated Guidelines for
Evaluating Public Health Surveillance published by the Centers
for Disease Control and Prevention (CDC) [8]. This framework
was designed to assess five important attributes -- usefulness
and data quality were selected to assess whether the eIPDSS is
effective in collecting epi-lab linked data; simplicity, acceptability
and timeliness were selected to assess the feasibility of
Figure 1: Data flow process of enhanced Invasive Pneumococcal Disease Surveillance System pilot project,
2011–2015
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CCDR • April 7, 2016 • Volume 42-4
EVALUATION
developing a national IPD surveillance system that links
epidemiologic and laboratory data.
the episode date and the date of report to the system was
determined and examined for each case.
These attributes were assessed through a combination of two
approaches: 1) a qualitative, anonymous survey and 2) a detailed
analysis of the pilot project’s data flow process, database
and operations. The survey was sent to eight primary eIPDSS
users who used the system regularly (four provincial-level
epidemiologists and surveillance analysts in New Brunswick and
four federal-level epidemiologists at CIRID and laboratorians at
the NML). The analysis was conducted by the authors.
The recommendations were developed by the authors based on
the results of the evaluation, including feedback from primary
users.
The following outlines how each attribute was assessed:
Usefulness: A surveillance system is considered useful if it
contributes to the prevention and control of adverse health
related events (8). To assess the various “usefulness indicators”
outlined by the CDC guidelines, the system’s operations and
objectives were reviewed and a quantitative analysis of the data
was performed. Survey respondents also answered questions
specific to how they use the system and its data, their opinions
on the usefulness of the eIPDSS data, how the system could be
made more appropriate to their needs and whether the pilot
project was or could be made ready for national implementation.
Data quality: Data quality was assessed through three indicators:
the application of a uniform national case definition (see box
below), completeness of the data elements and validity of the
captured cases. Completeness was assessed by calculating
the percentage of missing values (both “unknown” and blank
responses) of selected data elements. Validity was assessed
by comparing the counts of IPD cases from New Brunswick
captured in the Canadian Notifiable Disease Surveillance System
(CNDSS) with data from the eIPDSS.
Case definition of invasive pneumococcal disease (9)
A confirmed case is when there is clinical evidence of invasive
disease with laboratory confirmation of infection:
•
•
Isolation of Streptococcus pneumoniae from a normally
sterile site (excluding the middle ear and pleural cavity)
OR
Demonstration of S. pneumoniae DNA from a normally
sterile site (excluding the middle ear and pleural cavity)
Abbreviation: DNA, deoxyribonucleic acid
Simplicity: This refers to the ease of data flow and management
of the system (8) and was assessed through the stakeholder
survey, using questions concerning ease of use, user opinions
on features that facilitate or hinder simplicity and reliability of
the system to collect, manage and access data properly without
failure.
Acceptability: This refers to the willingness of surveillance staff
to implement the system and users of the system to use the
data generated (8). Acceptability was assessed through the
stakeholder survey using questions related to features of the
system that promoted or prevented acceptance.
Results and recommendations
Participation in the eIPDSS evaluation survey was 100%.
Usefulness
Six of the survey respondents (75%) felt that the eIPDSS data
were useful. None of the data elements were identified as
not useful. A quantitative analysis of the eIPDSS data also
revealed that the eIPDSS was useful. The system was able to
capture all confirmed cases of IPD—it detected epidemiologic
and laboratory trends and was able to provide estimates of
magnitude of IPD morbidity and mortality.
Recommendations to improve usefulness:
1. Discuss with surveillance partners the inclusion of the
following elements to provide more detailed
morbidity / mortality information:
a. Intensive care unit admissions
b. Outbreak indicator
c. Date of death
2. Review the current data dictionary and case report form with
surveillance partners to reflect necessary changes.
Data quality
Of the 273 cases with episode dates between April 4, 2011 and
June 8, 2015, 98% (n=267) met the national case definition.
Six cases were removed from the dataset because they did not
meet the national case definition—two had pleural fluid isolates
and four had pneumonia without an accompanying positive
blood isolate.
Completeness of several data elements was below the
pre-established satisfactory level of 90%, including clinical
diagnosis (81%), length of hospital stay (88%), outcome (86%),
underlying medical conditions (73%), Indigenous status (45%)
and immunization history (71% to 73%). The use of a unique
identifier for linking laboratory and epidemiologic dataset
was considerably below the satisfactory level of completeness
(34%) and follow-up with provincial surveillance partners
revealed that obtaining a unique identifier to link laboratory and
epidemiological data was problematic. However, 63% of the
survey respondents found the data to be sufficiently complete,
with AMR data collection and immunization history identified as
areas that needed improvement.
Comparison between data from the CNDSS and eIPDSS found
100% agreement between case counts by each age group and
sex, demonstrating that the eIPDSS data are valid.
Timeliness: Timeliness reflects the speed or delay between
steps in a surveillance system (8). The number of days between
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EVALUATION
Recommendations to improve data quality and completeness:
Acceptability
1. Consult with regional public health offices on ways to
improve the collection of important data elements,
especially clinical diagnosis and immunization history.
All eight respondents answered questions addressing
acceptability. Seven (88%) indicated the system was acceptable
or highly acceptable. Comments, however, identified difficulties.
Editing of case information, data cleaning and
assigning/removing duplicates were identified as barriers to
acceptability at the provincial level. The security of the dataset
was identified as a concern due to the lack of restriction of
certain data elements (i.e., date of birth, geographical region). In
addition, difficulties in collecting data from the regions were also
a concern. Specifically, the collection of certain data elements, as
well as restrictions to AMR testing in many of the regions, were
identified as barriers to acceptability.
a. Establish data quality indicators. A suggested indicator,
currently used by the CDC, could be the proportion of
reported cases with complete information, based on an
established minimum dataset (10). This indicator could
inform consultation with regional offices.
2. Include a “Record status” variable to distinguish confirmed
cases from discarded cases.
3. A follow-up process should be developed, documented and
agreed upon to maintain a high level of data quality and
completeness and to improve responsiveness of the system.
This follow-up process should include:
a. An annual data audit.
b. A mechanism to allow for changes in case information
(e.g., changes to province of residence, errors,
duplicates, etc.) that will be reflected on both
laboratory and epidemiological sides.
c. Agreed-upon delegation of follow-up responsibilities
among eIPDSS surveillance partners.
4. Should the provincial and national case definitions differ,
ensure that the eIPDSS is able to capture both provincial
and national case definitions and filter cases accordingly.
Consult with provincial public health to ensure that
provincial case report forms include all data elements
required for the assessment of the national case definition.
Simplicity
Seven respondents answered questions related to simplicity.
All agreed that the current system was simple or very simple.
However, respondents identified concerns due to difficulties
with data uploading and extraction (possibly attributed to
complexities with data management processes), as well as the
use of probabilistic matching (matching variables such as age,
sex and episode date) rather than the use of a unique identifier
to link laboratory and epidemiologic datasets. These difficulties
were identified as barriers to simplicity.
Recommendations to improve simplicity:
1. Migrate the eIPDSS from Web Data technology to a more
dedicated custom application on the CNPHI informatics
platform that allows for:
a. Automated epidemiologic and laboratory record
linkage that enables easier data linking and eliminates
the current practice of probabilistic matching.
b. Extraction of data through filtering of elements.
c. Summarized data reports and statistical analysis.
d. Faster performance (uploading and extracting data).
2. Consult with regional public health offices to ensure NML
laboratory numbers are recorded on the case report form
and reported to the provincial ministry of health.
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CCDR • April 7, 2016 • Volume 42-4
Recommendations to improve acceptability:
1. Review data-sharing mechanisms and discuss the restriction
of certain variables to surveillance partners (e.g., date of
birth, geolocator/postal codes).
2. Revisit and review AMR testing arrangements with regional
public health offices.
Timeliness
The time between episode date and date of report ranged
from six business days (from January to June 2015) to 18 days
(from April to December 2011), with an average of 10 days for
the entire pilot period. The majority of the cases (61%) were
reported to the local public health office within seven business
days of the episode date. Laboratory data were uploaded
to the CNPHI Web Data technology on a weekly basis, while
epidemiological information was updated quarterly. The eIPDSS
was deemed as timely.
Recommendations to improve timeliness:
None.
Considerations for national implementation
Seven of the eight survey respondents answered questions
regarding the national implementation of eIPDSS, of which six
(75%) said that the pilot is or could be made ready for national
implementation. Considering the simplicity, acceptability,
usefulness and timeliness of the system, as well as the positive
responses towards national expansion by the surveillance
partners, the eIPDSS could be expanded nationally after
improvements are made based on the recommendations.
In addition, due to the similarities between IPD surveillance and
surveillance of other invasive bacterial diseases (such as data
elements and reporting mechanisms, and the flexibility of the
pilot platform through CNPHI) the eIPDSS could be adapted
into an omnibus invasive bacterial disease surveillance system
which would allow for robust and efficient surveillance of other
invasive bacterial diseases, such as invasive meningococcal
disease, invasive Haemophilus influenzae disease, invasive Group
A streptococcal disease and invasive Group B streptococcal
disease.
EVALUATION
Conclusion
References
The evaluation of the eIPDSS pilot project has demonstrated that
eIPDSS is a simple, timely, epi-lab linked surveillance system that
captures representative, robust information for more accurate
interpretations of IPD and antimicrobial susceptibility trends.
Ultimately, the system could help to prevent IPD by giving
explicit information on serotypes and vaccination status that
would inform policy decisions and immunization and prevention
programs.
1. European Centre for Disease Prevention and Control.
Annual epidemiological report 2013. Stockholm: ECDC;
2013.
The provincial/territorial surveillance partners have identified
some concerns during the evaluation that could be addressed by
implementing the recommendations to improve usefulness, data
quality, simplicity and acceptability and expand the surveillance
system to include four other nationally notifiable diseases. By
leveraging the flexible CNPHI platform, continued consultation
with eIPDSS surveillance partners and regular evaluations of the
system, Canada could expand, streamline and modernize its
national reporting mechanisms of invasive bacterial diseases.
Acknowledgements
This article would not have been possible without the
involvement of all federal and provincial contributors. We would
like to thank Louis-Alexandre Jalbert, Suzanne Savoie, Sophie
Wertz and Rita Raafat Gad of the New Brunswick Ministry of
Health for their expertise and input throughout the evaluation.
Conflict of interest
None.
Funding
This work was supported by the Public Health Agency of
Canada.
2. Public Health Agency of Canada. Nationally notifiable
diseases. http://dsol-smed.phac-aspc.gc.ca/dsol-smed/ndis/
list-eng.php.
3. Public Health Agency of Canada. Canadian Immunization
Guide – Pneumococcal Vaccine. Ottawa ON: PHAC; 2016.
http://www.phac-aspc.gc.ca/publicat/cig-gci/p04-pneu-eng.
php.
4. Public Health Agency of Canada. Invasive Pneumococcal
disease for health professionals. Ottawa ON: PHAC; 2016.
http://www.phac-aspc.gc.ca/im/vpd-mev/pneumococcalpneumococcie/professionals-professionnels-eng.php.
5. Demczuk WHB, Martin I, Griffith A, Lefebvre B, McGeer
A, Lovgren M, et al. Serotype distribution of invasive
Streptococcus pneumoniae in Canada after the introduction
of the 13-valent pneumococcal conjugate vaccine, 20102012. Can J Microbiol 2013 Dec; 59(12):778-788.
6. Mukhi SN, Chester TL, Klaver-Kibria JD, Nowicki DL,
Whitlock ML, Mahmud SM, et al. Innovative technology for
web-based data management during an outbreak. Online J
Public Health Inform 2011 Jun; 3(1),1-13.
7. Health Surveillance Coordinating Committee, Health
Canada. Framework and tools for evaluating health
surveillance systems. Ottawa ON: Health Canada; 2004.
8. Centers for Disease Control and Prevention. Updated
guidelines for evaluating public health surveillance systems:
Recommendations from the guidelines working group.
MMWR Recommendations and Reports 2001 July 27;50(RR13);1-35.
9. Public Health Agency of Canada. Case definitions for
communicable diseases under national surveillance. Can
Comm Dis Rep 2009;35-Suppl 2: 34-35.
10. Roush SW. Chapter 18: Surveillance indicators. In: Roush
SW, Baldy LM, eds. Manual for the surveillance of vaccinepreventable diseases. Atlanta: Centres for Disease Control
and Prevention; 2012.
CCDR • April 7, 2016 • Volume 42-4
Page 85
OUTBREAK REPORT
Outbreak of Shigella sonnei in Montréal’s
ultra-Orthodox Jewish community, 2015
Pilon PA1,2*, Camara B1, Bekal S3,4
Affiliations
Abstract
Infectious Disease and Prevention
Control, Montréal Regional Public
Health Department, Montréal, QC
1
An outbreak of Shigella sonnei that occurred in the ultra-Orthodox Jewish community (UOJC)
was the subject of an investigation and response by the Montréal Regional Public Health
Department, who collaborated with several health and community partners. A total of
27 confirmed cases were reported in this outbreak, which lasted from February to June 2015.
The epidemic curve was compatible with a point source with secondary person-to-person
transmission. In 11 of the 27 cases, pulsed-field gel electrophoresis (PFGE) analysis of strains
found a single PFGE pattern newly identified in Quebec. Almost all strains tested showed
resistance to ampicillin and trimethoprim-sulfamethoxazole (TMP/SMX). All the cases resided
in centre west Montréal. Most of the cases were under 5 years old and attended a daycare
centre, an environment recognized to be conducive to the transmission of enteric diseases. The
Montréal Regional Public Health Department sent timely information to families, daycare and
school stakeholders, community partners and synagogues in the UOJC, which helped reduce
the transmission of shigellosis in the community.
School of Public Health,
Université de Montréal, Montréal,
QC
2
Laboratoire de santé
publique du Québec,
Sainte-Anne-de-Bellevue, QC
3
Department of Microbiology
and Immunology, Université de
Montréal, Montréal, QC
4
*Correspondence: ppilon@
santepub-mtl.qc.ca
Suggested citation: Pilon PA, Camara B, Bekal S. Outbreak of Shigella sonnei in Montréal’s ultra-Orthodox
Jewish community, 2015. Can Comm Dis Rep 2016;42:86-90.
Background
On March 25, 2015, the Montréal Regional Public Health
Department detected a statistically significant space-time
cluster of 7 cases of shigellosis reported in the previous 12 days
using SaTScanTM analytical software. The first epidemiologic
investigations indicated that 3 of the 7 cases were children from
the ultra-Orthodox Jewish community (UOJC). The other 4 cases
had contracted the infection while travelling, and there were no
links between them. Prior to this cluster, on February 25,
there had been a report of a case in a daycare centre in this
community; this child’s symptoms had begun on February 19.
Based on epidemiologic and historical data, an outbreak of
shigellosis in the Montréal UOJC was strongly suspected and an
investigation was launched.
Meanwhile, in December 2014 (1), New York City issued a public
health alert regarding an outbreak involving 43 cases of Shigella
sonnei affecting two similar communities. Because members of
the UOJC regularly travel between Montréal and New York, it
was important to investigate a possible link between the
two outbreaks. The objectives of this investigation were to
further characterize the S. sonnei outbreak in the UOJC, develop
hypotheses and guide the Montréal Regional Public Health
Department’s potential interventions. An investigation report
was written to share intervention strategies and to serve as a
reference document for similar investigations.
Methodology
Case definition
A case was defined as a Montréal resident belonging to the
UOJC, with no history of recent travel abroad and with a
laboratory confirmation of S. sonnei infection, reported to the
Montréal Regional Public Health Department between
January 1 and August 31, 2015.
Case finding and data collection
Cases were identified through Quebec’s registry of notifiable
diseases. Data were collected through the registry and then by
examining case files from the epidemiologic survey. Cases were
assigned to the UOJC or an orthodox group (e.g., Belz, Satmar,
etc.) based on survey responses.
Laboratory Tests
Laboratory tests were performed in the medical microbiology
laboratories of reporting hospitals (identification of genus and
species and sensitivity profile). Identification was confirmed using
pulsed-field gel electrophoresis (PFGE) at the Laboratoire de
santé publique du Québec (LSPQ).
Epidemiologic analysis
A case list was generated and imported into Microsoft Excel
2010; the list included demographic, clinical and epidemiologic
variables. Descriptive analyses were conducted using SPSS
version 12.0.2.
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CCDR • April 7, 2016 • Volume 42-4
OUTBREAK REPORT
Public health intervention
Description of case characteristics
A survey was conducted with each family that had a reported
case. Information on prevention was provided to the family and
the appropriate daycare centre or school. Public health officials
worked with two partners within the UOJC to inform community
members through synagogues, daycare centres and schools and
to strengthen hygiene practices.
Ages ranged from 1 to 35 years; the average age was 10 years,
and the median age 4 years. Most (74%) of the cases were aged
less than 10 years and 52% aged less than 5 years) [Figure 2].
Health system partners and the Laboratoire de santé publique
du Québec were informed to increase vigilance among
health professionals and enhance surveillance and to obtain
confirmatory test results and characterization results from the
laboratory.
There were 15 (56%) males and 12 (44%) females, a 1:3 M/F
ratio. It is interesting to note that all the reported adult cases
were women, probably because women are more involved in
childcare.
Figure 2: Number of cases of the Shigella sonnei in the
ultra-Orthodox Jewish community, by age group and
sex, Montréal area, February to June 2015
Results
Case description based on time
Between February 19 and June 1, 2015, 27 confirmed cases of
S. sonnei (contracted locally) occurred in the Montréal UOJC.
This represented 79% (27/34) of all confirmed cases of S. sonnei
reported in the area for the same period. The first case was
observed on February 19, and the outbreak lasted five months.
The peak occurred in May with 10 (about 37%) reported cases.
This was followed by a decrease in June until there were no
cases in July and August. Based on the 1- to 3-day incubation
period, the case exposure period seems to have been between
February 18 and May 28, 2015. The epidemic curve (Figure 1)
was consistent with a point source with secondary
person-to-person transmission.
Case description based on environment
All the cases resided in centre west Montréal. Of the
27 cases, 11 lived within the same postal code. The
environments frequented by 23 of the 27 cases during their
infectious period were known: 8 daycare facilities for 13 cases
(57%), 3 primary schools for 5 cases (22%), their homes for
4 cases (17%) and a university for 1 case (4%). A daycare and a
school had the highest incidence with 3 cases each.
Figure 1: Epidemic curve of the Shigella sonnei
outbreak in the ultra-Orthodox Jewish community,
Montréal area, February to June 20151
Clinical presentation
Information on signs and symptoms was obtained for 22 of the
27 cases (Table 1). Fever and lower gastrointestinal symptoms
were the most common symptoms. Fever and blood in the stool,
indicating a more serious illness, occurred in 55% of the cases.
Table 1: Frequency of symptoms of Shigella sonnei in
the ultra-Orthodox Jewish community, by age group
(N=22)
Clinical
presentation
0–9 years
N=15 (%)
10–39 years
N=7 (%)
All ages
N=22 (%)
15 (100)
7 (100)
22 (100)
Cramps /
abdominal pain
14 (93)
5 (71)
19 (86)
Fever (≥38°C)
13 (86)
5 (71)
18 (82)
Blood in the
stool
10 (67)
3 (43)
13 (59)
Unusual
tiredness
9 (60)
3 (43)
12 (55)
Nausea
7 (47)
4 (57)
11 (50)
Vomiting
8 (53)
1 (14)
9 (41)
Diarrhea
Abbreviation: N, number of cases
1
The sampling date was used when the symptom onset date was missing (n=4 cases)
CCDR • April 7, 2016 • Volume 42-4
Page 87
OUTBREAK REPORT
Medical consultation and hospitalization
Potential sources of exposure
The first contact with the health care system took place at an
outpatient clinic for 24 cases (89%), and at a hospital emergency
room for 3 cases (11%). Of the 24 cases who sought medical
advice at a clinic, 18 (75%) reported to the same clinic, which
appears to serve the UOJC.
None of the 27 cases had been hospitalized or had died at the
time of the survey.
Treatment
Of the 25 cases who provided information on treatment,
17 (68%) received antibiotics; of these, 9 (53%) received
ciprofloxacin. One case received ampicillin despite the strain’s
resistance profile (Table 2).
Table 2: Types of antibiotic used to treat Shigella sonnei
infection in the ultra-Orthodox Jewish community
(N=17)
Antibiotic treatment
Number (%)1
Ciprofloxacin
9 (53)
Azithromycin
2 (12)
Cefixime
2 (12)
Cephalexin
1 (6)
Ampicillin
1 (6)
Unknown
2 (12)
Total
1
17 (100)
Of the 27 cases, 5 had a family relationship with another
confirmed case already reported to the Montréal Regional
Public Health Department. Of the 27 cases, 8 reported having
had contact with a case with diarrhea before the start of their
illness (including 3 contacts of confirmed cases). In 4 cases, the
contact was with a family member, and for the 4 other cases,
the only contact was via a daycare centre or primary school. The
index case was a 2-year-old boy who attended a daycare centre
(name not indicated), and whose symptoms began in February.
Three members of his family also had diarrhea (unknown time
sequence), but neither he nor anyone in his family had travelled
recently. The 5 cases that followed in March (4 of which had
identical pulsotypes) were also children aged between
4 and 10 years attending primary schools or different daycare
centres, but did not seem to have any clear link to the index
case. However, they were all of a similar age and could have
participated in a common activity within the UOJC, giving rise
to transmission. Of the cases that occurred in April and June,
some were siblings of earlier cases and were probably infected
through intrafamily transmission. One transmission may have
also occurred in two daycare centres (DCC A and DCC B) and a
primary school (primary school A) [initial case followed by other
cases soon after] (Table 4).
Table 4: Distribution of confirmed cases of
Shigella sonnei by exposure site (N=27)
Exposure site
Daycare centre
(N=13)
Adds up to more than 100% due to rounding
Laboratory results
All cases were laboratory confirmed by stool culture. Antibiotic
sensitivity test results were available for 24 of the 27 cases; all
were resistant to ampicillin and trimethoprim-sulfamethoxazole
(TMP/SMX) [Table 3]. In all but 2 cases (1 ciprofloxacin and
1 cefixime), we had no data on sensitivity to these antibiotics
or to azithromycin. The PFGE was performed in 11 of 27 cases,
and a single genetic profile, pulsotype 148, was highlighted. This
pulsotype, not previously identified in Quebec, was different
from the PFGE pattern of the strain that caused an outbreak in
the New York area in December 2014.
Table 3: Resistance profile of strains of Shigella sonnei
based on antibiotic sensitivity testing (N=24)
Resistance profile
Ampicillin (R) + TMP/SMX (R)
16 (67)
Ampicillin (R) + TMP/SMX (I)
6 (25)
1 (4)
TMP/SMX (I)
1 (4)
Total
24 (100)
Abbreviations: R, Resistant; I, Intermediate
Page 88
CCDR • April 7, 2016 • Volume 42-4
Number of cases
3
DCC B
2
DCC C (girls)
1
DCC D (boys)
1
DCC E
1
DCC F
1
Daycare G (girls)
1
Daycare H
1
Unknown
2
A (boys)
3
B (girls)
1
C (girls)
1
University (N=1)
A
1
Other (N=8)
Residence
4
Unknown
4
Abbreviation: DCC, daycare centre
Number (%)
Ampicillin (R)
Primary school (N=5)
Name of site
DCC A
Public health intervention
In this investigation, there was a response to each reported
case of shigellosis confirmed by the laboratory. The response
involved waiting at least 48 hours after cessation of diarrhea
before sending the child back to daycare or school. In addition,
an information sheet on the prevention of shigellosis was sent
to the parents of affected children as well as the schools and
daycares to increase the vigilance of other parents and officials in
the various settings and to strengthen preventive measures.
OUTBREAK REPORT
Discussion
Shigellosis outbreaks are cyclical within the UOJC in Montréal,
having occurred at different intensities at approximately
1- to 5-year intervals (Table 5) [2-9]. The regular recurrence of
shigellosis in the UOJC is caused by the spread of the infectious
agent as a result of travel to other similar communities with high
prevalence of the disease or through chronic carriers who serve
as a reservoir (2,5,10). The periodicity of Shigella outbreaks
in the UOJC may be due to persistent low endemicity that
generates an outbreak when a new cohort of young children with
no previous shigellosis enters daycare or school (3).
Table 5: History of Shigella sonnei outbreaks in the
ultra-Orthodox Jewish Community in the Montréal area,
1994 to 2015
Number of confirmed
cases
Period
February and June 2015
27 (pulsotype 148)
August 2011 to December 2012 (8)
38 (several pulsotypes)
November 2007 to January 2008 (7)
11 (pulsotype 35 and related
pulsotypes)
October 2004 to July 2005 (6,7)
76
July 1997 and January 1998 (6,7)
100
1994 to 1996 (2)
34 (pulsotypes 3, 3A)
The spread of shigellosis in this outbreak was caused by
intrafamily transmission (4 of the 27 confirmed cases were
siblings and several other cases had contact with family members
suffering from diarrhea) and transmission at daycare centres
(13 of the 27 cases) and school (5 of the 27 cases were
connected to a primary school). Having close contacts, attending
daycare, and having several young children at home were
considered risk factors in previously reported outbreaks (3,5).
The space-time cluster of cases and diversity of environments
suggested person-to-person transmission. The fact that cases
occurred in several groups within the UOJC supported the
argument that community environments (in addition to the family
environment) played a role in transmission. The characteristics of
the Montréal outbreak were similar to those described in other
cities (2–5). Undeveloped hygiene habits in young children and
the low infectious dose required to transmit S. sonnei diminish
the effectiveness of preventive measures in this population (3).
In the wake of outbreaks in recent years in Montréal, efforts
had been made to try to reach different groups within the
UOJC to prevent transmission of infectious diseases and, in
particular, transmission of enteric diseases. As a result of these
efforts, close ties were established with two Jewish community
organizations who deal with various groups in Montréal’s UOJC.
Through them, preventive messages from the Montréal Regional
Public Health Department were sent to those groups who have
limited contact with anyone outside their community.
As soon as the outbreak was suspected, these two Jewish
community organizations were notified and provided with
the relevant information. The first organization has a medical
clinic, a Yiddish telephone information line available to over
2,000 Jewish families, especially ultra-Orthodox groups, and
contact with the synagogues; the second organization had
counsellors in the community (daycare centre and schools).
Both organizations participated in the Montréal Regional Public
Health Department’s effort to provide timely information on
the unfolding shigellosis outbreak and the steps to prevent
and control the transmission of this disease. Posters in French,
English and Yiddish on handwashing were sent to families,
daycare centres, schools and community partners in the UOJC
to educate children and their parents and people working
at daycare centres and schools. We assume that this timely
information on preventive measures could help reduce the
transmission of shigellosis. While the outbreak appeared to
persist after March 25, preventive messages sent to the UOJC
reduced the extent of the outbreak.
The decrease in the number of cases in the epidemic curve
between April 5 and May 3 could be related to Passover
celebration that took place from April 3 to 11. The closing
of daycare centres and schools during this period reduced
transmission.
Strains of S. sonnei from confirmed cases showed resistance to
the first-line antimicrobials, ampicillin and TMP/SMX, which was
considered a serious threat in the United States by the Centers
for Disease Control and Prevention (11). This led clinicians to
make more extensive use of antimicrobials such as ciprofloxacin
or azithromycin, although some infections were already reported
to be resistant to both these antibiotics.
The PFGE pattern of strain isolated in this investigation
(pulsotype 148) showed that it had been previously unreported
in Quebec and different from the strain responsible for the
New York outbreak. Since strains of Shigella do not undergo
routine laboratory monitoring, the possibility that this strain has
been circulating for some time in Montréal or in other areas
cannot be ruled out. Laboratory monitoring of Shigella strains
could certainly facilitate epidemiologic surveillance in certain risk
groups.
This investigation has several limitations. Only cases confirmed
by laboratory analysis are identified in this report. The
information collected during case finding suggests that the
number of reported cases is lower than the true number of
cases. Some cases of diarrhea that occurred in several families
may have not been confirmed or reported to the Montréal
Regional Public Health Department. Although intrafamily
and community transmission in daycare centres and schools
is strongly suspected, the probable source of exposure was
unknown for a number of cases at the time of the survey.
Conclusion
This investigation describes an outbreak of S. sonnei in
Montréal’s UOJC that mainly affected preschool- and
school-aged children. Identifying person-to-person transmission
in a community that has limited contact with outsiders highlights
the importance of maintaining and consolidating ties with UOJC
partners to prevent outbreaks and respond quickly if they do
occur. With these partners, it is possible to work with adults
(parents, educators and teachers) to promote and strengthen
preventive measures demonstrated to be effective in the
prevention and control of infectious disease and, in particular,
Shigella outbreaks (e.g. supervising children while they wash
CCDR • April 7, 2016 • Volume 42-4
Page 89
OUTBREAK REPORT
their hands, decontaminating toys or other shared objects,
temporarily keeping children with diarrhea out of daycare
centres and schools).
Région de Montréal; 2008. 21 p (Available in French
only : http://www.santecom.qc.ca/bibliothequevirtuelle/
hyperion/9782894946985.pdf).
8. Gardhouse C. Shigellose dans la communauté juive
orthodoxe, Montréal, août 2011 – décembre 2012. Montréal
(QC): Direction de santé publique, Région de Montréal;
2013. 31 p.
Acknowledgements
We would like to thank all the investigators who worked on the
cases and dealt with families and communities; the managers
and stakeholders from the two Jewish community organizations
for their work with the UOJC; Dr. Sandra Palmieri,
Dr. Robert Allard, Maryse Lapierre and Dr. Carole Morissette for
their comments.
Conflict of interest
None.
References
1. New York City Department of Health and Mental Hygiene.
2014 Alert #39: Outbreak of shigellosis in Borough
Park and Williamsburg, December 17, 2014; [2 p.].
https://a816-health29ssl.nyc.gov/sites/NYCHAN/Lists/
AlertUpdateAdvisoryDocuments/HAN_Shigella.pdf.
2. Sobel J, Cameron DN, Ismail J, Strockbine N, Williams M,
Diaz PS, et al. A prolonged outbreak of Shigella sonnei
infections in traditionally observant Jewish communities in
North America caused by a molecularly distinct bacterial
subtype. J Infect Dis. 1998 May;177:1405-9.
3. Garrett V, Bornschlegel K, Lange D, Reddy V, Kornstein L,
Kornblum J, et al. A recurring outbreak of Shigella sonnei
among traditionally observant Jewish children in New York
City: the risks of daycare and household transmission.
Epidemiol Infect. 2006;134:1231-6.
4. Daudens E, Dejour-Salamanca D, Isnard H, Mariani-Kurkdjian
P, Filliol I, Bingen E. Épidémie de gastro-entérites aiguës à
Shigella sonnei résistantes à l’amoxicilline, au cotrimoxazole
et à l’azithromycine en Île-de-France – Janvier - Avril 2007.
Saint-Maurice (FR): Institut de veille sanitaire; 2009 Dec. 18
p. (Available in French only: www.invs.sante.fr).
5. De Schrijver K, Bertrand S, Gutierrez Garitano I, Van
den Branden D, Van Schaeren J. Outbreak of Shigella
sonnei infections in the Orthodox Jewish community of
Antwerp, Belgium, April to August 2008. Euro Surveill.
2011;16:pii=19838.
6. Andermann A. Shigellosis in the Montreal Jewish
community: review of cases and recommended control
measures. Montréal (QC): Direction de santé publique,
Région de Montréal; 2005. 35 p.
7. Hannah H. Bilan des éclosions d’infections à Shigella
sonnei, Montréal et au Québec, 5 août 2007 au 26
janvier 2008. Montréal (QC): Direction de santé publique,
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9. Susser S. Recurrent shigellosis outbreaks in the Montreal
Jewish community: case study in health inequality. Montréal
(QC): Direction de santé publique, Région de Montréal;
2012. 35 p.
10. Calderon-Margalit R, Navon-Venezia S, Gefen D, Amitai
Z, Barda R, Vulikh I, Sompolinsky D. Biennial hyperepidemic
shigellosis in an observant Jewish community. Epidemiol
Infect. 2010;138:244-52. http://www.ncbi.nlm.nih.gov/
pubmed/?term=Sompolinsky%20D%5BAuthor%5D&cauthor
=true&cauthor_uid=19602299.
11. Centers for Disease Control and Prevention. Antibiotic
resistance threats in the United States, 2013. Atlanta (GA):
CDC; 113 p. http://www.cdc.gov/drugresistance/pdf/arthreats-2013-508.pdf.
RECOMMENDATION
Interim recommendations for the reporting
of extensively drug resistant and pan-drug
resistant isolates of Enterobacteriaceae,
Pseudomonas aeruginosa, Acinetobacter
spp. and Stenotrophomonas maltophilia
German GJ1, Jamieson FB2, Gilmour M3, Almohri H4, Bullard J5, Domingo MC6, Fuller J7,
Girouard G8, Haldane D9, Hoang L10, Levett PN11, Longtin J6, Melano R2, Needle R12, Patel SN2,
Rebbapragada A13, Reyes RC14, and Mulvey MR3*
Affiliations
Note
Health PEI, Charlottetown, PEI
1
Public Health Ontario Laboratories,
Toronto, ON
2
The recommendations in this publication should be considered preliminary for one year from
the publication date. Comments regarding the document should be sent to Dr. Michael Mulvey.
All comments received will be reviewed by the Canadian Public Health Laboratory Network
Antimicrobial Resistance Subcommittee before the final recommendations are drafted and
released.
National Microbiology Laboratory,
Public Health Agency of Canada,
Winnipeg, MB
3
LifeLabs, Toronto, ON
4
Cadham Provincial Laboratory,
Winnipeg, MB
5
Laboratoire de santé
publique du Québec, INSPQ,
Ste-Anne-de-Bellevue, QC
6
Alberta Provincial Laboratory for
Public Health, Edmonton, AB
7
Centre hospitalier universitaire
Dr-Georges-L.-Dumont, Moncton, NB
8
Suggested citation: German GJ, Jamieson FB, Gilmour M, Almohri H, Bullard J, Domingo MC, Fuller J,
Girouard G, Haldane D, Hoang L, Levett PN, Longtin J, Melano R, Needle R, Patel SN, Rebbapragada A,
Reyes RC, and Mulvey MR. Interim Recommendations for the Reporting of Extensively Drug Resistant and
Pan Drug Resistant Isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp. and
Stenotrophomonas maltophilia. Can Comm Dis Rep 2016;42:91-7.
Queen Elizabeth II Health Science
Centre, Halifax, NS
9
BC Centre for Disease Control Public
Health Laboratory, Vancouver, BC
10
Saskatchewan Disease Control
Laboratory, Regina, SK
11
Newfoundland Public Health
Laboratory, St. John’s, NL
12
Dynacare, Brampton, ON
13
LifeLabs, Burnaby, BC
14
*Correspondence: Michael.
Mulvey@phac-aspc.gc.ca
1.0 Introduction
2.0 Background
These recommendations are produced under the auspices and
authority of the Canadian Public Health Laboratory Network,
Antimicrobial Resistance Working Group. They represent a
consensus of peer reviewed information and expert opinion on
the most appropriate ways to test for and report a multi-drug
resistant phenotype in common Gram-negative pathogens.
These recommendations were developed for use by all Canadian
non-veterinary clinical microbiology laboratories to provide
standardization for provincial and national surveillance programs.
Antimicrobial resistance is a growing concern for human health
as bacterial pathogens continue to accumulate genes and
genomic alterations that confer resistance to antimicrobials.
Most concerning is the occurrence of multiple resistance traits
within individual key pathogens, which greatly limits, if not
entirely eliminates the arsenal of effective treatment options
for those infections, thereby leading to poor clinical outcomes.
In Canada, we have observed these highly resistant strains in
Enterobacteriaceae, Acinetobacter spp., Stenotrophomonas
CCDR • April 7, 2016 • Volume 42-4
Page 91
RECOMMENDATION
maltophilia, and Pseudomonas aeruginosa (1-3). There is a
need for laboratories to classify organisms that are resistant to
multiple antimicrobials in order to consistently and accurately
share the information locally, nationally, and internationally with
the medical community, public health authorities and policy
makers. More specifically, classification as ‘multi-drug resistant’
is commonly an actionable finding within hospital Infection
Prevention & Control programs. Recently, there has been a
proposal to internationally standardize these definitions in
selected Gram-positive and Gram-negative organisms (4), yet
this proposal for interim definitions has not yet led to a revised
definition or national recommendations.
The goal of this document is to provide Canadian laboratories
with a framework for consistent reporting and monitoring
of multi-drug resistant organisms (MDRO), extensively drug
resistant organisms (XDRO), and pan-drug resistant organisms
(PDRO). The recommendations were based on an interim
international proposal published in 2012 for Gram-negative
organisms (4). This document modifies the following for
the Canadian setting: 1) Resistance was used instead of
non-susceptibility (Intermediate and Resistant) to better match
which antimicrobials will be clinically used for treating resistant
infections; antimicrobials that are more easily tested in the
laboratory; and those that would limit unnecessary reference
testing. 2) MDRO rules are separated for commonly used
antimicrobials in the community setting for urine infections and
non-urine infections. 3) Rather than all classes of antimicrobials
being considered in the definitions, only relevant classes that
are commonly tested in Canadian clinical laboratories were
considered. Also within a class of antimicrobials, resistance
to the most commonly used antimicrobial for treating severe
infections (i.e. meropenem or imipenem) was considered
rather than an inferior drug for infections (i.e. ertapenem for
the carbapenems). 4) Since XDRO definitions will fluctuate
from country to country based on 2nd and 3rd line available
antimicrobials, adjustments were made for antimicrobials
available/approved for use in Canada rather than all drug
categories listed in the Clinical Laboratory Standards Institute
(CLSI) (5). The justification for these modifications can be
found in Appendix 1. Over time as new antimicrobials become
available, previously available antimicrobials lose effectiveness,
or no longer available, the definitions will necessitate periodic
review. The recommendations stated herein are considered
interim and are open for stakeholder consultation such that
future recommendations evolve to accommodate public health,
community care, and acute care partners.
XDRO, and PDRO. It is understood that some laboratories
use automated methods with Food and Drug Administration
(FDA; www.fda.gov) breakpoints that may differ from the CLSI
recommendations. A laboratory using FDA breakpoints should
include the breakpoint difference in any report for MDRO,
XDRO, and PDRO.
3.3 Certain species of Enterobacteriaceae should not be tested
for particular antimicrobial agents because of intrinsic resistance
to the agent (Table 1, Exceptions).
4.0 Definitions of Screening/Testing for
MDRO, XDRO and PDRO
These interim recommendations are to be applied only to
clinical/diagnostic specimens. However, acute care and long
term care facilities, and by extension health authorities, may
choose to still apply the definitions of MDRO/XDRO/PDRO for
screening purposes as determined by their own fiscal situation
and local health resources. If isolates are part of a specialized
surveillance program (e.g. in-patient screening), it should be
clearly indicated in the laboratory report that the MDRO/XDRO/
PDRO is pertinent for colonization or carriage status only.
4.1 Enterobacteriaceae Multi-Drug Resistance Definition
It is recognized that laboratories may not test Gram-negative
isolates for all classes of antimicrobial agents and therefore
would not be able to determine MDRO, XDRO, and PDRO.
Therefore, we have included a category of multi-drug resistant
organisms (MDRO) that should be considered for screening
isolates for XDRO or PDRO.
4.1.1 There are four rules for MDRO status in Enterobacteriaceae
which takes into consideration the specific specimen type
(Table 1).
4.2 Acinetobacter spp. or Pseudomonas aeruginosa
Multi-drug Resistance Definition
4.2.1 An isolate should be considered MDRO if resistant to
THREE of the FIVE antimicrobial agents listed below (Table 2):
1. Ciprofloxacin
2. Piperacillin-tazobactam OR piperacillin
(specifically for P. aeruginosa)
3. Ceftazidime OR cefepime
4. Imipenem OR meropenem
3.0 Recommendations for Antimicrobial
Susceptibility Testing
3.1 A resistant interpretation of an isolate can be determined
using disk diffusion, broth microdilution, or agar dilution
following CLSI guidelines for the testing of Enterobacteriaceae,
Pseudomonas aeruginosa, Acinetobacter spp. and
Stenotrophomonas maltophilia (5). A Health Canada or Federal
Drug Administration (FDA) approved automated method or
gradient diffusion strips can also be used for the generation of
the antimicrobial susceptibility data.
3.2 Current CLSI breakpoints (M100) for resistance should
be used when determining the designations of MDRO,
Page 92
CCDR • April 7, 2016 • Volume 42-4
5. Tobramycin
4.3 Stenotrophomonas maltophilia Multi-Drug Resistance
Definition
4.3.1 S. maltophilia is intrinsically resistant to all carbapenems
and most cephalosporins. A clinical isolate should be considered
an MDRO if it is resistant to trimethoprim-sulfamethoxazole and
subsequent susceptibility testing indicates it is also resistant to
an oral anti-microbial (minocycline or levofloxacin) [Table 2].
RECOMMENDATION
Table 1: Rules for the determination of Multi-Drug-,
Extensively Drug-, Pan-Drug Resistant Organisms in
Enterobacteriaceae from clinical isolatesa
Rule
Speciman
1
Urine
Antimicrobial Groups
Cefixime OR
Amoxicillin-clavulanate
Ciprofloxacin
Interpretation
Resistance to
THREE of the
FOUR groups =
MDRO
(Cefixime OR
Amoxicillin-clavulanate)
Ciprofloxacin
Resistance to
THREE of the
THREE groups =
MDRO
Trimethoprim-sulfamethoxazole
3
All
Meropenemb
AND
(Ciprofloxacin
OR
Trimethoprim-sulfamethoxazole)
4
All
Tobramycin
AND
Gentamicin
AND
Piperacillin-Tazobactam
AND
(Ciprofloxacin
Resistance to
a very broad
spectrum
antimicrobial and
resistance to one
of two commonly
used and
unrelated drug
classes = MDRO
Resistance to
two commonly
susceptible
drug classes and
resistance to one
of two commonly
used and
unrelated drug
classes = MDRO
OR
All
Tobramycin AND Gentamicin
Piperacillin-Tazobactam
Imipenem OR Meropenem
Cefepime OR (cefotaxime/
ceftriaxone) AND ceftazidime
Resistance to
FOUR of
the SIX
antimicrobial
groups = XDRO
Same groups listed in rule #5
6. Trimethoprim-sulfamethoxazole
5.2 Pseudomonas aeruginosa XDRO Definition
5.2.1 A P. aeruginosa should be considered an XDRO when the
isolate is resistant to FOUR of the SIX antimicrobial agents listed
below (Table 2):
1. Tobramycin
2. Piperacillin OR piperacillin-tazobactam
3. Imipenem OR meropenem OR doripenem
4. Cefepime OR ceftazidime
5. Ciprofloxacin
6. Colistin
5.2.2 A P. aeruginosa should be considered a PDRO when the
isolate is resistant to ALL of the antimicrobial agents listed in
5.2.1.
5.3.1 An Acinetobacter spp. should be considered an XDRO
when the isolate is resistant to SIX of the EIGHT antimicrobial
agents listed below (Table 2):
1. Gentamicin OR Tobramycin
3. Imipenem OR meropenem OR doripenem
Trimethoprim-Sulfamethoxazole
All
3. Imipenem OR meropenem
2. Piperacillin-tazobactam
Ciprofloxacin
6
2. Piperacillin-tazobactam
5.3 Acinetobacter spp. XDRO Definition
Trimethoprim-sulfamethoxazole)
5
1. Tobramycin AND gentamicin
5. Ciprofloxacin
Nitrofurantoin
Non-Urine
5.1.3 An isolate of Enterobacteriaceae should be considered
an XDRO when the isolate is resistant to FOUR of the SIX
antimicrobial agents listed below (Table 1):
4. Cefepime OR (cefotaxime/ceftriaxone) AND ceftazidime
Trimethoprim-Sulfamethoxazole
2
5.1.2 Unlike the definition of MDRO for Enterobacteriaceae,
the type of specimen does not need to be considered for the
definition of XDRO.
Resistance
to SIX of SIX
antimicrobial
groups = PDRO
Abbreviations: MDRO, multi-drug resistant organisms; XDRO, extensively drug
resistant organisms; PDRO, pan-drug resistant organisms
a
Expert rules modified from Leclercq et al., 2013 (7)
b
Imipenem can be substituted for meropenem with the exception of Proteus spp.
5.0 Confirmation of XDRO
5.1 Enterobacteriaceae XDRO Definition
5.1.1 An isolate that has been determined to be an MDRO
should be considered an XDRO by testing/assessing resistance
to other antimicrobial agents listed in this section.
4. Cefepime OR ceftazidime
5. Ciprofloxacin
6. Colistin
7. Doxycycline OR minocycline
8. Trimethoprim-sulfamethoxazole (note: intrinsically
resistant to trimethoprim)
5.4 Stenotrophomonas maltophilia XDRO Definition
A S. maltophilia should be considered an XDRO if resistant
to three oral antimicrobials (trimethoprim-sulfamethoxazole,
minocycline, and levofloxacin). The isolate should be referred for
complete antimicrobial susceptibility testing to exclude a PDRO
(see Table 2).
CCDR • April 7, 2016 • Volume 42-4
Page 93
RECOMMENDATION
6.0 Confirmation of PDRO
2. Gender of patient
An Enterobacteriaceae, P. aeruginosa, Acinetobacter spp.
should be considered a PDRO when the isolate is resistant
to ALL antimicrobial agents listed in Table 1 (rule 6),
section 5.2.1, or 5.3.1, respectively. S. maltophilia should be
considered a PDRO if it is resistant to all of the following:
trimethoprim-sulfamethoxazole, levofloxacin, ceftazidime, and
chloramphenicol.
3. Type of clinical specimen (blood, respiratory, skin/soft
tissue, or urine)
4. Date of collection
5. Antimicrobial susceptibility testing results from submitting
laboratory
7.0 Reporting to Reference Laboratories
7.1 Any laboratory identifying a MDRO that cannot confirm an
XDRO or PDRO using additional antimicrobial susceptibility tests
should send the isolate to a reference (provincial) laboratory
(See Appendix 2).
7.2 The reference (provincial) laboratory should be notified of
any XDR or PDR organisms identified and the isolate should be
forwarded to the reference laboratory, and should include the
following information:
1. Age of patient
6. Out of Canada travel history in the last 3 months. Travel
history is dated from the time of the first isolation of the
organism. This is highly recommended for inpatients and
desirable for outpatients. All countries traveled should be
listed.
7.3 If multiple clinical isolates of the same species and
susceptibility pattern are recovered from the same patient, send
the isolate from the most invasive site where possible. Additional
isolates of the same species and susceptibility pattern should
be reported/sent to a reference laboratory no more frequently
than every 7 days after the first isolate. Annotating as an MDRO/
XDRO/PDRO on the clinical report should continue for each
isolate regardless number of isolates or time interval between
specimens.
Table 2: Definitions for the determination of Multi-Drug-, Extensively Drug-, Pan-Drug Resistant Organisms in
select organisms
MDRO
Definition
XDRO / PDRO
Antimicrobial Groups
Definitions
Antimicrobial Groups
Organism: Pseudomonas aeruginosa
Resistance to
THREE of the FIVE
antimicrobial groups
Ciprofloxacin
Piperacillin-tazobactam OR piperacillin
Ceftazidime OR cefepime
Resistance to FOUR of the SIX
antimicrobial groups = XDRO
Resistance to SIX of the SIX
antimicrobial groups = PDRO
Imipenem OR meropenem
Tobramycin
Tobramycin
Piperacillin-tazobactam OR piperacillin
Imipenem OR meropenem OR
doripenem
Cefepime OR ceftazidime
Ciprofloxacin
Colistin
Organism: Acinetobacter spp.
Resistance to
THREE of the FIVE
antimicrobial groups
Ciprofloxacin
Piperacillin-tazobactam
Ceftazidime OR cefepime
Resistance to SIX of the EIGHT
antimicrobial groups = XDRO
Gentamicin OR tobramycin
Resistance to all groups = PDRO
Piperacillin-tazobactam
Imipenem OR meropenem
Imipenem OR meropenem OR
doripenem
Tobramycin
Cefepime OR ceftazidime
Ciprofloxacin
Colistin
Doxycycline OR minocycline
Trimethoprim-sulfamethoxazole
Organism: Stenotrophomonas maltophilia
Resistance to BOTH
antimicrobial groups
Trimethoprim-sulfamethoxazole
Minocycline OR levofloxacin
Resistance to the FIRST THREE
antimicrobial groups = XDRO
Resistance to all antimicrobial
groups = PDRO
Trimethoprim-sulfamethoxazole
Minocycline
Levofloxacin
Ceftazidime
Chloramphenicol
Abbreviations: MRDO, multi-drug resistant organsims; XDRO, extensively drug resistant organisms; PDRO, pan-drug resistant organisms
Page 94
CCDR • April 7, 2016 • Volume 42-4
RECOMMENDATION
7.4 It is suggested that reports of clinical specimens found to
contain XDRO or PDRO isolates incorporate the term Extensively
Drug Resistant Organism or Pan-Drug Resistant Organism within
the body of the clinical report.
7.5 Any XDRO or PDRO isolate identified should be reported
to public health according to local, regional, and provincial
regulations with the additional information outlined in 7.2.
7.6 The originating laboratory should retain the XDRO or PDRO
isolates for at least six months, or as required by provincial or
local regulations.
7.7 The reference (provincial) laboratory should report all of the
data to the National Microbiology Laboratory as defined in 7.2.
Acknowledgements
The subcommittee would like to acknowledge the work of
Dr. John Conly (University of Alberta), Dr. Charles Frenette
(McGill University), and all the other members of the Canadian
Infectious Disease Steering Committee Antimicrobial Resistance
Surveillance Task Group. We also appreciate the support of
Dr. George Zhanel (University of Manitoba) of the Canadian
Antimicrobial Resistance Alliance for feedback on earlier versions
of the document. We thank members of the Canadian Public
Health Laboratory Network Laboratory Director’s Council for
review and final approval of the document. We would also like
to thank Ms. Sandra Radons-Arneson from our secretariat for her
support.
2. Mataseje LF, Bryce E, Roscoe D, Boyd DA, Embree J, Gravel
D, Katz K, Kibsey P, Kuhn M, Mounchili A, Simor A, Taylor G,
Thomas E, Turgeon N, Mulvey MR, Canadian Nosocomial
Infection Surveillance Program. 2012. Carbapenem-resistant
Gram-negative bacilli in Canada 2009-10: results from
the Canadian Nosocomial Infection Surveillance Program
(CNISP). J Antimicrob Chemother 67:1359–1367.
3. Tien HC, Battad A, Bryce EA, Fuller J, Mulvey M, Bernard K,
Brisebois R, Doucet JJ, Rizoli SB, Fowler R, Simor A. 2007.
Multi-drug resistant Acinetobacter infections in critically
injured Canadian forces soldiers. BMC Infect Dis 7:95-2000.
4. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas
ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, OlssonLiljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ,
Vatopoulos A, Weber JT, Monnet DL. 2012. Multidrugresistant, extensively drug-resistant and pandrug-resistant
bacteria: an international expert proposal for interim
standard definitions for acquired resistance. Clin Microbiol
Infect 18:268-281.
5. Clinical and Laboratory Standards Institute. Performance
Standards for Antimicrobial Susceptibility Testing: TwentyThird Informational Supplement M100-S25. CLSI, Wayne,
PA, USA, 2015.
6. Mosby’s Medical Dictionary 9th ed 2012 St. Louis, MO:
Mosby Elsevier.
7. Leclercq R, Canton R, Brown DFJ, Giske CG, Heisig P,
MacGowan AP, Mouton JW, Nordmann P, Rodloff AC,
Rossolini GM, Soussy CJ, Steinbakk M, Winstanley TG,
Kahlmeter G. 2013. EUCAST expert rules in antimicrobial
susceptibility testing. Clin Microbiol Infect 19:141–160.
Conflict of interest
None.
Funding
This work was supported in kind by all laboratories of the
authors and the Canadian Public Health Laboratory Network
Antimicrobial Resistance Subcommittee.
References
1. Laupland KB, Parkins MD, Church DL, Gregson DB, Louie TJ,
Conly JM, Elsayed S, Pitout JDD. 2005. Population-based
epidemiological study of infections caused by carbapenemresistant Pseudomonas aeruginosa in the Calgary Health
Region: importance of metallo-beta-lactamase (MBL)producing strains. J Infect Dis 192:1606–1612.
CCDR • April 7, 2016 • Volume 42-4
Page 95
RECOMMENDATION
Appendix 1
Methodology for Developing the Recommendations
The article published by Magiorakos and colleagues (2012)
was used as the main reference for the development of
these Canadian recommendations. Drs. German and Mulvey
developed the initial framework for the document, which
was reviewed by the Canadian Public Health Laboratory
Network (CPHLN) AMR Working Group members and invited
collaborators. Two main considerations were discussed by the
working group members: (i) formulation of a recommendation
that focused on antimicrobial drugs commonly used in Canada;
and (ii) creation of a document that is easy to use by frontline
laboratories, which predominantly utilize automated methods for
generating antimicrobial susceptibility data.
Three rounds of discussion and document revision took
place with the working group. This included discussion
and suggestions from the Communicable and Infectious
Disease Steering Committee (CIDSC) AMR Task Group from
the Pan-Canadian Public Health Network. The final draft
recommendations were reviewed by the CPHLN Executive.
Major variation with recommendations in this document as
compared to Magiorakos et. al. (2012) was as follows:
1. The working group decided to focus on Gram-negative
isolates to keep the recommendations straightforward
and achievable. It was decided that recommendations for
Gram-positive organisms would be addressed in a future
document;
2. Stenotrophomonas maltophilia was added as an additional
Gram-negative organism to be considered for the reporting
of MDRO, XDRO and PDRO in the Canadian document;
3. Although the definition of MDRO in Gram-negative
organisms is an important consideration, given the
treatment complications that can be associated with these
infections, it was decided at a provincial and national level
to voluntarily report only XDRO and PDRO isolates and use
the identification of an MDRO as a screening test to direct
further testing and reporting of resistant isolates. This was
done to ensure frontline laboratories could easily report
their findings to reference laboratories, or request additional
tests of antimicrobial drugs not covered under the frontline
antimicrobial drug panel needed to confirm XDRO/PDRO.
Page 96
CCDR • April 7, 2016 • Volume 42-4
4. A great deal of discussion focused on the value of using the
definition of resistance, as defined by CLSI (2015), rather
than that of non-susceptibility proposed by Magiorakos
et. al. (2012). It was decided to use the CLSI definition of
resistance based on the main arguments put forward, which
were: (i) front-line laboratories may have difficulty analyzing
‘intermediate resistance’ data in the context of MDRO/
XDRO/PDRO; (ii) there were concerns about the reporting
of these organisms in relation to public health. A stringent
definition of resistance was determined to be the most
feasible solution.
5. It was noted that laboratories may have to use FDA
breakpoints, which may differ from the CLSI definitions.
It was requested in the recommendations that these
differences be noted in the report to the reference
laboratory.
6. The exhaustive antimicrobial agents listed in the Tables
of the Magiorakos et. al. (2012) publication was simplified
to reflect the antimicrobial agents commonly used and
available in Canada.
7. Ertapenem was removed as a marker for carbapenem
resistance in Enterobacteriaceae. The specificity of
ertapennem is lower than that of meropenem and imipenem
and is not commonly used in a clinical laboratory setting.
8. With the exception of Acinetobacter spp. and S. maltophilia,
the tetracyclines were removed from the list of antimicrobials
to be considered as they are not frequently tested in
frontline laboratories nor are they commonly used to treat
serious infections.
9. The Canadian recommendations requested additional
clinical information that were not included in the Magiorakos
et. al. (2012) publication.
RECOMMENDATION
Appendix 2
Reference Laboratory Contact Information
Dr. Linda Hoang
BC Public Health Microbiology & Reference Laboratory,
655 West 12th Avenue,
Vancouver, BC, V5Z 4R4
linda.hoang@bccdc.ca
Dr. Gabriel Girouard
Centre Hospitalier Universitaire Dr-Georges-L-Dumont,
330 Avenue Universite,
Moncton, NB, E1C 2Z3
gabriel.girouard@vitalitenb.ca
Dr. Jeff Fuller
Alberta Provincial Laboratory for Public Health,
Alberta Health Services,
2B3.13 WMC, 8440-112 Street,
Edmonton, AB, T6G 2J2
jeff.fuller@albertahealthservices.ca
Dr. David Haldane
Queen Elizabeth II Health Science Centre,
5788 University Avenue,
Halifax, NS, B3H 1V8
david.haldane@cdha.nshealth.ca
Dr. Paul Levett
Saskatchewan Disease Control Laboratory,
5 Research Drive,
Regina, SK, S4S 0A4
plevett@health.gov.sk.ca
Dr. Greg German
Queen Elizabeth Hospital
60 Riverside Drive
Charlottetown, PE C1A 8T5
gjgerman@ihis.org
Dr. Jared Bullard
Cadham Provincial Laboratory,
750 William Avenue,
Winnipeg, MB, R3E 3J7
jared.bullard@gov.mb.ca
Robert Needle
Newfoundland Public Health Laboratory,
Dr. L.A. Miller Centre,
100 Forest Road,
St. John’s, NL, A1A 3Z9
robert.needle@easternhealth.ca
Dr. Samir Patel
Public Health Ontario Laboratories,
661 University Avenue, Ste. 1701
Toronto, ON, N5G 1M1
samir.patel@oahpp.ca
Dr. Michael Mulvey
National Microbiology Laboratory
1015 Arlington Street
Winnipeg, MB, R3E 3R2
michael.mulvey@phac-aspc.gc.ca
Dr. Brigitte Lefebvre
Laboratoire de santé publique du Québec,
Institut national de santé publique du Québec,
20045 chemin Sainte-Marie,
Ste-Anne-de-Bellevue (Québec) H9X 3R5
marc-christian.domingo@inspq.qc.ca
CCDR • April 7, 2016 • Volume 42-4
Page 97
ID NEWS
Efficacy and safety of RTS,
S/AS01 malaria vaccine
The RTS,S/AS01 vaccine
continues to show modest
protection
Source: RTS,S Clinical Trials Partnership. Efficacy and safety of
RTS,S/AS01 malaria vaccine with or without a booster dose in infants
and children in Africa: final results of a phase 3, individually randomised,
controlled trial. Lancet. 2015 Jul 4;386(9988):31-45. doi: 10.1016/S01406736(15)60721-8. Epub 2015 Apr 23.
Source: Rosenthal PJ. The RTS,S/AS01 vaccine continues to
show modest protection against malaria in African infants
and children (Commentary). Evid Based Med 2015;20:179
doi:10.1136/ebmed-2015-110231.
BACKGROUND: The efficacy and safety of the RTS,S/AS01 candidate
malaria vaccine during 18 months of follow-up have been published
previously. Herein, we report the final results from the same trial, including
the efficacy of a booster dose.
Malaria remains one of the greatest infectious burdens in the
world. The RTS,S vaccine results from decades of research
showing that human responses to the Plasmodium falciparum
circumsporozoite protein can protect against malaria. Vaccine
developments benefitted from adjuvant optimisation, with AS01
chosen for recent trials. RTS, S has been extensively studied in
African children, with vaccine efficacy approximately 25–50%
against both symptomatic and severe malaria, but efficacy
lower in infants than in children and waning over time after
immunization.
METHODS: From March 27, 2009, until Jan 31, 2011, children (age 5-17
months) and young infants (age 6-12 weeks) were enrolled at 11 centres in
seven countries in sub-Saharan Africa. Participants were randomly assigned
(1:1:1) at first vaccination by block randomisation with minimisation by
centre to receive three doses of RTS,S/AS01 at months 0, 1, and 2 and a
booster dose at month 20 (R3R group); three doses of RTS,S/AS01 and
a dose of comparator vaccine at month 20 (R3C group); or a comparator
vaccine at months 0, 1, 2, and 20 (C3C [control group]). Participants were
followed up until Jan 31, 2014. Cases of clinical and severe malaria were
captured through passive case detection. Serious adverse events (SAEs)
were recorded. Analyses were by modified intention to treat and per
protocol. The coprimary endpoints were the occurrence of malaria over
12 months after dose 3 in each age category. In this final analysis, we
present data for the efficacy of the booster on the occurrence of malaria.
Vaccine efficacy (VE) against clinical malaria was analysed by negative
binomial regression and against severe malaria by relative risk reduction.
This trial is registered with ClinicalTrials.gov, number NCT00866619.
FINDINGS: 8922 children and 6537 young infants were included in the
modified intention-to-treat analyses. Children were followed up for a
median of 48 months (IQR 39-50) and young infants for 38 months (34-41)
after dose 1. From month 0 until study end, compared with 9585 episodes
of clinical malaria that met the primary case definition in children in the
C3C group, 6616 episodes occurred in the R3R group (VE 36·3%, 95%
CI 31·8-40·5) and 7396 occurred in the R3C group (28·3%, 23·3-32·9);
compared with 171 children who experienced at least one episode of
severe malaria in the C3C group, 116 children experienced at least one
episode of severe malaria in the R3R group (32·2%, 13·7 to 46·9) and
169 in the R3C group (1·1%, -23·0 to 20·5). In young infants, compared
with 6170 episodes of clinical malaria that met the primary case definition
in the C3C group, 4993 episodes occurred in the R3R group (VE 25·9%,
95% CI 19·9-31·5) and 5444 occurred in the R3C group (18·3%, 11·7-24·4);
and compared with 116 infants who experienced at least one episode
of severe malaria in the C3C group, 96 infants experienced at least one
episode of severe malaria in the R3R group (17·3%, 95% CI -9·4 to 37·5)
and 104 in the R3C group (10·3%, -17·9 to 31·8). In children, 1774 cases of
clinical malaria were averted per 1000 children (95% CI 1387-2186) in the
R3R group and 1363 per 1000 children (995-1797) in the R3C group. The
numbers of cases averted per 1000 young infants were 983 (95% CI 5921337) in the R3R group and 558 (158-926) in the R3C group. The frequency
of SAEs overall was balanced between groups. However, meningitis was
reported as a SAE in 22 children: 11 in the R3R group, ten in the R3C
group, and one in the C3C group. The incidence of generalised convulsive
seizures within 7 days of RTS,S/AS01 booster was 2·2 per 1000 doses in
young infants and 2·5 per 1000 doses in children.
INTERPRETATION: RTS,S/AS01 prevented a substantial number of cases of
clinical malaria over a 3-4 year period in young infants and children when
administered with or without a booster dose. Efficacy was enhanced by the
administration of a booster dose in both age categories. Thus, the vaccine
has the potential to make a substantial contribution to malaria control
when used in combination with other effective control measures, especially
in areas of high transmission.
Page 98
CCDR • April 7, 2016 • Volume 42-4
ID NEWS
Evaluation of anthrax vaccine
safety in 18-20 year olds
Single dose tetravalent dengue
vaccine
Source: King JC Jr, Gao Y, Quinn CP, Dreier TM, Vianney C,
Espeland EM. Evaluation of anthrax vaccine safety in 18 to 20
year olds: A first step towards age de-escalation studies in
adolescents. Vaccine. 2015 May 15;33(21):2470-6. doi: 10.1016/j.
vaccine.2015.03.071. Epub 2015 Apr 5.
Source: Durbin AP, Kirkpatrick BD, Pierce KK, Carmolli MP, Tibery
CM, Grier PL, et al. A 12-month interval dosing study in adults
indicates that a single dose of the NIAID tetravalent dengue
vaccine induces a robust neutralizing antibody response. J
Infect Dis. 2016 Feb 16. pii: jiw067.
BACKGROUND/OBJECTIVES: Anthrax vaccine adsorbed (AVA,
BioThrax(®)) is recommended for post-exposure prophylaxis
administration for the US population in response to large-scale
Bacillus anthracis spore exposure. However, no information
exists on AVA use in children and ethical barriers exist to
performing pre-event pediatric AVA studies. A Presidential Ethics
Commission proposed a potential pathway for such studies
utilizing an age de-escalation process comparing safety and
immunogenicity data from 18 to 20 year-olds to older adults and
if acceptable proceeding to evaluations in younger adolescents.
We conducted exploratory summary re-analyses of existing
databases from 18 to 20 year-olds (n=74) compared to adults
aged 21 to 29 years (n=243) who participated in four previous
US government funded AVA studies.
The ideal dengue vaccine will provide protection against
all serotypes of dengue virus and will be economical and
uncomplicated in its administration. To determine the ability of a
single dose of live-attenuated tetravalent dengue vaccine TV003
to induce a suitable neutralizing antibody response, a
placebo-controlled clinical trial was performed in 48 healthy
adults who received two doses of vaccine or placebo
administered 12 months apart. Evaluation of safety, vaccine
viremia, and neutralizing antibody response after each dose
indicated that the first dose of vaccine was capable of preventing
infection with the second dose, thus indicating that multiple
doses are unnecessary.
METHODS: Data extracted from studies included elicited local
injection-site and systemic adverse events (AEs) following AVA
doses given subcutaneously at 0, 2, and 4 weeks. Additionally,
proportions of subjects with ≥4-fold antibody rises from baseline
to post-second and post-third AVA doses (seroresponse) were
obtained.
RESULTS: Rates of any elicited local AEs were not significantly
different between younger and older age groups for local events
(79.2% vs. 83.8%, P=0.120) or systemic events (45.4% vs.
50.5%, P=0.188). Robust and similar proportions of
seroresponses to vaccination were observed in both age groups.
CONCLUSIONS: AVA was safe and immunogenic in
18 to 20 year-olds compared to 21 to 29 year-olds. These results
provide initial information to anthrax and pediatric specialists if
AVA studies in adolescents are required.
CCDR • April 7, 2016 • Volume 42-4
Page 99
LINKS
Upcoming
April 18–20, 2016. 19th Annual Conference on Vaccine
Research. Baltimore, MD, USA. http://www.cvent.com/
events/19th-annual-conference-on-vaccine-research/
event-summary-9c2a6b5301a64921afbd9c07a4cffa14.
aspx?refid=spcoc
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July 18–22, 2016. 21st International AIDS Conference (AIDS
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Page 100
CCDR • April 7, 2016 • Volume 42-4
CCDR
CANADA
COMMUNICABLE
DISEASE REPORT
Public Health Agency of Canada
130 Colonnade Road
Address Locator 6503B
Ottawa, Ontario K1A 0K9
ccdr-rmtc@phac-aspc.gc.ca
To promote and protect the health of Canadians
through leadership, partnership, innovation and action
in public health.
Public Health Agency of Canada
Published by authority of the Minister of Health.
© Her Majesty the Queen in Right of Canada,
represented by the Minister of Health, 2016
This publication is also available online at
http://www.phac-aspc.gc.ca/publicat/ccdrrmtc/16vol42/index-eng.php
Également disponible en français sous le titre :
Relevé des maladies transmissibles au Canada
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