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Epidemiology and Infection
Chemoprophylaxis and vaccination in preventing subsequent cases of meningococcal
disease among households contacts of a case of meningococcal disease: a systematic
review
L. Telisinghe, T. D. Waite, M. Gobin, O. Ronveaux, K. Fernandez, J. M. Stuart, R. J. P. M.
Scholten
Supplementary material
Supplementary Table S1: Study design features for assessing the risk of bias in cohort studies (based on the
Newcastle-Ottawa Scalel(1))
Study number
Author
Year
Was there a comparison:
Between two or more groups/ groups of participants receiving different
interventions?
Within the same group/ group of participants over time?
Were groups/participants allocated to intervention groups by:
Time difference? (i.e. groups not concurrently followed-up)
Location differences?
Treatment decisions specific to an area?
Participants' or groups preferences?
Some other process? (specify)
Which parts of the study were prospective:
Identification of participants/groups?
Assessment of baseline and allocation to intervention?
Assessment of outcomes?
Generation of hypotheses?
Representativeness of the exposed cohort of all household contacts of a
case of meningococcal disease
Yes
Somewhat
Not representative (selected group of household contacts)
No description
Selection of non-exposed cohort
From the same community as exposed cohort
Drawn from a different source
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__________________
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No description
Ascertainment of exposure
Objective source
Self-report
No description
Demonstrated that outcome was not present at the start
Yes
No
On what variables was comparability between groups assessed:
Potential confounders?
Baseline assessment of outcome variables?
Assessing the outcome
Independent blind assessment
Record linkage
Self-report
No description
Was follow-up long enough for the outcome to occur
Yes
No
Adequacy of cohort follow-up
Complete follow-up
Subjects lost to follow-up unlikely to introduce bias - >70% followed up
Successful follow-up <70%
No description
Was there adequate control for confounding?
Yes
No
No description
Y=Yes; P=Possibly; P*=Possible for one group only; N=No; na=not applicable. NB:. Note that ‘possibly’ is used in the table to indicate
cells where either ‘Y’ or ‘N’ may be the case. It should not be used as a response option when applying the checklist; if uncertain, the
response should be ‘can’t tell
Supplementary Table S2: Chemoprophylaxis – risk of bias assessment for observational studies
Item
Stefanoff 2008(2)
Samuelsson 2000(3)
Scholten 1993(4)
MDSG 1976(5)
Kristiansen 1992(6)
Cohort
Cohort
Cohort
Cohort
Cohort (time series in
(national)
(national)
(national)
Treatment decision
Treatment decision
Treatment decision
Treatment decision
Treatment decision
specific to area
specific to area
specific to area
specific to area
specific to area
+
-
+
+
+
+
+
+
+
-
Comparability of exposed and unexposed assessed
-
-
-
-
-
Baseline demographic details given
-
-
-
-
-
Study design
Allocation of intervention
one county)
Selection
Cohort exposed representative of all household contacts
of a case of meningococcal disease
Cohort not given chemoprophylaxis from the same
population as the exposed cohort
Comparator group from a
different time period to
Comments
Fatal cases excluded
intervention group but from
the same area.
Outcomes
Objective sources used to ascertain outcome
+
?
+
-
+
Adequate duration of follow up for outcome
ascertainment
Losses to follow up/no information
?
?
+
+
+
?
32%
25%
?
?
Households contacted to
Follow up 7-31months
378/502 eligible households
enquire on secondary cases,
during the intervention
included. Valid information
at least 30days after
period. From 1984-1987
only on 1102/1130 (97.5%) of
hospitalization of index case.
(comparator period) some
included contacts.
No information to assess
cases were followed up for
losses to follow-up
at least 300 days.
-
-
Notification systems used to
identify cases. Households
Data obtained from
Comments
author
interviewed. Unclear if
subsequent cases determined by
notification or interview.
172/252 eligible households
participated
Analysis
Adequate control for confounders
MDSG = meningococcal disease surveillance group
-
-
-
Supplementary Table S3: Chemoprophylaxis – risk of bias assessment for the randomised controlled trial (Kaiser 1974(7))
Domain
Judgement
Justification
Selection bias
Random sequence generation
Allocation concealment
Low risk of bias
Unclear risk of bias
Allocation by dice throw
Not stated
Performance bias
Blinding
Low
Not specified, but it is unlikely that
blinding would have influenced
the outcome.
Detection bias
Blinding of outcome assessment
Low
Unclear if investigators assessing
outcome status of study
participants were blinded.
However, it is unlikely that
assessment of this objective
outcome would have been
influenced (and there were no
subsequent cases in the study)
Attrition bias
Incomplete outcome data
Unclear risk of bias
Not stated
Unclear risk of bias
Protocol not available to
Reporting bias
Selective reporting
determine main objectives of
study
Supplementary Figure S1: Timings of all cases of invasive meningococcal disease among household contacts of an index case
5
Cases of IMD in the first 24 hours following the index case
Cases of IMD in the control arm
Cases of IMD in the intervention arm
Number of cases
4
3
2
1
0
Days
Supplementary Figure S2: Forest plot of the risk of subsequent cases of meningococcal disease in the one year after an index case among
household contacts given and not given chemoprophylaxis
Risk
Events,
Events,
%
name
Ratio (95% CI)
Treatment
Control
Weight
stefanoff
0.68 (0.07, 6.49)
1/629
3/1276
23.23
samuelsson
0.02 (0.00, 0.42)
0/724
2/72
53.27
Scholten
0.75 (0.08, 6.67)
1/276
4/826
23.50
Overall (I-squared = 52.4%, p = 0.122)
0.34 (0.11, 1.06)
2/1629
9/2174
100.00
.001
.01
.11
.34
Favours chemoprophylaxis
1
2
6
Favours no chemoprophylaxis
Risk Ratio
Supplementary Table S4: Vaccination – risk of bias assessment for the randomised
controlled trial (Greenwood 1978(8))
Domain
Judgement
Justification
Selection bias
Random sequence generation
Unclear risk of bias
Alternative compounds allocated
to intervention and comparator
group. Unclear if allocation could
have been predicted in advance
Allocation concealment
Unclear risk of bias
Not specified
Performance bias
Blinding
Low
Not specified, but it is unlikely that
blinding would have influenced
the outcome.
Detection bias
Blinding of outcome assessment
Low / Unclear risk of bias
Unclear if investigators assessing
outcome status of study
participants were blinded.
However it is unlikely that blinding
would influence the outcome
assessment for definite cases.
For probable cases, the risk of
bias is unclear
Attrition bias
Incomplete outcome data
Low risk of bias
Study does not appear to have
any missing data for outcomes
Reporting bias
Selective reporting
Unclear risk of bias
Protocol not available to
determine main objectives of
study
References
1.
Wells GA, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of
nonrandomised studies in meta-analyses. . Available from:
http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm
2.
Stefanoff P, et al. The detection of meningococcal household clusters and their prophylaxis
in the changing epidemiological situation of invasive meningococcal disease in Poland, 2003-2006.
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable
disease bulletin. 2008;13(10).
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Samuelsson S, et al. Prevention of secondary cases of meningococcal disease in Denmark.
Epidemiology and infection. 2000;124(3):433-40.
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Kristiansen BE, et al. Preventing secondary cases of meningococcal disease by identifying
and eradicating disease-causing strains in close contacts of patients. Scandinavian journal of
infectious diseases. 1992;24(2):165-73.
7.
Kaiser AB, et al. Seroepidemiology and chemoprophylaxis disease due to sulfonamideresistant Neisseria meningitidis in a civillian population. The Journal of infectious diseases.
1974;130(3):217-24.
8.
Greenwood BM, et al. Prevention of secondary cases of meningococcal disease in household
contacts by vaccination. British medical journal. 1978;1(6123):1317-9.