Original Studies
Recurrent Pneumococcal Meningitis in Children
A Multicenter Case–control Study
Laura Darmaun, MD,* Corinne Levy, MD, PhD,†‡§¶ Marion Lagrée, MD,*‡ Stéphane Béchet, MSc,†§¶
Emmanuelle Varon, MD,‡║ Rodrigue Dessein, MD, PhD,** Robert Cohen, MD,†‡§¶‡‡ Alain Martinot,
MD,*‡†† and François Dubos, MD, PhD*‡††; for the ACTIV-GPIP Study Group
Background: Pneumococcal meningitis (PM) is a serious disease that can
rarely recur at a later time after the initial episode.
Methods: A retrospective multicenter case–control study was conducted
with data for children 18 years of age or younger obtained from the National
Observatory of Bacterial Meningitis in Children between January 2001 and
September 2015. Cases were all patients with RPM. Each case was matched
with 2 randomized controls with a single PM episode in the year of the first
episode of PM in the case and born the same year. Case and control data
were compared.
Results: Among the 1634 PM episodes in children 18 years of age or
younger, 24 (1.5%) children had RPM. RPM cases were significantly less
frequent than single PM cases in winter (27% vs. 48%; P=0.03) and showed
significantly less concomitant ear, nose and throat infections when consid-
ering the first episode (30% vs. 56%, P = 0.04) and all episodes (28% vs.
56%, P < 0.01). Cerebrospinal fluid leakage was frequent in RPM cases
versus controls (83% vs. 10%, P < 0.01), including 25% discovered after
the third PM episode. Immune deficiency was absent in cases and present
in 15% of controls. Cases and controls did not differ in death rate or neu-
rologic outcome.
Conclusions: RPM is rare in children. Cerebrospinal fluid leakage must
be considered.
Key Words: Streptococcus pneumoniae, children, recurrent meningitis,
case–control study
(Pediatr Infect Dis J 2019;38:881–886)
Accepted for publication March 14, 2019.
From the *CHU Lille, Urgences pédiatriques & maladies infectieuses, Lille,
France; †ACTIV (Association Clinique et Thérapeutique Infantile du Val
de Marne), Saint Maur-des-Fossés, France; ‡GPIP, Groupe de Pathologies
infectieuses Pédiatriques, Paris, France; §Université Paris Est, IMRB-GRC
GEMINI, Créteil, France; ¶Clinical Research Center (CRC), Centre Hospit-
alier Intercommunal de Créteil, Créteil, France; ║National Reference Center
for Pneumococci, Laboratoire de Microbiologie, Assistance Publique-Hôpi-
taux de Paris, Hôpital Européen Georges-Pompidou, Paris, France; **Uni-
versity of Lille, CHU Lille, Service de Bactériologie and ††University of
Lille, EA2694: Santé Publique, Épidémiologie & Qualité des Soins, CHU
Lille, University Lille, Lille, France; and ‡‡Unité Court Séjour, Petits nour-
rissons, Service de Néonatalogie, Centre Hospitalier Intercommunal de Cré-
teil, France.
The study was funded by the Pediatric Infectious Diseases Group of the French
Pediatrics Society, Association Clinique et Thérapeutique Infantile du Val
de Marne and Pfizer. The National Reference Center for Pneumococci was
partially funded by the French National Health Agency.
R.C., C.L. and E.V. received grants and personal fees from Pfizer. A.M. has had
appointments for consultancy/advice (GSK vaccines, Pfizer) and invitations
to European Society for Paediatric Infectious Disease meetings (GSK vac-
cines, Pfizer); F.D. received fees from Biocodex for 2 lectures.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of
this article on the journal’s website (www.pidj.com).
Address for correspondence: François Dubos, MD, PhD, Pediatric Emergency
Unit & Infectious Diseases, CHU Lille, 2 av. Oscar Lambret, F-59000, Lille,
France. E-mail: francois.dubos@chru-lille.fr.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0891-3668/19/3809-0881
DOI: 10.1097/INF.0000000000002358
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P neumococcal meningitis (PM) is a major cause of morbidity and
mortality in infants and children.1–3 PM in infants and children
results in sequelae in 30%–50% of cases and death in 10.4%–11.4%,
with no improvement in prognosis despite the introduction of pneu-
mococcal conjugate vaccines (PCVs).1,4,5 In rare occasions, some
children may have multiple episodes of PM. PM is recurrent when it
occurs in the same individual more than 1 month after the first episode.
It is distinguished from relapse, which represents early recurrence (<1
month after the first episode) due to inappropriate treatment, duration
of treatment or failure to treat the source of the infection.
The prevalence of recurrent invasive pneumococcal diseases
(IPDs) is estimated at 1.7%–10%.6–12 Of these, 11%–65% are recur-
rent PM (RPM).6–8,12 The recurrence of IPDs in general should raise
suspicions of circumstances contributing to reinfection, found in
50%–93% of cases.7–9,12 In children, the recurrence of IPD is linked
to immune deficiency (ID),7,12 anatomic defects such as cerebrospinal
fluid (CSF) leakage7,12 or cochlear implants.13,14 Knowledge of child-
hood risk factors for recurrent IPD is becoming increasingly clear, but
few studies have specifically addressed RPM. CSF leakage is thought
to be a predisposing factor for PM in 12%–22% of single PM (SPM)
cases5,15,16 and 30% of recurrent meningitis cases in children.17
The main purpose of this study was to estimate the frequency
of RPM in children by using the national Association Clinique et
Thérapeutique Infantile du Val de Marne (ACTIV)/Group of Pedi-
atric Infectious Diseases (GPIP) database. Secondary objectives
were to assess risk factors for RPM and to describe the outcome for
children with RPM.
MATERIALS AND METHODS
Study Design and Inclusion Criteria
A multicenter case–control study was conducted by using
the prospective national database of bacterial meningitis in chil-
dren. Since 2001, the National Observatory of Bacterial Meningitis
in children created by and ACTIV/GPIP has collected data on bac-
terial meningitis cases from 222 pediatric units and 168 microbiol-
ogy laboratories throughout France. Participating units report all
cases of bacterial meningitis. The data are representative of more
than 60% of all bacterial meningitis cases.5,18 This study used data
collected from January 2001 to September 2015. The data collec-
tion was approved by the Commission Nationale Informatique et
Libertés (CNIL, no. 913006). Patients and parental consent were
not required for this observational and retrospective study, approved
by the Créteil Ethics Committee. Inclusion criteria were 18 years
of age or younger and a diagnosis of PM declared to the national
network during the study period. The primary endpoint was the fre-
quency of RPM. Secondary endpoints were to assess risk factors
for RPM and describe the outcome for children with RPM.
Definitions
PM was defined by the presence of clinical and CSF signs
of meningitis and culture of Streptococcus pneumoniae in CSF
or blood and/or positive pneumococcal antigens or polymerase
Darmaun et al The Pediatric Infectious Disease Journal  •  Volume 38, Number 9, September 2019
FIGURE 1.  Details of the selection of cases (RPM) and
controls (SPM) from the ACTIV national pediatric meningitis
database.
chain reaction results in CSF.4,5 Cases were all children 18 years
of age or younger, with RPM defined as the presence of at least
2 episodes of PM with an interval between episodes of at least
28 days identified in the national database during the study
period. Each case was matched to 2 randomized controls identi-
fied in the national database (Fig. 1) who had SPM in the year
of the first PM episode in the case and were born the same year.
The winter season was defined by the period between Decem-
ber and March. Risk factors for PM identified in the literature
were CSF leakage, presence of a ventricular shunt, congenital
or acquired ID, any type of asplenia and presence of a cochlear
implant.4,15 Risk factors for CSF leakage were trauma (surgical
or not), inflammation, congenital factors and neoplasm.19 For
patient outcomes, deaths were those resulting from the men-
ingitis episode; deafness was defined by a significant hearing
loss and needing regular follow-up with an ear, nose and throat
(ENT) specialist and hearing aids. Neurologic sequelae included
epilepsy, sensory-motor deficiency and mental deficiency, all
requiring follow-up in a neuropediatric unit.
Process of Data Collection
Cases and controls were identified in the ACTIV/GPIP
national database. For each PM episode, we collected data on
anamnestic (sex, age and season at admission, presence of siblings,
risk factors for IPD), vaccinal (PCV7, PCV13 data), clinical (ENT
infection, seizure, coma, septic shock, purpura, assisted mechani-
cal ventilation), biologic (blood cell count, C-reactive protein
and procalcitonin levels, CSF data, search for ID), microbiologic
(method of pneumococcal identification, serotype if available and
antimicrobial susceptibility) and therapeutic (antimicrobial and
steroid treatment) features. Additional data on the outcome (com-
plications, search for and treatment of CSF leakage, intensive care
unit admission, sequelae and death) were retrospectively collected
from the pediatric units.
Microbiology
S. pneumoniae was identified by standard methods in the
microbiology laboratory of each hospital. Isolates were serotyped
at the National Reference Center for pneumococci by latex agglu-
tination with antisera provided by the Statens Serum Institute
(Copenhagen, Denmark). Antimicrobial susceptibility testing for
penicillin and ceftriaxone or cefotaxime was performed at National
Reference Center for pneumococci as previously described.1
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Statistical Analyses
The frequency of RPM cases in the national database was
first calculated. Then, characteristics of children were compared
between the first PM episode in cases and the PM episode in con-
trols. The distribution of cases and controls over the study period
was described. All PM episodes in cases were compared with the
PM episode in controls. Cases and controls were compared for
patient outcomes and risk factors for PM. Quantitative data were
analyzed by Student t test or nonparametric Mann-Whitney U test
as applicable. Categorical data were analyzed by χ2 or Fisher exact
test. The analysis was performed with the software Epi-Info 6.04fr
(US Centers for Disease Control and Prevention, Atlanta, GA) and
Stata SE 13.1 (Stata Corp, College Station, TX). P <0.05 was con-
sidered statistically significant.
RESULTS
From 2001 to September 2015, we collected data on 1634
cases of PM in 1596 children (median age: 1.0 years [interquar-
tile range: 0.5–4.2]; male/female ratio: 1.39). In total, 24 (1.5%)
patients presented RPM, with 2 or more PM episodes. The median
time between the first and the second episode was 21 months (inter-
quartile range: 6–37). The distribution of first PM episodes in cases
(and controls) was homogeneous over the study period, with a peak
in 2007–2008 (see appendix, Supplemental Digital Content 1;
http://links.lww.com/INF/D477). These 24 patients were matched
to 48 controls with an SPM. Thus, we included 72 children (median
age: 3.9 years [2.5–7.5]; male/female ratio: 1.25) with a total of 110
episodes of PM (Fig. 1).
The comparison of the first PM episode in cases with the
PM episode in controls and all PM episodes between cases and
controls is presented in Table 1. The frequency of ENT infections
was higher in controls than cases. RPM cases were less frequent
than SPM cases during the winter season (27% vs. 48%, P = 0.03).
Cases and controls did not differ in the proportion of identified
PCV serotypes (15/47 [32%] vs. 18/34 [53%], P = 0.06). In these
patients, PCV serotypes were no longer identified after 2010. Sero-
type 24F was the most common non-PCV serotype identified (see
appendix, Supplemental Digital Content 2; http://links.lww.com/
INF/D478). Cases and controls did not differ in penicillin suscepti-
bility (69% vs. 81%, P = 0.11). Seizures overall were less frequent
in cases than controls (11% vs. 29%, P = 0.02). The only difference
in blood tests was for blood cultures, less often positive in first PM
episodes for cases than controls (50% vs. 76%, P=0.05). Among
38 RPM cases, 8 (21%) occurred in 6 children with antimicrobial
prophylaxis (penicillin V).
The rate of abnormal psychomotor development before the
first episode of PM was more frequent in cases than controls when
considering all episodes (47% vs. 22%, P=0.01) (Table 1). Other
short-term outcome and sequelae did not differ between cases and
controls (Table 2).
At the first PM episode, cases and controls did not differ in
identified predisposing factors for PM (Table 3). ID was searched
in 48% of all PM episodes and was more frequent in cases than
controls (58% vs. 29%, P = 0.01). Only 1 additional ID was
detected, in controls. At the end of all episodes, ID was searched
in 88% of cases (see table, Supplemental Digital Content 3; http://
links.lww.com/INF/D479). The IDs were congenital (n = 4; 1 Down
syndrome and 3 functional asplenia) and acquired (n = 3; 1 HIV
infection, 1 myelodysplastic disease and 1 chemotherapy for brain
tumor). Brain imaging was performed in 86% of all PM episodes,
with no differences between cases and controls. After the first epi-
sode, brain imaging was considered normal in 32/59 PM episodes
(54%), with no differences between cases and controls (55% vs.
54%, P = 0.93).
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The Pediatric Infectious Disease Journal  •  Volume 38, Number 9, September 2019 Recurrent Pneumococcal Meningitis

TABLE 1.  Description of the Population With RPM (Cases) Compared With 48 Children With
SPM Episodes (Controls)

Cases (RPM) Controls (SPM) P* P†

First Episode All Episodes

Variables (n = 24) (n = 62) (n = 48)

Male/female ratio 1.40 — 1.86 0.74 —

Premature birth, n/N (%) 6/21 (29) — 3/32 (9) 0.13 —
Median age, years (IQR) 3.8 (2.6 to 7.2) 6.1 (3.0 to 10) 4.0 (2.5 to 8.0) 0.82 0.08
Median weight, SD (IQR) −0.25 (−1.0 to 1.0) 0.5 (−1.0 to 1.0) 0.0 (−1.0 to 1.0) 0.34 0.70
Pre-PM abnormal psychomotor 8/21 (38) 27/57 (47) 8/37 (22) 0.18 0.01
development, n/N(%)
Community childcare, n/N (%) 19/23 (83) 54/60 (90) 31/39 (79) 1.00 0.14
≥1 Sibling, n/N (%) 9/20 (45) 25/54 (47) 15/28 (54) 0.56 0.53
PCV status‡§
 No PCV, n (%) 11 (46) 24 (39) 24 (50) 0.70 0.20
 PCV 7, n (%) 9 (37) 25 (40) 17 (35) 0.90 0.60
 PCV 13, n (%) 4 (17) 13 (21) 7 (15) 1.00 0.54
Wintertime, n‡ (%) 6 (25) 17 (27) 23 (48) 0.06 0.03
Clinical presentation
 Associated ENT infection, n/N (%) 7/23 (30) 16/58 (28) 27/48 (56) 0.04 <0.01
  Acute otitis media, n/N (%) 6/23 (26) 10/58 (17) 15/48 (31) 0.66 0.09
  Other ENT infection, n/N (%) 3/24 (13) 9/61 (15) 16/47 (34) 0.05 0.02
 Seizures¶, n/N (%) 3/24 (13) 7/61 (11) 14/48 (29) 0.12 0.02
 Shock, n/N (%) 7/24 (29) 12/61 (20) 12/48 (25) 0.71 0.50
 Purpura, n/N (%) 3/21 (14) 6/56 (11) 6/41 (15) 0.64 0.56
 Purpura fulminans, n/N (%) 0/23 (0) 2/60 (3) 1/48 (2) 0.68 1.00
 Assisted ventilation, n/N (%) 7/23 (30) 14/61 (23) 19/48 (40) 0.45 0.06
 Coma, n/N (%) 10/23 (44) 21/61 (34) 21/48 (44) 0.99 0.32
IQR indicates interquartile range.
*First cases vs. controls.
†All cases vs. controls.
‡No missing data.
§Twenty-three percent of cases before 2006: none had received PCV; 48% of cases between 2006 and 2010: 58% received the PCV; 29% of cases
after 2011: 97% received the PCV.
¶Seizures before or during antimicrobial treatment.

TABLE 2.  Number of PM-Related Deaths and Short and Long-Term

Outcome of Patients Alive After a Single and Multiple Episodes of PM

Cases (n=24) Controls (n = 48)

After First PM After Last PM

Outcome n/N (%) n/N (%) n/N (%) P* P†

Death — 4/24 (17) 7/48 (15) — 1.00

Deafness 7/20 (35) 5/20‡ (25) 10/31 (32) 0.84 0.58
Neurologic sequelae 10/23 (44) 11/20 (55) 12/36 (33) 0.43 0.11
 Epilepsia 2/23 (9) 4/20 (20) 3/36 (8) 1.00 0.67
 SM deficiency 6/23 (26) 5/20 (25) 11/36 (31) 0.71 0.12
 Mental deficiency 6/23 (26) 5/20 (25) 2/36 (6) 0.05 0.17
*First cases vs. controls.
†Last cases vs. controls.
‡Two patients with deafness after the first PM died.
SM indicates sensory-motor

At the first PM episode, CSF leakage was identified as a
predisposing factor in 25% of cases and 11% of controls (P=0.12)
(Table 3). At the end of all episodes, CSF leakage was identified
in 20 cases and 5 controls (83% vs. 10%, P<0.01). Nine (64%)
cases of congenital CSF leakage were located in the anterior cra-
nial fossa. The predisposing factor was still unclear in 4 cases, 3 of
whom died of the PM.
DISCUSSION
The rate of RPM in children was 1.5%, representing 3.8% of
1634 PM cases over a 15-year period. RPM cases were significantly
less frequent than SPM cases in winter, with fewer concomitant
ENT infections. CSF leakage was highly frequent in RPM cases
when compared with SPM cases (83% vs. 10%, P < 10−7). No ID
was found in RPM cases, but 15% of controls had an ID previously
known or discovered after the PM episode (P = 0.09).
The rate of RPM in our study is close to data previously
reported. In 1999, Drummond et al17 reported a 1.3% prevalence
of recurrent bacterial meningitis in children. A multicenter study
in Denmark performed between 1980 and 2013 found 59/2418
(2.4%) children with recurrent IPDs, 24 of whom experienced 1 or
more PM episodes.12 We show that RPM cases were less predomi-
nant in winter when compared with SPM cases. The predominant

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Darmaun et al The Pediatric Infectious Disease Journal  •  Volume 38, Number 9, September 2019

TABLE 3.  PM Predisposing Factors at the Last PM Episode in Children With

RPM (Cases) and SPM (Controls)

Cases Controls
Variables (n = 24) (n = 48) P

CSF leakage, n (%) 20 (83) 5 (10) <0.01

 Congenital 12 2 0.62
  Previously known 1 1 —
  Discovered after the 1st PM episode 2 1 —
  Discovered after the 2nd PM episode 7 — —
  Discovered after the 3rd PM episode 2 — —
Traumatic 8 3 0.62
  Previously known 2 3 —
  Discovered after the 1st PM episode 2 0 —
  Discovered after the 2nd PM episode 1 — —
  Discovered after the 3rd PM episode 2* — —
  Discovered after the 4th PM episode 0 — —
  Discovered after the 5th PM episode 1* — —
Search for immune deficiency after the 1st PM episode, n (%) 14 (58) 14 (29) 0.01
Immune deficiency identified, n (%) 0 (0) 7 (15) 0.09
 Congenital 0 4 —
  Previously known 0 3 —
  Discovered after the PM episode 0 1 —
 Acquired 0 3 —
  Previously known 0 3 —
  Discovered after the PM episode 0 0 —
Others†, n (%) 3 (13) 1 (2) 0.10
CSF leakage predisposing factors‡, n/N (%) 8/24 (33) 8/41 (20) 0.21
In cases, brain imaging was performed in 19/24 cases after the 1st PM episode, 22/24 after the 2nd PM episode, 8/9
after the 3rd PM episode, 3/3 after the 4th PM episode, and 2/2 after the 5th PM episode.
*In patients with known congenital CSF leakage with surgery.
†Among other predisposing PM risk factors, 1 case and 1 control had a ventriculoperitoneal shunt catheter, and 2
cases had a cochlear implant.
‡Risk factors for CSF leakage were trauma (surgical or not), inflammatory, congenital and neoplasm.

occurrence in winter of IPDs is reported in the literature, with a
peak in February in the northern hemisphere.6,20,21 Several studies
have shown a link between seasonal viral infections (influenza, res-
piratory syncytial virus) and the occurrence of PM21 and IPD.20,22–24
Because RPM was linked to the presence of CSF leakage, a winter-
promoting factor was probably not necessary.
Many clinical cases have been published on the association
between CSF leakage and RPM25–28 but not as systematically as
our series. In the recurrent IPD cases in the study by Ingels et al,12
only 4/24 patients (17%) with 1 or more PM episodes showed
CSF leakage. Alsina et al7 described 3 RPM cases in their recur-
rent IPD cohort: all had CSF leakage. More generally for recur-
rent IPDs, CSF leakage was identified in 7%–75% of patients7,8,12
but sometimes never.9 The original feature of our study is that
CSF leakage was the only source of infection found when the IPD
was an RPM.
In our population, most congenital CSF leakage cases
(58%) were diagnosed after the second PM episode. Therefore,
for the others, there was a real delay in the initial diagnosis of
CSF leakage. However, 33% of cases had a predisposing history of
CSF leakage at the first episode (previous neurosurgery or inner-
ear surgery). The risk of CSF leakage is estimated at 6.3% after
craniotomy in children29 and from 0.9% to 8.5% after transsphe-
noidal endoscopic surgery.30,31 In our study, after the first PM epi-
sode, the source of infection remained unknown in 63% of cases
and 75% of controls (P = 0.3). After all episodes, no source was
found for 4 of the 24 RPM cases (17%), including 3 who died of
the PM and for whom investigations were not possible. The last
patient had a full search for ID and underwent magnetic resonance
imaging twice, with images examined at least twice to search for
CSF leakage, which was not identified. No ID was found in cases,
whereas 13% of controls had ID known before their PM. In the
study by Gaschignard et al,6 ID was found in 26/163 patients with
IPD (16%; 95% CI, 11–22) but in none of the 11 with RPM. In the
study by Mason et al,8 10/108 recurrent IPD cases were RPM; of
these 108 cases, 15 experienced more than 2 IPDs, and of these 15,
only 1 had RPM, with Mondini deformity. In the study by Ingels et
al,12 among the 10 patients with at least 3 IPD episodes, only one
had RPM that was related to CSF leakage. Seven of the remaining
9 cases of recurrent pneumococcal bacteremia had an identified
ID.12 In another Spanish study of 23 recurrent IPD cases in 10
patients, 2 cases exhibited ID.7
The short-term evolution of RPM was comparable to that
of SPM. From the first recurrence, the PM was even less clinically
severe in cases than controls (fewer seizures, less ventilatory assis-
tance), which could be explained by earlier in-hospital medical
advice by parents who recognized the first meningitis symptoms
early. The absence of differences in neurologic outcome and death
between cases and controls may also be related to this early medical
alertness by parents of children with RPM. However, it may also
be due to the exclusion of patients who died or to a lack of power
because of the small number of patients.
Although recruitment was multicenter for almost 15 years,
RPM remained a rare event, with a small study sample (n = 24).
The number (but not the rate) may be underestimated, because
the completeness of the ACTIV database is estimated at 61%.18 In
addition, for children whose first episode occurred at the end of
the study period, recurrence could not be reported. To the best of
our knowledge, this is the only study that exclusively addressed
RPM. Because of the study design and age matching, we could
not compare the occurrence of PM at different ages between the 2
groups. However, the median age of patients with SPM in the whole
ACTIV register was much lower than that of patients with RPM (1
vs. 3.9 years).1 The PCV coverage rate may appear low; however,

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The Pediatric Infectious Disease Journal  •  Volume 38, Number 9, September 2019 Recurrent Pneumococcal Meningitis
children were included from 2001 to 2015, and PCV vaccination
was introduced in 2006, with progressively increasing vaccination
coverage. In total, 25 PM episodes (23%) occurred before 2006.
Among children with PM occurring after 2006, 77% were vacci-
nated; 97% after 2011. Although the ACTIV data collection was
prospective, some additional data were retrospectively collected,
which may have led to information bias in some files. However, the
Observatory’s questionnaires were completed when the PM episode
occurred, which limited information bias. Data for clinical obser-
vations and pre- or post-PM blood tests were not always complete.
Regardless, we returned to the source records for all patients to
obtain the greatest accuracy of the data collected. Only 39% of all
patients and 58% of those with RPM were screened for ID. This
low rate may be explained by the lack of ID searches in the early
years of the study, because the relation between IPDs and ID was
not well established at that time. The case–control design of the
study was chosen to limit bias and was the most appropriate for
such rare events.
In France, the implementation of PCV7 then PCV13 with
high vaccination coverage (>91% in 2011, http://invs.santepub-
liquefrance.fr/) led to a 38% decrease in PM incidence (95% CI,
−56.1 to −20.4) in children <15 years of age.32 After this period,
the PM incidence increased and was linked to a serotype replace-
ment by nonvaccine serotypes, especially the emerging serotype
24F, which started in 2015.32 In our study, among all 110 episodes
of PM, 33 (30%) cases were due to PCV serotypes, with no differ-
ences between cases and controls. After 2010, no PCV serotype
was found in patients receiving PCV13. During this period, PM
episodes were mostly due to serotype 24F in controls and serotypes
15A and 15C in cases. Patients with underlying conditions, includ-
ing CSF leakage, tend to be infected by non-PCV serotypes.33
With the data we present, it seems possible to propose a
hypothesis of a pathophysiologic mechanism of these RPM cases,
different from SPM. An anatomic abnormality (CSF leakage) may
be the main factor in the development of RPM. Thus, an ENT ori-
gin (otitis or other local infection) or the occurrence of a predispos-
ing winter viral infection may not be entirely necessary. The lower
level of positive blood cultures in RPM than SPM cases could mean
that the CSF leakage would be sufficient to promote PM by loco-
regional diffusion with less bacteremia.
We emphasize the importance of searching for a predis-
posing factor (ie, ID or CSF leakage) in any episode of PM. CSF
leakage should be searched for especially when the PM occurs
outside the winter period and/or without any concomitant ENT
infection. Any recurrence of PM should always lead to an active
search for CSF leakage. A literature review proposed the follow-
ing recommendations34: β-transferrin test for clear rhinorrhea;
if positive, cerebral and facial mass computed tomography scan
first and cerebral magnetic resonance imaging with cisternogra-
phy second. Searching for and treating the source of infection is
imperative to limit the risk of neurologic consequences second-
ary to the PM recurrence.
ACKNOWLEDGMENTS
We are grateful to all the pediatricians and microbiologists
who collected the data via the National Observatory of Bacterial
Meningitides, as well as to the employees of Association Clinique
et Thérapeutique Infantile du Val de Marne and the National Refer-
ence Center for pneumococci for their help.
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