The causative organisms of bacterial meningitis in Korean children in 1996-2005.

Abstract

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood, despite the availability of effective vaccines against Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The purpose of this study was to analyze data on bacterial meningitis cases in Korea from 1996 through 2005. The information of all hospitalized bacteria-proven meningitis cases was obtained from 17 university hospitals nationwide. A total of 402 cases were identified. Of these, 125 (29.9%) cases were neonates. Streptococcus agalactiae was the most common bacteria responsible for 99 (24.6%) of all cases regardless of age, followed by S. pneumoniae for 91 (22.6%) and H. influenzae for 67 (16.7%) patients. The common etiology beyond the neonatal period was S. pneumoniae for 91 (33.0%) followed by H. influenzae for 63 (22.8%) patients. The overall case fatality rate was 9.4%, which was similar with that in 1986-1995. In conclusion, S. agalactiae, S. pneumoniae and H. influenzae were important etiologic agents of bacterial meningitis in children in the last 10 yrs. It is required to establish the preventive strategy of the three bacteria. The nationwide epidemiologic study should be continued to evaluate immunization strategy and efficacy.

Full text

Page 1

INTRODUCTION
Despite increased availability of potent antimicrobials and
effective vaccines, bacterial meningitis continues to be a sig-
nificant cause of childhood morbidity and mortality. Many
clinical and etiologic studies performed over the past decades
have demonstrated that different species of bacteria cause puru-
lent meningitis. In neonatal period, Streptococcus agalactiae
and Gram-negative bacilli cause most bacterial meningitis
(1, 2). Haemophilus influenzae, Neisseria meningitidis and Strep-
tococcus pneumoniae were the most common causative organ-
isms of bacterial meningitis worldwide in childhood (3, 4).
In Korea, there was a report representing the basic epidemi-
ologic data of bacterial meningitis in children during the pre-
vious ten years (1986-1995) (5). Thereafter, new vaccines
such as Haemophilus influenza type b (Hib) conjugate vaccine
and heptavalent pneumococcal conjugate vaccine have been
introduced and many changes of the epidemiologic profile
are expected in Korea. Particularly, Hib vaccine was proved
to have good immunogenicity in Korean infants (6). Although
decline of invasive Hib diseases including meningitis has been
reported in many countries after the routine immunization
of Hib vaccine (7, 8), there is little investigation about child-
hood bacterial meningitis in Korea. Some studies demon-
strated that the incidence of Hib meningitis had decreased
after the introduction of Hib vaccine (9, 10). However, as
895
Hye Kyung Cho
Jin Han Kang
Dong Soo Kim
Jung Soo Kim
Chang Hwi Kim
Su-Eun Park
Eun Hee Chung
Young Youn Choi
Young Jin Hong
and Kyung-Hyo Kim
1, Hyunju Lee
2, Kwang Nam Kim
4, Yun Kyung Kim
6, Jong-Hyun Kim
7, Hwang Min Kim
9, Sung Hee Oh
11, Sung Ho Cha
13, Jae Kyun Hur
14, Hoan Jong Lee
1
1,
3,
5,
2,
8,
10,
12,
2,
15,
Department of Pediatrics, School of Medicine, Ewha
Womans University1, Seoul; College of Medicine, The
Catholic University of Korea2, Seoul; College of
Medicine, Hallym University3, Seoul; Yonsei University
College of Medicine4, Seoul; College of Medicine,
Korea University5, Ansan; Chonbuk National
University, College of Medicine6, Jeonju; College of
Medicine, Soonchunhyang University7, Bucheon;
Yonsei University Wonju College of Medicine8, Wonju;
School of Medicine, Busan National University9, Busan;
Hanyang University College of Medicine10, Seoul;
Dankook University College of Medicine11, Cheonan;
Kyunghee University School of Medicine12, Seoul;
Chonnam National University Medical School13, Gwangju;
Inha University College of Medicine14, Incheon; Seoul
National University College of Medicine15, Seoul, Korea
Address for Correspondence
Kyung-Hyo Kim, M.D.
Department of Pediatrics, School of Medicine, Ewha
Womans University, 204 Anyangcheon-gil,
Yangcheon-gu, Seoul 158-710, Korea
Tel : +82.2-2650-2857, Fax : +82.2-2650-2561
E-mail : kaykim@ewha.ac.kr
J Korean Med Sci 2010; 25: 895-9ISSN 1011-8934
DOI: 10.3346/jkms.2010.25.6.895
The Causative Organisms of Bacterial Meningitis in Korean Children
in 1996-2005
Bacterial meningitis remains a serious cause of morbidity and mortality in childhood,
despite the availability of effective vaccines against Haemophilus influenzae type b
(Hib) or Streptococcus pneumoniae. The purpose of this study was to analyze data
on bacterial meningitis cases in Korea from 1996 through 2005. The information of
all hospitalized bacteria-proven meningitis cases was obtained from 17 university
hospitals nationwide. A total of 402 cases were identified. Of these, 125 (29.9%)
cases were neonates. Streptococcus agalactiae was the most common bacteria
responsible for 99 (24.6%) of all cases regardless of age, followed by S. pneumo-
niae for 91 (22.6%) and H. influenzae for 67 (16.7%) patients. The common etiolo-
gy beyond the neonatal period was S. pneumoniae for 91 (33.0%) followed by H.
influenzae for 63 (22.8%) patients. The overall case fatality rate was 9.4%, which
was similar with that in 1986-1995. In conclusion, S. agalactiae, S. pneumoniae
and H. influenzae were important etiologic agents of bacterial meningitis in children
in the last 10 yrs. It is required to establish the preventive strategy of the three bac-
teria. The nationwide epidemiologic study should be continued to evaluate immu-
nization strategy and efficacy.
Key Words : Meningitis, Bacterial; Etiology; Epidemiology; Streptococcus pneumoniae; Haemophilus influen-
zae; Streptococcus agalactiae; Neisseria meningitidis
Received : 23 September 2009
Accepted : 7 December 2009
ⓒ2010 The Korean Academy of Medical Sciences.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial
License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use,
distribution, and reproduction in any medium, provided the original work is properly cited.

Page 2

these studies were carried out in only one hospital or several
hospitals in a specific region, they might be insufficient to
reflect the general pediatric population in Korea.
This study provides the comprehensive data of bacterial
meningitis in Korean children through a multicenter retro-
spective study for the past decade. Also, it will provide invalu-
able data for comparison of clinical features of the disease in
1986-1995 with those in 1996-2005.
MATERIALS AND METHODS
Data on the medical records of bacterial meningitis patients
aged ≤18 yr admitted to 17 university hospitals through-
out Korea from January 1996 through December 2005, were
reviewed retrospectively. Among the hospitals participated
in this study, six were located in Seoul, another six in cities
nearby Seoul, and each of five hospitals was located in Gang-
won-do (Wonju), Chungcheongnam-do (Cheonan), Jeollabuk-
do (Jeonju), Gwangju, and Busan, respective. All bacteria
isolated in the patients with meningitis were included. Staphy-
lococcusepidermidiscultured in patients with cerebrospinal shunts
were excluded from the analysis. In this study, the criteria for
a definite diagnosis of bacterial meningitis were as following:
1) positive cerebrospinal fluid (CSF) culture of bacterial patho-
gen; 2) positive blood culture of bacteria with clinical features
and CSF findings concordant with bacterial meningitis; and
3) CSF positive for organisms causing bacterial meningitis
by latex agglutinin test and with pleocytosis (≥10 cells/mL)
in patients with meningeal irritative signs. Medical records
were examined for the followings: age, gender, bacterial eti-
ology of meningitis, fatality and complications. Organisms
were identified according to standard procedures in each hos-
pital,but bacterial isolates were not subcultured or serotyped.
RESULTS
During the ten years, 402 patients were hospitalized with
bacterial meningitis in 17 hospitals. Of these, 231 patients
(57.5%) were male, and 169 patients (42.0%) were female
with a male to female ratio of 1.37:1. The ages of infected
children ranged from 0 day to 18 yr with a mean and median
age of 25 months and 3 months, respectively. Most patients
(330 cases, 82.1%) were ≤2 yr of age and 125 (31.2%) cases
were neonates.
S. agalactiae(99 cases, 24.6%) was the most frequent etiolog-
icagent in Korea, followed by S. pneumoniae(91 cases, 22.6%)
and H. influenzae (67 cases, 16.7%). And Escherichia coli (21
cases, 5.2%) and N. meningitidis (18 cases, 4.5%) were impor-
tant pathogens of bacterial meningitis in Korean children.
The category ‘‘others’’ included coagulase negative Staphylo-
coccus (26 cases, 6.5%), Streptococcus (other than S. agalactiae)
(15 cases, 3.7%), Staphylococcus aureus (15 cases, 3.7%), Kleb-
siella pneumoniae (11 cases, 2.7%), Enterococcus sp. (10 cases,
2.5%), Enterobacter cloacae (5 cases, 1.2%), Salmonella sp. (4
cases, 1.0%), Acinetobacter sp. (4 cases, 1.0%), Listeria sp. (3
cases, 0.7%), Pseudomonas aeruginosa (3 cases, 0.7%), Mycobac-
terium tuberculosis, Proteus mirabilis, Flavobacterium indologans
and Gram-negative bacilli (Table 1).
In the first 3 months of life, S. agalactiae (89 of 187, 47.6%)
and E. coli (18 of 187, 9.6%) were common organisms caus-
ingbacterial meningitis. Among S. agalactiae meningitis, only
8 cases presented within 6 days after birth and the remain-
ing cases presented between 7 days and 5 months. The com-
mon etiology beyond the neonatal period and under 5 yr of
age was S. pneumoniae for 32.1% (68 of 212), followed by H.
influenzae for 27.8% (59 of 212). In patients between 5 and
18 yr, S. pneumoniae(23 of 64, 35.9%) and N. meningitidis(15
of 64, 23.4%) were the major etiologic organisms of bacte-
rial meningitis.
Through the ten years, yearly frequency of bacterial menin-
gitis was similar, however the cases of meningitis caused by
H. influenzaehave decreased during the period, especially since
2001 (Fig. 1). Among a total of 67 H. influenzae meningitis
cases, 51 (76.1%) occurred between 1996 and 2000, thus, the
number of cases decreased by a third between 2001 and 2005.
Overall mortality rate was 9.5%. The fatalities as etiolog-
896H.K. Cho, H. Lee, J.H. Kang, et al.
The category ‘‘others’’ included coagulase negative Staphylococcus (26 cases, 6.5%), Streptococcus (other than S. agalactiae) (15 cases, 3.7%),
Staphylococcus aureus (15 cases, 3.7%), Klebsiella pneumoniae (11 cases, 2.7%), Enterococcus species (10 cases, 2.5%), Enterobacter cloacae (5
cases, 1.2%), Salmonella species (4 cases, 1.0%), Acinetobacter species (4 cases, 1.0%), Listeria species (3 cases, 0.7%), Pseudomonas aerugi-
nosa (3 cases, 0.7%), Mycobacterium tuberculosis, Proteus mirabilis, Flavobacterium indologans and gram-negative bacilli.
*Age not determined: 1.
Age of patient Total
No. (%) caused by
S. agalactiaeE. coli H. influenzaeS. pneumoniae N. meningitidis Others
0 month
1-2 month
3-59 month
5-18 yr
Total
59 (47.2)
30 (48.4)
9 (6.0)
00000
98* (24.4)
10 (8.0)
8 (12.9)
3 (2.0)
0000
21 (5.2)
4 (3.2)
7 (11.3)
52 (34.7)
4 (6.3)
67 (16.7)
00000
3 (4.8)
65 (43.3)
23 (35.9)
91 (22.7)
2 (1.6)
0000
1 (0.7)
15 (23.4)
18 (4.5)
50 (40.0)
14 (22.6)
20 (13.3)
22 (34.4)
106 (26.4)
125
62
150
64
401*
Table 1. Age distribution of bacterial meningitis cases according to causative organisms, 1996-2005

Page 3

ic agents were 19.8%, 16.7% and 8.0% for S. pneumoniae, N.
meningitidis and S. agalactiae, respectively (Table 2). There was
no fatal case in meningitis patients caused by H. influenzae.
Various complications were developed in 20.1% of patients;
subdural effusion (7.5%), hydrocephalus (6.2%), hearing
impairment (5.5%), convulsion (3.5%), etc. The incidences
of complications according to etiologic agents were 27.3%,
26.9%, 23.8%, 20.9%, and 5.6% for S. agalactiae,H. influen-
zae,E. coli,S. pneumoniaeand N. meningitidis, respectively.
DISCUSSION
This study provides the epidemiologic data about bacteri-
al meningitis in Korean children during the last decade. We
have shown the basic epidemiologic information of childhood
bacterial meningitis in a previous study. Therefore, these stud-
ies reflect the epidemiologic trend of bacterial meningitis in
Korean children for the last 20 yr. It cannot provide the inci-
dence of bacterial meningitis in the general population of
Korea, but can offer the relative frequency of causative organ-
isms by a multicenter study including hospitals distributed
throughout Korea. This investigation became more repre-
sentative of population characteristics because hospitals locat-
ed in more regions participated in it compared with the pre-
vious study.
From 1996 through 2005, the most common organism
of bacterial meningitis in Korean children was S. agalactiae,
followed by S. pneumoniae and H. influenzae. This result dif-
fers from the previous report that the leading causative organ-
ism of bacterial meningitis was S. pneumoniae (35.0%), fol-
lowed by H. influenzae (34.3%) and N. meningitidis (6.4%)
between 1986 and 1995 (5). However, the main reason of
this difference is due to the fact that the subjects of this study
included neonates. In many developed countries, S. agalacti-
ae caused most bacterial meningitis in the neonatal period
including premature and term babies up to 3 months of life
(11, 12). The incidence of neonatal S. agalactiae infection has
decreased since the implementation of intrapartum chemo-
prophylaxis in the United States and some European coun-
tries (13, 14). In the United States, Center for Disease Con-
trol and Prevention revised national guidelines in 2002, first
issued in 1996, which recommended universal late antenatal
screening of all pregnant women. However, the overall rates
of late-onset disease remained stable in spite of these guide-
lines, that is, it has only influenced the incidence of early-onset
S. agalactiae disease, not that of late-onset disease (1). In this
study 8.1% of S. agalactiae meningitis patients presented
within the first 6 days of life in contrast to the previous report
54.4% and 59.6% in the United States and European coun-
tries, respectively (1, 2). Considering the results of this study,
intrapartum antibiotic prophylaxis might not have a great
The Causative Organisms of Bacterial Meningitis in Korean Children in 1996-2005897
Fig. 1. Yearly distribution of bacterial meningitis according to etiologic agents. The incidence of H. influenzae meningitis has markedly
decreased since 2001.
*The category ‘‘others’’ included coagulase negative Staphylococcus (26 cases, 6.5%), Streptococcus (other than S. agalactiae) (15 cases,
3.7%), Staphylococcus aureus (15 cases, 3.7%), Klebsiella pneumoniae (11 cases, 2.7%), Enterococcus species (10 cases, 2.5%), Enter-
obacter cloacae (5 cases, 1.2%), Salmonella species (4 cases, 1.0%), Acinetobacter species (4 cases, 1.0%), Listeria species (3 cases,
0.7%), Pseudomonas aeruginosa (3 cases, 0.7%), Mycobacterium tuberculosis, Proteus mirabilis, Flavobacterium indologans and Gram-
negative bacilli.
No. of patients
60
50
40
30
20
10
0
’96 ’98 ’98’99 ’00 ’01’02’03’04 ’05
Year
Others*
N. meningitidis
S. pneumoniae
H. influenzae
E. coli
S. agalactiae
Etiology
Case fatality rates
No. of death/No. of patients (%)
Table 2. Case fatality according to causative organisms
S. agalactiae
E. coli
H. influenzae
S. pneumoniae
N. meningitidis
Others
Total
8/99 (8.0)
1/21 (4.8)
0/67 (0.0)
18/91 (19.8)
3/18 (16.7)
8/106 (7.5)
38/402 (9.5)

Page 4

impact in the reduction of S. agalactiaedisease in Korea. Other
preventive strategies of neonatal S. agalactiae infections such
as vaccination against this pathogen might be required.
Beyond the neonatal period, S. pneumoniae and H. influen-
zae were major organisms causing bacterial meningitis dur-
ing the study period. H. influenzae has decreased as a major
pathogen of meningitis during ten years, especially since 2001
after Hib vaccine was introduced in Korea. Hib had been the
highest portion of etiologic agents of childhood bacterial
meningitis when Hib vaccine was not yet introduced (15).
In many countries, after Hib vaccine was introduced in nation-
alimmunization programs invasive infections caused by Hib
reduced by more than 99% (3, 4, 16, 17). Replacement with
other capsular types has not occurred after the introduction
of Hib vaccines (18). In 2006, WHO recommended that Hib
vaccines be included in all routine infant immunization pro-
grams (19). Although H. influenzaeisolates were not routinely
serotyped in this study, the reduced incidence of H. influen-
zae meningitis in Korea can be thought to be contributed
by effectiveness of Hib vaccine because more than 95% of
invasive diseases are caused by type b strain (3). Thus, with
the universal administration of Hib vaccine, further reduc-
tion of the incidence of bacterial meningitis caused by H.
influenzaemay be expected in Korea.
S. pneumoniae is the most common etiology of childhood
bacterial meningitis in the United States and Africa region,
especially where Hib disease has been eliminated by vaccina-
tion (20-22). It is the second most frequently reported cause
of septic meningitis in European and sub-Saharan African
countries following meningococcal cases (23-25). Heptava-
lent pneumococcal conjugate vaccine (PCV7) covers against
seven of the most common and resistant strains (4, 6B, 9V, 14,
18C, 19F, and 23F) of S. pneumoniae. The incidence of pneu-
mococcal meningitis declined by 30.1%, especially nearly
60% in children younger than 5 yr of age after the introduc-
tion of conjugate vaccine against in the United States (26).
However, despite the introduction of PCV7, S. pneumoniae
remains the most common cause of childhood bacterial menin-
gitis in the United States (20). The reason of this has been
attributed to the replacement for pneumococcal meningitis
is observed for non-vaccine serotypes after widespread use of
PCV7, unlike H. influenzae (26). In addition, the circulating
serotypes can vary with geographical areas and relatively high
proportion of serotype 19A has been found among prevalent
serotypes of Korea (27). Thus, 10-valent (including serotype
1, 5 and 7V) and 13-valent vaccine (including serotype 1, 3,
5, 6A, 7F, and 19A) were developed. In this study, S. pneumo-
niae was the most common etiology beyond the neonatal peri-
od and under 5 yr as well as in patients between 5 and 18 yr.
PCV7 was introduced in 2003 in Korea. Because of insuffi-
cient vaccination coverage and slow implementation, decline in
the number of cases of pneumococcal meningitis was not ob-
served in this study. Further studies assessing the incidence of
pneumococcal meningitis in post-vaccination period are needed.
N. meningitidis was the third common agent for last two
decades in Korean children beyond the neonatal period, with
relatively low incidence compared with the United States and
European, African and Middle Eastern Asian countries (4, 12,
23-25, 28). The relative frequency of meningococcal menin-
gitis has increased after the introduction of the Hib vaccine
in the United States (21). Although meningococcus has con-
tributed relatively less to bacterial meningitis in Korean chil-
dren, watching changing incidence is important.
The mortality rate for bacterial meningitis in children re-
ported in various countries ranged from 4% to 10% in more
recent studies (4). Case-fatality rate in this study was great-
estin pneumococcal meningitis similar to that shown in other
studies (4, 21, 29). Death by H. influenzae meningitis was
not found in our data. Reasons for this are that H. influenzae
meningitis can be well recovered when early treatment, includ-
ing the choice of adequate antibiotics, was started. Early use
of dexamethasone can help to decrease inflammation of men-
inges and prevent fatal outcome. Transient and permanent
complications were observed in 20% of patients in this report.
This rate was comparable to other reports where 20-50% of
survivors had serious and permanent sequelae such as epilep-
sy, mental retardation, deafness, learning impairment, sen-
sory-motor deficit and cerebral palsy (29, 30).
Although our study demonstrated the trends and outcomes
of bacterial meningitis in Korean children, some limitations
of the study should be considered. This study included only
the patients who were admitted to university hospitals and
had lumbar punctures. And, antibiotic uses prior to hospital-
izations could make it difficult to detect organisms by culture,
especially before 2000 when antibiotics could be obtained
without a doctor’s prescription in Korea. These might result
in underestimation of the number of bacterial meningitis
cases. Another limitation is that we could not know the long-
term sequelae of the patients because the final outcomes of
the patients were determined at discharge or death.
In conclusion, in the last 10 yrs S. agalactiae andE. coli were
the major etiologic agents of bacterial meningitis in neonates
and infants below 3 months, and S. pneumoniae, H. influenzae
and N. meningitidis in Korean children beyond 3 months.
Establishment of a preventive strategy for S. agalactiaeinfec-
tion in neonates is required. The universal administration of
Hib and pneumococcal conjugate vaccine should be adapt-
ed to the national immunization program. The nationwide
epidemiologic surveillance should be continued to give invalu-
able information which will have a great influence in mak-
ing important decisions on the national vaccination policy
and to evaluate the efficacy of newly adapted vaccines.
REFERENCES
1. Centers for Disease Control and Prevention (CDC). Trends in peri-
natal group B streptococcal disease-United States, 2000-2006.
898H.K. Cho, H. Lee, J.H. Kang, et al.

Page 5

MMWR Morb Mortal Wkly Rep 2009; 58: 109-12.
2. Fluegge K, Siedler A, Heinrich B, Schulte-Moenting J, Moennig MJ,
Bartels DB, Dammann O, von Kries R, Berner R; German Pediatric
Surveillance Unit Study Group. Incidence and clinical presentation
of invasive neonatal group B streptococcal infections in Germany.
Pediatrics 2006; 117: e1139-45.
3. Sáez-Llorens X, McCracken GH Jr. Bacterial meningitis in children.
Lancet 2003; 361: 2139-48.
4. Chávez-Bueno S, McCracken GH Jr. Bacterial meningitis in chil-
dren. Pediatr Clin North Am 2005; 52: 795-810.
5. Kim KH, Sohn YM, Kang JH, Kim KN, Kim DS, Kim JH, Kim CH,
Shin YK, Oh SH, Lee HJ, Cha SH, Hong YJ, Sohn KC. The causative
organisms of bacterial meningitis in Korean children, 1986-1995. J
Korean Med Sci 1998; 13: 60-4.
6. Kim KH, Lee H, Chung EH, Kang JH, Kim JH, Kim JS, Lee HJ,
Oh SH, Park EA, Park SE. Immunogenicity and safety of two differ-
ent Haemophilus influenzae type b conjugate vaccines in Korean
infants. J Korean Med Sci 2008; 23: 929-36.
7. Cowgill KD, Ndiritu M, Nyiro J, Slack MP, Chiphatsi S, Ismail A,
Kamau T, Mwangi I, English M, Newton CR, Feikin DR, Scott JA.
Effectiveness of Haemophilus influenzae type b Conjugate vaccine
introduction into routine childhood immunization in Kenya. JAMA
2006; 296: 671-8.
8. Adegbola RA, Secka O, Lahai G, Lloyd-Evans N, Njie A, Usen S,
Oluwalana C, Obaro S, Weber M, Corrah T, Mulholland K, McAdam
K, Greenwood B, Milligan PJ. Elimination of Haemophilus influen-
zae type b (Hib) disease from The Gambia after the introduction of
routine immunisation with a Hib conjugate vaccine: a prospective
study. Lancet 2005; 366: 144-50.
9. Lee YJ, Lee SJ, Park HJ, Lee YH, Kang SY, Kim YC, Lee IK, Lee
KY, Lee KS, Kim WS. A clinical study of child bacterial meningitis
in Daejeon and Chungcheong area: 2001-2005. Korean J Pediatr
2007; 50: 157-62.
10. Kim HJ, Lee JW, Lee KY, Lee HS, Hong JH, Hahn SH, Whang KT.
Causative organisms in children with bacterial meningitis (1992-
2002). J Korean Pediatr Soc 2003; 46: 1085-8.
11. Sáez-Llorens X, McCracken GH Jr. Antimicrobial and anti-inflam-
matory treatment of bacterial meningitis. Infect Dis Clin North Am
1999; 13: 619-36.
12. Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M, Rein-
gold AL, Lefkowitz L, Perkins BA. Bacterial meningitis in the Unit-
ed States in 1995. Active Surveillance Team. N Engl J Med 1997;
337: 970-6.
13. Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH,
Petit S, Craig AS, Schaffner W, Zansky SM, Gershman K, Stefonek
KR, Albanese BA, Zell ER, Schuchat A, Schrag SJ. Epidemiology
of invasive group B streptococcal disease in the United States, 1999-
2005. JAMA 2008; 299: 2056-65.
14. López Sastre JB, Fernández Colomer B, Coto Cotallo GD, Ramos
Aparicio A; Grupo de Hospitales Castrillo. Trends in the epidemiol-
ogy of neonatal sepsis of vertical transmission in the era of group B
streptococcal prevention. Acta Paediatr 2005; 94: 451-7.
15. Mendsaikhan J, Watt JP, Mansoor O, Suvdmaa N, Edmond K, Litt
DJ, Nymadawa P, Baoping Y, Altantsetseg D, Slack M. Childhood
bacterial meningitis in Ulaanbaatar, Mongolia, 2002-2004. Clin
Infect Dis 2009; 48 Suppl 2: S141-6.
16. Kalies H, Siedler A, Gröndahl B, Grote V, Milde-Busch A, von Kries
R. Invasive Haemophilus influenzae infections in Germany: impact
of non-type b serotypes in the post-vaccine era. BMC Infect Dis 2009;
9: 45.
17. Lewis RF, Kisakye A, Gessner BD, Duku C, Odipio JB, Iriso R,
Nansera D, Braka F, Makumbi I, Kekitiinwa A. Action for child sur-
vival: elimination of Haemophilus influenzae type b meningitis in
Uganda. Bull World Health Organ 2008; 86: 292-301.
18. Kelly DF, Moxon ER, Pollard AJ. Haemophilus influenzae type b
conjugate vaccines. Immunology 2004; 113: 163-74.
19. World Health Organization. WHO position paper on Haemophilus
influenzae type b conjugate vaccines. Wkly Epidemiol Rec 2006; 81:
445-52.
20. Nigrovic LE, Kuppermann N, Malley R; Bacterial Meningitis Study
Group of the Pediatric Emergency Medicine Collaborative Research
Committee of the American Academy of Pediatrics. Children with
bacterial meningitis presenting to the emergency department during
the pneumococcal conjugate vaccine era. Acad Emerg Med 2008;
15: 522-8.
21. Neuman HB, Wald ER. Bacterial meningitis in childhood at the Chil-
dren’s Hospital of Pittsburgh: 1988-1998. Clin Pediatr (Phila) 2001;
40: 595-600.
22. Centers for Disease Control and Prevention (CDC). Pediatric bac-
terial meningitis surveillance- African region, 2002-2008. MMWR
Morb Mortal Wkly Rep 2009; 58: 493-7.
23. Giorgi Rossi P, Mantovani J, Ferroni E, Forcina A, Stanghellini E,
Curtale F, Borgia P. Incidence of bacterial meningitis (2001-2005)
in Lazio, Italy: the results of a integrated surveillance system. BMC
Infect Dis 2009; 9: 13.
24. Theodoridou MN, Vasilopoulou VA, Atsali EE, Pangalis AM, Mos-
trou GJ, Syriopoulou VP, Hadjichristodoulou CS. Meningitis reg-
istry of hospitalized cases in children: epidemiological patterns of
acute bacterial meningitis throughout a 32-year period. BMC Infect
Dis 2007; 7: 101.
25. Campagne G, Schuchat A, Djibo S, Ousséini A, Cissé L, Chippaux
JP. Epidemiology of bacterial meningitis in Niamey, Niger, 1981-96.
Bull World Health Org 1999; 77: 499-508.
26. Hsu HE, Shutt KA, Moore MR, Beall BW, Bennett NM, Craig AS,
Farley MM, Jorgensen JH, Lexau CA, Petit S, Reingold A, Schaffn-
er W, Thomas A, Whitney CG, Harrison LH. Effect of pneumococ-
cal conjugate vaccine on pneumococcal meningitis. N Engl J Med
2009; 360: 244-56.
27. Choi EH, Kim SH, Eun BW, Kim SJ, Kim NH, Lee J, Lee HJ. Strep-
tococcus pneumoniae serotype 19A in children, South Korea. Emerg
Infect Dis 2008; 14: 275-81.
28. Husain EH, Al-Shawaf F, Bahbahani E, El-Nabi MH, Al-Fotooh KA,
Shafiq MH, Al-Ateeqi N, Abo Talib MA. Epidemiology of child-
hood meningitis in Kuwait. Med Sci Monit 2007; 13: CR220-3.
29. Baraff LJ, Lee SI, Schriger DL. Outcomes of bacterial meningitis in
children: a meta-analysis. Pediatr Infect Dis J 1993; 12: 389-94.
30. Grandgirard D, Leib SL. Strategies to prevent neuronal damage in
paediatric bacterial meningitis. Curr Opin Pediatr 2006; 18: 112-8.
The Causative Organisms of Bacterial Meningitis in Korean Children in 1996-2005 899