European Journal of Clinical Microbiology & Infectious Diseases (2018) 37:723–728

https://doi.org/10.1007/s10096-017-3165-7

Capsular genotype and lipooligosaccharide locus class

distribution in Campylobacter jejuni from young children with
diarrhea and asymptomatic carriers in Bangladesh
Z. Islam1 & S. K. Sarker1 & I. Jahan1 & K. S. Farzana1 & D. Ahmed1 & A. S. G. Faruque2 & P. Guerry3 & F. Poly3 &
A. P. Heikema4 & H. P. Endtz1,4,5

Received: 21 October 2017 /Accepted: 27 November 2017 /Published online: 21 December 2017
# Springer-Verlag GmbH Germany, part of Springer Nature 2017

Abstract
Campylobacter jejuni-related diarrheal diseases is one of the major health issues among young children (0–59 months old)
in lowincome countries. Monitoring of the capsular (capsule polysaccharide, CPS) types of virulent C. jejuni strains in
regions where the disease is endemic is of great importance for the development of a customized capsule-based
multivalent vaccine. Therefore, we aimed to determine the prevalence of CPS genotypes among C. jejuni strains isolated
from young children with enteritis (n = 152) and asymptomaticcarriers matchedbyage,sex, andresidence
definedasthecontrolgroup (n = 215) in Bangladesh. CPSgenotyping was performed using a newly established multiplex
polymerase chain reaction (PCR) method and lipooligosaccharide (LOS) locus classes (A–E) were characterized using
PCR as well. We identified 24 different CPS genotypes among the 367 isolates. Four prevalent capsular types, HS5/31
complex (n = 27, 18%), HS3 (n = 26, 17%), HS4A (n = 10, 7%), and HS8/17 (n = 10, 7%) covered almost 50% of the
strains from enteritis patients and 43% of the isolates from controls. In combination, the CPS genotype and LOS class was
not discriminative between cases and controls. Dominant capsular types previously identified in C. jejuni strains isolated
frompatientswithGuillain–BarrésyndromeinBangladeshwererarelydetectedinstrainsisolatedfromtheyoungchildren.Asimilar
distribution was evident among enteritis- and control-related strains when comparison was done between CPS types and
LOS classes. This is the first systematic study presenting the distribution of CPS genotypes of C. jejuni strains isolated in
Bangladesh from children with diarrhea and controls, with capsular genotypes HS5/31 complex, HS3, HS4A, and HS8/17
being prevalent in both. In conclusion, systematic studies are required to develop a multivalent capsule-based vaccine for
children in low-income countries.
Introduction Diarrhoeal Disease Research, (icddr,b), Dhaka, Bangladesh
3
Naval Medical Research Center, Silver Spring, MD, USA
Campylobacter jejuni is one of the most frequent 4
Department of Medical Microbiology and Infectious Diseases,
pathogens causing bacterial gastroenteritis throughout the
Erasmus MC, University Medical Centre Rotterdam,
world [1–3]. The symptoms of campylobacteriosis include Rotterdam, The Netherlands
watery to 5
Fondation Mérieux, Lyon, France
bloody diarrhea, abdominal complaints, headache, and
fever [2, 4]. Furthermore, long-term sequelae have been
* Z. Islam
associated with C. jejuni infection, including Guillain–
zislam@icddrb.org
Barré syndrome
1 (GBS) [5], reactive arthritis [6], and irritable bowel
Laboratory Sciences and Services Division, International Centre syndrome (IBS) [7]. Early structure analysis revealed
for
capsule polysaccharide (CPS) in Campylobacter species [8,
Diarrhoeal Disease Research (icddr,b), GPO Box-128, Dhaka
1000, Bangladesh 9], which was further evident by a genomic study in C.
2 jejuni [10]. CPS of C. jejuni is a potent component that
Nutrition and Clinical Services Division, International Centre for
724
modulates the invasion of intestinal epithelial cells [11,
12]. This gave rise to the idea to develop a globally
relevant capsule-conjugated vaccine to prevent
campylobacteriosis [13]. The epidemiology of the global
burden of enteritis in children aged 5 years or younger,
caused by Campylobacter infection, varies geographically
[14]. Lowincome countries such as Bangladesh have a high
burden of pediatric diarrheal disease, with the higher
incidence rates of child mortality than the developed world
[15]. Contaminated water supplies, inadequate sanitation,
and nutritional deficiency contribute to this high disease
burden [16]. CPS-based vaccines are a viable strategy to
prevent diarrheal disease [17]. For optimal efficacy, the
most prevalent CPS types should be included in such a
vaccine. Therefore, epidemiological data concerning
regionally circulating C. jejuni capsule types in restricted
geographical areas where vaccination is most needed are of
crucial importance.
The CPS biosynthesis locus is a highly variable region
in the genome of C. jejuni, plays an important role in
bacterial survival and persistence in the environment, and
often contributes to pathogenesis [18]. Diversity in gene
content and gene function, combined with the presence of
phase variable genes in the capsule locus, allows the
production of a broad repertoire of capsular structures [19].
The CPS is the main serodeterminant of the Penner HS
serotyping scheme. As of now, 47 different HS serotypes
have been described [20, 21]. Unfortunately, the usefulness
of this typing method has been declining due tothe
complexity and high costs ofthe C. jejunispecific typing
antisera in recent years [22]. Recently, a multiplex
polymerase chain reaction (PCR) methodology has been
successfully developed in order to gain information on the
C. jejuni CPS distribution worldwide [23].
The Global Enteric Multicenter Study (GEMS) was
created to bridge knowledge gaps regarding diarrheal
disease in young children in sub-Saharan Africa and South
Asian countries, including Bangladesh [24, 25]. The
GEMS study showed that Campylobacter infections were a
main cause of severe diarrhea and associated with reduced
linear growth in young children in Bangladesh and Peru.
These findings underscore the need for a vaccine against
Campylobacter in these countries [26]. The lack of
available data on the distribution of C. jejuni HS serotypes
or CPS types among the Bangladeshi population
highlighted the importance of studying the geographical
distribution of CPS types [13, 27]. Therefore, we aimed to
determine the distribution of CPS types of C. jejuni strains
isolated from patients with diarrhea and from a control
population in Bangladesh. The lipooligosaccharide (LOS)
locus class was also determined because it was recently
Eur J Clin Microbiol Infect Dis (2018) 37:723–728
demonstrated that LOS loci associated with the
development of GBS frequently co-occur with particular
CPS types [20].
Methodology
Bacterial strains and growth
As a part of the GEMS, a systematic case–control study
was carried out from 2008 to 2010 in the Kumudini
Hospital at Mirzapur among children between 0 and 59
months of age living in the Mirzapur sub-district of
Bangladesh [25]. Inclusion criteria for enteritis patients
(cases) and controls (asymptomatic carriers) were
described in our earlier paper [25]. A total of 367 C. jejuni
strains were isolated from enteritis patients (n = 152) and
controls (n = 215) at the Clinical Microbiology Laboratory,
International Centre for Diarrhoeal Disease Research,
Bangladesh (icddr,b). These strains were further
characterized on the basis of their CPS genotype and LOS
locus class. We also included 30 C. jejuni strains isolated
from the stools of patients with
GBS in this study. The LOS class and CPS genotype of
these strains was reportedpreviously [20].All isolates were
cultured and identified to the genus and species levels as
previously described [28]. All strains were stored at − 80
°C in 15% glycerol in brain heart infusion broth until
testing. C. jejuni were grown on blood agar plates
containing 5% sheep blood, at 37 °C for 48 h under micro-
aerobic conditions, with 6% O2, 7% CO2, 80% N2, and 7%
H2 using the Anoxomat system (Anoxomat™ Mark II,
Drachten, the Netherlands).
Bacterial DNA isolation
Genomic DNA was isolated with the Qiagen Genomic
DNA
Purification Kit, according to the manufacturer’s
instructions (Qiagen, USA).
Multiplex PCR for CPS typing
CPS typing was performed using a multiplex PCR method;
four multiplexed mixes designated as alpha, beta, gamma,
and delta were run [23]. With this PCR method, a total of
37 CPS types can beidentified. The alpha mix is able to
detect the CPS types HS2, HS3 complex, HS4A, HS6/7,
HS10, HS19, HS15, HS41, HS53, HS63, and HS33/35.
The beta mix can detect HS1, HS4B (including HS16 and
HS64), HS12, HS8/17, HS21, HS23/36, HS5/31, HS42,
HS57, and HS27. The gamma mix can detect HS22, HS37,
HS9, HS18, HS44, HS45, HS29, and HS18. The delta mix assigned to 22 CPS types. Comparable with the results for
can detect HS11, HS60, HS32, HS58, HS40, HS55, HS52, the enteritis-associated strains, the dominant CPS types
and HS32 [20, 23]. were HS5/31 (n = 41, 19%), HS3 (n = 24, 11.2%), and
HS4A (n =
Determination of the LOS locus class 16, 7.4%). Other frequently found CPS were HS8/17 (n =
15, 7%), HS9 (n = 9, 4.2%), HS6/7 (n = 12, 5.6%), HS42
To determine the LOS class in C. jejuni strains, we used (n = 8, 3.7%), and HS1 and HS1/44 (n = 7, 3.3%). No
specific primer sets for the classes A to E, based on the significant differences in CPS types were found between
DNA sequence of genes unique to the respective LOS enteritisassociated strains and controls.
locus class(es); the primer sequences were described LOS locus class diversity
previously [29]. To discern between classes A and B, we
used specific primers that anneal to the DNA sequence of The results presented in Table 2 show that an LOS class
orf5-II [29, 30]. A–E could be assigned to 258/367 (70.3%) of the C. jejuni
strains: enteritis 103/152 (67.8%) and controls 155/215
Statistical analyses (72%). Sialylated LOS classes (A or B) were more often
identified in strains isolated from controls than in enteritis
Differences in the frequency of various CPS types between
patients (61.9% vs. 49.3%, p < 0.05). LOS class C was
cases and controls were tested with the Chi 2-test or with
identified only twice in enteritis-associated strains and in
the Fisher’s exact test. Two-tailed tests were used
one strain isolated from a control. The prevalence of LOS
throughout and p < 0.05 was regarded as statistically
locus class E was 28/ 152 (16.4%) in enteritis-associated
significant. Statistical analysis was performed using Epi
strains and 22/215 (10.3%) in controls. No LOS class D
Info version 3.5.1 and SPSS for Windows v.17 (SPSS Inc.,
was found in strains isolated from patients with enteritis or
Chicago, IL, USA).
Eur J Clin Microbiol Infect Dis (2018) 37:723–728 725
Results
controls.
Distribution of CPS types of C. jejuni isolated from
young enteritis patients and controls CPS genotypes Correlation of sialylated LOS classes and specific CPS types
were identified for 280/367 (78%) C. jejuni isolates from
In the enteritis strains with LOS class B, the dominant CPS
patients with enteritis and controls. In the enteritis-
types were HS4A (n = 11, 16.1%), HS5/31 (7, 10.2%),
associated strains, a CPS genotype could be assigned for
HS10 (n = 5, 7.4%), and HS1 (n = 5, 7.4%). In strains
119/152 (78.3%). The results are summarized in Table 1.
isolated from controls, C. jejuni with LOS class A were
Forty-seven strains in the enteritis group failed to produce
frequently typed as HS3 (n = 4, 25%)and strainswith LOS
amplicons. A wide spectrum of 24 different capsular types
class B asHS5/31 (n =
was identified, of which two capsular types, HS5/31 (n =
27, 17.8%) and HS3 (n = 26, 17.1%), were dominant. 16, 14%), followed by HS4A (n = 14, 12.2%), HS8/17 (n =
Other frequent CPS types were HS4A (n = 10, 6.6%), 6,
HS8/17 (n = 10, 5.2%), HS42 (n = 6, 5.2%), and HS3 (n = 6, 5.2%).
6.6%), HS1 and HS1/44 (n = 8, 5.3%), and HS6/7 (n = 7, Recently,
4.6%). In controls, a total of 161/215 (74.4%) could be
Table 1 Capsular polysaccharide (CPS) distribution in Campylobacter jejuni isolated from enteritis patients and controls
Controls (n =
CPS types Enteritis (n = 152)
215)
HS1 and HS1/44 8 (5.3%) 7 (3.3%)
HS2 4 (2.6%) 3 (1.4%)
HS3 (including HS13) 26 (17.1%) 24 (11.2%)
HS4A 10 (6.6%) 16 (7.4%)
HS6 and HS7 7 (4.6%) 12 (5.6%)
HS8 and HS17 10 (6.6%) 15 (7%)
HS9 1 (0.66%) 9 (4.2%)
HS10 5 (3.3%) 4 (1.9%)
726 Eur J Clin Microbiol Infect Dis (2018) 37:723–728
HS11 3 (2%) 0
HS5 and HS31 27 (17.8%) 41 (19%)
HS18 2 (1.3%) 5 (1.9%)
HS19 0 0
HS22 1 (0.7%) 3 (0.9%)
HS23 and HS36 and HS23/36 3 (2%) 5 (2.3%)
HS37 2 (1.3%) 0
HS40 2 (1.3%) 0
HS41 0 0
HS42 4 (2.6%) 8 (3.7%)
HS44 1 (0.7%) 0
HS52 1 (0.7%) 2 (0.9%)
HS53 2 (1.3%) 3 (1.4%)
HS55 0 2 (0.9%)
Untypeable
we reported the LOS class and CPS genotype of C. jejuni strains isolated from patients with GBS in Bangladesh [20]. A
striking difference in the CPS type was found when the GBS-related C. jejuni strains were compared to the strains isolated
from the stools of young children with enteritis and controls. The capsular types HS41 (6/30 vs. 1/367; p = 0.0001), HS19
(5/30 vs. 0/367; p = 0.0001), and HS23/36 (10/30 vs. 2/367; p = 0.0001) were significantly more prevalent in the GBS-
related strains compared to the strains isolated from the young children in Bangladesh (Fig. 1).

Discussion
A multivalent capsule conjugate vaccine is our best bet at remedying campylobacteriosis [27], one of the many health

Table 2 Lipooligosaccharide (LOS) class distribution in enteritis patients and controls

Controls (n =
LOS locus class Enteritis (n = 152)
215)
A 5 (3.1%) 16 (7.4%)
B 68 (39.8%) 115 (53.4%)
C 2 (1.8%) 2 (1%)
D 0 0
E 28 (16.4%) 22 (10.3%)
NT 49 (28.9%) 60 (28%)
p-Value enteritis vs. controls
Fig. 1 Relation between capsule
polysaccharide (CPS) genotype
and lipooligosaccharide (LOS)
classes in Campylobacter jejuni in
young enteritis patients, controls,
and patients with Guillain–Barré
syndrome (GBS)
consequences of C. jejuni infection worldwide, especially
in the younger population of developing nations [25, 31].
Many prevalence studies were conducted in Europe,
whereas there are very few data available from the
developing countries, despite C. jejuni infection’s
significant contribution to morbidity and mortality in both
[22]. In order to obtain sufficient data from a low-income
country, we determined the distribution of CPS genotype
and LOS class of C. jejuni strains isolated from patients
with enteritis as well as controls in Bangladesh, where
diarrheal disease is endemic and vaccination key to
lessening the disease burden. We identified the capsular
types HS5/31, HS3 complex, HS4A, HS8/17, and HS6/7 as
the dominant types for C. jejuni-associated strains isolated
from both enteritis patients and controls, and failed to see
any significant correlation between CPS types and LOS
classes.
The present study revealed that the capsule type HS5/31
(18.5%) and HS3 (13.6%) are the two most prevalent CPS
Eur J Clin Microbiol Infect Dis (2018) 37:723–728
types in Bangladesh; surprisingly, they represent only 2.9%
and 2.2%, respectively, in the global picture [22]. Other
prevalent CPS types in enteritis strains isolated from
patients and controls in Bangladesh wereHS4A, HS8/17,
HS1, and HS6/7. Globally, the most dominant CPS types
are HS1, HS2, and HS4 complex (HS4A and HS4B),
making up to 50% of the strains, followed by HS11,
HS5/31, HS8/17, HS6/7, and HS3, cumulatively
comprising up to 70% of the strains [22], which is not the
case in Bangladesh. Such a differing order of prevalence
suggests that a multivalent vaccine containing a
combination of these handpicked CPS types can provide
protection to only patients in a certain geographical region,
but is far away from being a remedy against diarrhea for
other parts of the world. Since the data on CPS typing from
other developing nations is insufficient, we need extensive
surveillance from these nations to corroborate our findings.
This needs to be done prior to regional implementation of
any CPS-based vaccine and there should be continuous
monitoring for CPS endemicity changes over time.
While a Dutch study recently reported HS1/44c, HS2, or
HS4c as the prevalent CPS types among GBS-associated
strains from the Netherlands [20], in Bangladesh, HS23/36,
HS41, and HS19 were the dominant CPS types in
GBSrelated strains [20, 32].Interestingly, in the current
study, these capsular types were mostly absent in strains
isolated from young enteritis patients and controls. The
difference could be due to the fact that GBS patients are
usually not restricted to any particular age group or, more
likely, to geographic and/ or temporal differences in CPS
type endemicity. Apparently, young children in
Bangladesh are infected with or are asymptomatic carriers
of C. jejuni strains with other capsular types compared to
patients with GBS. Other studies revealed that the capsular
serotypes HS19, HS23/36, and HS41 were overrepresented
among GBS patients in Japan and South Africa,
respectively [32–34]. A wide range of CPS types including
HS1, HS2, HS4, HS5, HS10, HS16, HS23, HS37, HS44,
and HS64 is usually identified in C. jejuni strains isolated
from GBS patients in high-income countries. TheseCPS
types are also commonly found in enteritis-associated
strains derived from patients in many different countries
[35–40].
C. jejunisialylatedLOS, encodedbytheLOSlociclassesA,
B, and C, is the most widely accepted virulence factor
instigating GBS [41]. Parker et al. reported that 100% of
GBSassociated strains had LOS classes A, B, or C
compared to only 64% of the other clinical and
environmental isolates [30]. Our study reports a slightly
727
lower percentage for C. jejuni strains isolated from enteritis
patients (44.7%) and a similar percentage of C. jejuni
strains from controls (61.9%). When comparing LOS
classification with capsular genotyping in
enteritisassociated strains, no genetic linkage was evident,
unlike the striking genetic correlation found between the
two in GBSassociated strains in previous studies [20, 32,
36], a correlation attributed to the genes shared by LOS
and capsules [19].
The fact that a large portion (24.7%) of the 367 isolates
collectedinourstudywere‘non-typeable’couldbeduetonovel
capsulesasyetunclassifiedbythePennerserotyping method,or
capsules that were not yet included in the multiplex PCR.
New primers specific for yet undiscovered genes in the
gene pool could be introduced in the multiplex PCR to
overcome this limitation. Prior studies conducted in
developed countries indicate that only eight CPS types
make up over two-thirds of the C. jejuni CPS types, but
none of them make the list of even the top 5 most prevalent
capsular genotypes found in Bangladesh. Therefore,
multivalency is required for an effective C. jejuni
conjugate vaccine, targeting the commonest and most
pathogenic CPS types circulating in particular regions
where the inhabitants are in dire need of vaccines.
Considering this highincidence rate,the potentialbenefit
of a future vaccine is greatest in the developing world.
Therefore, continued search of such a strategy will require
answering questions about the required valency of a
broadly effective CPS conjugate vaccine against C. jejuni.
Implementation of sucha surveillance program will require
728
a commitmentoftime and resources that has not been
provided to date.
Acknowledgements This research study was funded by icddr,b's core
donors through mentoring program. icddr,b also gratefully
acknowledges the following donors who provide unrestricted
support: the Government of the People's Republic of Bangladesh,
Global Affairs Canada (GAC), Swedish International Development
Cooperation Agency (Sida), and the Department for International
Development (UK Aid).
Compliance with Ethical Standards
Conflict of Interest The funders had no role in the study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. The authors declare that they have no conflict of interest.
References
1. Allos BM (2001) Campylobacter jejuni infections: update on
emerging issues and trends. Clin Infect Dis 32(8):1201–1206
2. Butzler JP (2004) Campylobacter, from obscurity to celebrity.
Clin Microbiol Infect 10(10):868–876
3. Humphrey T, O’Brien S, Madsen M (2007) Campylobacters as
zoonotic pathogens: a food production perspective. Int J Food
Microbiol 117(3):237–257
4. Mills DC, Gundogdu O, Elmi A et al (2012) Increase in
Campylobacter jejuni invasion of intestinal epithelial cells
under low-oxygen coculture conditions that reflect the in vivo
environment. Infect Immun 80(5):1690–1698
5. Ang CW, Jacobs BC, Laman JD (2004) The Guillain–Barré
syndrome: a true case of molecular mimicry. Trends Immunol
25(2):61–66
6. Pope JE, Krizova A, Garg AX, Thiessen-Philbrook H, Ouimet
JM (2007) Campylobacter reactive arthritis: a systematic
review. Semin Arthritis Rheum 37(1):48–55
7. Thabane M, Simunovic M, Akhtar-Danesh N et al (2010) An
outbreak of acute bacterial gastroenteritis is associated with an
increased incidence of irritable bowel syndrome in children.
Am J Gastroenterol 105(4):933–939
8. Aspinall GD, McDonald AG, Pang H, Kurjanczyk LA, Penner
JL (1993) An antigenic polysaccharide from Campylobacter
coli serotype O:30. Structure of a teichoic acid-like antigenic
polysaccharide associated with the lipopolysaccharide. J Biol
Chem 268(24): 18321–18329
9. Aspinall GO, Lynch CM, Pang H, Shaver RT, Moran AP
(1995) Chemical structures of the core region of
Campylobacter jejuni O:3 lipopolysaccharide and an associated
polysaccharide. Eur J Biochem 231(3):570–578
10. Parkhill J, Wren BW, Mungall K et al (2000) The genome
sequence of the food-borne pathogen Campylobacter jejuni
reveals hypervariable sequences. Nature 403(6770):665–668
11. Bachtiar BM, Coloe PJ, Fry BN (2007) Knockout mutagenesis
of the kpsE gene of Campylobacter jejuni 81116 and its
involvement in bacterium–host interactions. FEMS Immunol
Med Microbiol 49(1):149–154
12. Bacon DJ, Szymanski CM, Burr DH, Silver RP, Alm RA,
Guerry P (2001) A phase-variable capsule is involved in
Eur J Clin Microbiol Infect Dis (2018) 37:723–728
virulence of Campylobacter jejuni 81-176. Mol Microbiol
40(3):769–777
13. Guerry P, Poly F, Riddle M, Maue AC, Chen YH, Monteiro
MA
(2012) Campylobacter polysaccharide capsules: virulence and
vaccines. Front Cell Infect Microbiol 2:7
14. Murray CJ, Vos T, Lozano R et al (2012) Disability-adjusted
life years (DALYs) for 291 diseases and injuries in 21 regions,
1990– 2010: a systematic analysis for the Global Burden of
Disease Study 2010. Lancet 380(9859):2197–2223
15. Walker CLF, Perin J, Aryee MJ, Boschi-Pinto C, Black RE
(2012) Diarrhea incidence in low- and middle-income countries
in 1990 and 2010: a systematic review. BMC Public Health
12(1):220
16. Lamberti LM, Fischer Walker CL, Noiman A, Victora C, Black
RE (2011) Breastfeeding and the risk for diarrhea morbidity
and mortality. BMC Public Health 11(Suppl 3):S15
17. Maue AC, Poly F, Guerry P (2014) A capsule conjugate
vaccine approach to prevent diarrheal disease caused by
Campylobacter jejuni. Hum Vaccin Immunother 10(6):1499–
1504
18. Roberts IS (1996) The biochemistry and genetics of capsular
polysaccharide production in bacteria. Annu Rev Microbiol
50(1):285–315
19. Karlyshev AV, Champion OL, Churcher C et al (2005)
Analysis of Campylobacter jejuni capsular loci reveals multiple
mechanisms for the generation of structural diversity and the
ability to form complex heptoses. Mol Microbiol 55(1):90–103
20. Heikema AP, Islam Z, Horst-Kreft D et al (2015)
Campylobacter jejuni capsular genotypes are related to
Guillain–Barré syndrome. Clin Microbiol Infect 21(9):852.e1–
852.e9
21. Penner JL, Hennessy JN, Congi RV (1983) Serotyping of
Campylobacter jejuni and Campylobacter coli on the basis of
thermostable antigens. Eur J Clin Microbiol 2(4):378–383
22. Pike BL, Guerry P, Poly F (2013) Global distribution of
Campylobacter jejuni Penner serotypes: a systematic review.
PLoS One 8(6):e67375
23. Poly F, Serichatalergs O, Schulman M et al (2011)
Discrimination of major capsular types of Campylobacter jejuni
by multiplex PCR. J Clin Microbiol 49(5):1750–1757
24. Kotloff KL, Blackwelder WC, Nasrin D et al (2012) The
Global Enteric Multicenter Study (GEMS) of diarrheal disease
in infants and young children in developing countries:
epidemiologic and clinical methods of the case/control study.
Clin Infect Dis 55(Suppl 4):S232–S245
25. Kotloff KL, Nataro JP, Blackwelder WC et al (2013) Burden
and aetiology of diarrhoeal disease in infants and young
children in developing countries (the Global Enteric
Multicenter Study, GEMS): a prospective, case–control study.
Lancet 382(9888): 209–222
26. Levine MM, Kotloff KL, Nataro JP, Muhsen K (2012) The
Global Enteric Multicenter Study (GEMS): impetus, rationale,
and genesis. Clin Infect Dis 55(Suppl 4):S215–S224
27. Bertolo L, Ewing CP, Maue A, Poly F, Guerry P, Monteiro MA
(2013) The design of a capsule polysaccharide conjugate
vaccine against Campylobacter jejuni serotype HS15.
Carbohydr Res 366: 45–49
28. Talukder KA, Aslam M, Islam Z et al (2008) Prevalence of
virulence genes and cytolethal distending toxin production in
Campylobacter jejuni isolates from diarrheal patients in
Bangladesh. J Clin Microbiol 46(4):1485–1488
29. Godschalk PC, Heikema AP, Gilbert M et al (2004) The crucial
role of Campylobacter jejuni genes in anti-ganglioside antibody
induction in Guillain–Barre syndrome. J Clin Invest
114(11):1659–1665
30. Parker CT, Horn ST, Gilbert M, Miller WG, Woodward DL,
Mandrell RE (2005) Comparison of Campylobacter jejuni
lipooligosaccharide biosynthesis loci from a variety of sources.
J Clin Microbiol 43(6):2771–2781
31. Chandra Mouli Natchu U, Bhatnagar S (2013) Diarrhoea in
children: identifying the cause and burden. Lancet
382(9888):184–186
32. Islam Z, van Belkum A, Cody AJ et al (2009) Campylobacter
jejuni HS:23 and Guillain–Barre syndrome, Bangladesh. Emerg
Infect Dis 15(8):1315–1317
33. Kuroki S, Saida T, Nukina M et al (1993) Campylobacter jejuni
strains from patients with Guillain–Barré syndrome belong
mostly
to Penner serogroup 19 and contain beta-N-acetylglucosamine
residues. Ann Neurol 33(3):243–247
34. Lastovica AJ, Goddard EA, Argent AC (1997) Guillain–Barré
syndrome in South Africa associated with Campylobacter
jejuni O:41 strains. J Infect Dis 176(Suppl 2):S139–S143
35. Endtz HP, Ang CW, van Den Braak N et al (2000) Molecular
characterization of Campylobacter jejuni from patients with
Guillain–Barré and Miller Fisher syndromes. J Clin Microbiol
38(6):2297–2301
36. Nachamkin I, Engberg J, Gutacker M et al (2001) Molecular
population genetic analysis of Campylobacter jejuni HS:19
associated with Guillain–Barré syndrome and gastroenteritis. J
Infect Dis 184(2):221–226
37. Rees JH, Soudain SE, Gregson NA, Hughes RA (1995)
Campylobacter jejuni infection and Guillain–Barré syndrome.
N Engl J Med 333(21):1374–1379
38. Jacobs BC, Endtz H, van der Meché FG, Hazenberg MP,
Achtereekte HA, van Doorn PA (1995) Serum anti-GQ1b IgG
antibodies recognize surface epitopes on Campylobacter jejuni
from patients with Miller Fisher syndrome. Ann Neurol 37(2):
260–264
39. Yuki N (1997) Molecular mimicry between gangliosides and
lipopolysaccharides of Campylobacter jejuni isolated from
patients with Guillain–Barré syndrome and Miller Fisher
syndrome. J Infect Dis 176(Suppl 2):S150–S153
40. Sheikh KA, Ho TW, Nachamkin I et al (1998) Molecular
mimicry in Guillain–Barré syndrome. Ann N Y Acad Sci
845:307–321
41. Godschalk PC, Heikema AP, Gilbert M et al (2004) The crucial
role of Campylobacter jejuni genes in anti-ganglioside antibody
induction in Guillain–Barré syndrome. J Clin Invest
114(11):1659–1665
European Journal of Clinical Microbiology & Infectious Diseases is a copyright of Springer,
2018. All Rights Reserved.