Journal of Infection and Public Health 10 (2017) 814–818

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Journal of Infection and Public Health

j o u r n a l h o me p a g e : h t t p : / / w w w . e l s e v i e r . c o m / l o c a t e / j i p h

An outbreak of shigellosis in a Children Welfare Institute caused by a

multiple-antibiotic-resistant strain of Shigella flexneri 2a
Hongwei Shen a,1 , Jian Chen a,1 , Yucheng Xu a , Zhifa Lai a , Jinjin Zhang a , Hong Yang b ,
Yinghui Li c , Min Jiang c , Yuhui Ye b , Xiangning Bai d,∗
a Futian District Center for Disease Control and Prevention, Shenzhen, Guangdong, China
b Microbiological Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China,
c
Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
d
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center
for Disease Control and Prevention, Beijing, China

a rt i c le i n f o ab s tr ac t

Article history: From September 1 to October 27, 2015, an outbreak of bacillary dysentery occurred in the Shenzhen
Received 30 June 2016 Children Welfare Institute (SCWI). The shigellosis was uncommon in Shenzhen and no related outbreak
Received in revised form 6 December 2016 was reported during the last 5 years. An epidemiological investigation was conducted and the children
Accepted 7 January 2017
and nursing workers in SCWI were surveyed for gastrointestinal symptoms; 28 of children reported
having a diarrheal illness. Rectal swabs or fecal specimens from 14 case patients and 24 nursing workers
Keywords:
or cook, as well as 17 swabs from implicated items were collected and examined for Shigella, Vibrio
Outbreak
parahaemolyticus, and Salmonella. Susceptibility testing and pulse-field gel electrophoresis (PFGE) were
Shigellosis
Children Welfare Institute performed on the Shigella isolates.
Multiple-antibiotic-resistant The multiple-antibiotic-resistant Shigella flexneri 2a was isolated from 10 ill children aged less than 5
Shigella flexneri 2a years. The source of the outbreak was most likely a new welfare child transferred from an institute in
anothercounty and the secondary transmission of the illness was facilitated by the limited activity space
and thecohabiting of ill and well residents. The outbreak was controlled after quarantine of ill residents,
introduction of new antibiotics and the improvements of hygienic condition. This was the first time
that shigellosis outbreak was reported at such settings in Shenzhen and the results of this investigation
underscored theneed for adequate precautions to prevent secondary transmissionof multiple-antibiotic-
resistant strain in the welfare setting.
© 2017 The Authors. Published by Elsevier Limited. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction of Shigella is low, and it is easy to cause outbreak through con-

Shigellosis or bacillary dysentery is one of the major causes of
morbidity and mortality in children with diarrhea in developing
countries [1]. In China, Shigella spp.is one of the mostfrequently iso-
lated enteric pathogens accounting for up to 1.7 million episodesof
bacillary dysentery per year [2,3]. The infections are caused mostly
by Shigella flexneri and Shigella sonnei, with variant X and 2a being
reported as the most prevalent serotypes of S. flexneri [4]. Isolates
recovered from patients with diarrhea show a high frequency of
antibiotic resistance in most areas of China [5–8], posing great
treatment and controlling problems. In addition, the infection dose
∗ Corresponding author at: Changbai Road 155, Changping District, Beijing,
102206, China.
E-mail address: baixiangning@icdc.cn (X. Bai).
1 These authors have contributed equally to this work.
taminated food or personal contact, particularly in settings where
hygiene is inherently poor [2,4,7,9].
However, large regional differences could be observed due
to the differences in the climate, diet, economic and healthcare
development in different cities of China [2,10–12]. Only several
sporadic cases were identified annually in the sentinel hospital-
based surveillancenetwork in Shenzhen and a decreasing incidence
rate was seen since 2014 [13]. No shigellosis outbreak had been
reported in Shenzhen for more than 5 years. In this investigation,
a possible mode of introduction of multiple-antibiotic-resistant
strains of Shigella into Shenzhen was suggested.
We report here the first shigellosis outbreak in SCWI, a resi-
dential facility and custodial institution for the mentally retarded
in Shenzhen. The outbreak involved 28 children aged less than 5
years who were developmentally disabled. A deserted child from a
county of Anhui where the multiple-antibiotic-resistant S. flexneri

http://dx.doi.org/10.1016/j.jiph.2017.01.003
1876-0341/© 2017 The Authors. Published by Elsevier Limited. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/ ).
 H. Shen et al. / Journal of Infection and Public Health 10 (2017) 814–818
was endemic was likely responsible for this outbreak. The over-
crowding, poor ventilation and malnutrition may facilitate the
spread of infectious strains. After the interventions were imple-
mented, the outbreak was taken under control effectively.
Background
From September 1st through October 27th, 2015, 28 children
in SCWI experienced severe gastrointestinal illness. This outbreak
was reported to Futian District Center for Disease Control and Pre-
vention, Shenzhen (Futian CDC) on October 13th and weconducted
the investigation from October 14th. After stool or rectal swab cul-
tures from patients revealed S. flexneri, the probable transmission
route wasinvestigated and comprehensive measures wereadopted
to control the outbreak. This article describes the findings of our
investigation to characterize the magnitude and source, as well as
the controlling of this outbreak.
Materials and methods
Outbreak investigation
Acase patient was defined as acute diarrhea (three ormore loose
or liquid stools in a 24-h period) and one other symptom (vomit-
ing, fever, and erythrocytes, leukocytes or phagocytes in the stool)
since August 23rd. Standardized questionnaires requesting infor-
mation about demographics, food histories, daily activities, signs
and symptoms of illness, health status, as well as use of antibiotics
or other medications were collected from the nursing workers.
SCWI houses 102 mentally retarded children and most of them
are permanent residents of the facility; 90% are <5 years old. There
are 3 baby rooms on the 3rd floor, 5 general wards and 3 isolation
wardson the 4th floor, andthree observationrooms on the 6th floor.
Within each room, residents live in separate toddler beds where
they sleep and spend their leisure time and their daily lives are
looked after by2 nursingworkers every 6 h. Diarrheal patientswere
given 50mg/kg per day of ceftriaxone divided in 2 equal doses for
treatment of diarrhea. The therapy was stopped after the patient’s
condition improved clinically.
Initially, 7 rectal swabs from diarrheal children and 5 swabs
from implicated items (see below) were collected on October 14th.
After S. flexneri isolates were recovered from 5 out of the 7 rectal
swabs, asecond batch of stool or rectal swabs were collected fromill
children (n = 7) whose onset of diarrhea occurred between October
15th and October 20th. Furthermore, 12 swabs from implicated
items and 24 stool samples from nursing workers and cook were
also collected. Based on the findings of the investigation, the isola-
tion of infected persons along with diarrhea surveillance, improved
personal hygiene, living environment and new antibiotics were
implemented, and no further cases were reported after October
20th.
Laboratory investigation
The stool specimens orrectal swabs obtainedfrom the14 ill chil-
dren and 24 nursing workers and cook were examined for Shigella,
Vibrio parahemolyticus, and Salmonella at Futian CDC, using xylose
lysine desoxycholate (XLD) agar media and CHROM agars, respec-
tively. The swabs from 17 implicated items were enriched and
then cultured for Shigella using XLD agar, which included feed-
ing bottles, swivels, bathtubs, towels, gloves, and tables used for
diaper-changing. All the Shigella isolates were identified using the
Sensititre GNID (TREK Diagnostic System, Cleveland, OH, USA) and
serotyped with a commercial serotyping kit (Denka Seiken, Tokyo,
815
Japan) according to the manufacturer’s instructions, followed by
the susceptibility testing using the VITEK 2 system.
In addition, pulse-field gel electrophoresis (PFGE) was per-
formed on the S. flexneri isolates on Not I (New England BioLabs,
Ipswich, Mass) chromosomal DNA digests. The fragments were
separated using a contour-clamped homogeneous electric field
(CHEF-Mapper) apparatus (BIO-RAD, Hercules, CA), and the gel
images were analyzed using BioNumerics software program.
Ethical approval
All aspects of this study were performed in accordance with
national ethics regulations and approved by the Ethics Committee
of Futian CDC. The children’s guardians received written infor-
mation regarding the purpose of this study and of their right to
confidentiality. Written consent was obtained from the director of
this institute.
Results
Epidemiologic investigation
A 1 year and 4months old boy (ChildA) transferred from another
welfare institute on August 26th with mild symptom of diarrhea
and was kept in an observation room (Room 1), he then presented
with diarrhea with bloody mucopurulent stool on September 1st.
Child A was treated with ceftriaxone for the diarrhea after onset
of illness, but his symptom recurred during August 26th and
September 28th while hewas kept at Room 1 (Fig. 1). He was then
transferred to a baby room (Room 2) after the symptom disap-
peared and stayed there from September 29th through October5th
(Fig. 1), and most of the diarrheal illnesses occurred subsequently in
Room 2. This child reported diarrhea again on September 30th and
the onset of diarrhea among other 17 children living in this room
occurred between October 9th and October 19th. Then Child A was
transferred to an isolation ward (Room 3), which was assigned to
receive and treat the severe diarrheal patients from Room 1 and
Room 2, on October 6th (Fig. 1). Another three children who were
kept at this isolated area due to other diseases developed diarrhea
during October 16th and October 20th (Fig. 1).
Twenty-eight (27%) of 102 welfare children were reported hav-
ing diarrhea; 12 (43%) were male. Seven of 17, eighteen of 19, and
three of 11 children met the case definition in Room 1, Room 2 and
Room 3, respectively. There was no case reported at other rooms
on each floor. All the patients were aged between 3 months and 3
years and 4 months old, with the mean age of 1.5 years old. Diar-
rhea was the most common reported symptom, followed by fever,
leukocytes, erythrocytes and phagocytes in the stool (Table 1).
Ill and well children were similar in age and sex distribution,
water and food supply, butdiffered in the bed location. All the cases
were distributed at three rooms where Child A had stayed and the
onset of their symptoms occurred after staying at the same room
with Child A. No caseswere reported at other rooms nor among the
nursing workers and cook. No deaths were reported.
Table 1
The clinical manifestations and routine test results of stool samples of the 28 diar-
rheal patients.
Symptoms No. of cases (%)
Diarrhea 28 (100.0)
Fever 18 (64.3)
Leukocytesin the stool 16 (57.1)
Erythrocytes in the stool 13 (46.4)
Phagocytes in the stool 3 (10.7)
816 H. Shen et al. / Journal of Infection and Public Health 10 (2017) 814–818

Fig. 1. Cases of shigellosis by onset of diarrhea among institutionalized children in SCWI, 2015.

Table 2 ers with diarrhea, encourage appropriate hand-washing hygiene

MICs for S. flexneri isolatesrecovered from 10 diarrheal children in SCWI, 2015.
among the nursingworkers, transfer the ill children toisolated area,
Antimicrobial agent MIC ( g/ml) for Antimicrobial MIC ( g/ml) for provide enough feeding bottles for children, and report daily to the
10 isolatesa agent 10 isolatesa Futian CDC. After Shigella was identified in ill children, the Futian
Ampicillin ≥32 Aztreonam ≥64 CDC recommended that all nursing workers and cooks submit a
Ampicillin/sulbactam ≥32 Imipenem ≤1 stool specimen for culture andcollecting swabs fromthe implicated
Piperacillin ≥128 Meropenem ≤0.25 items. The more comprehensive measures were implemented,
Piperacillin/tazobactam ≤4 Amikacin ≤2
Cefazolin ≥64 Gentamicin ≤1
including isolation of infected persons, hygienic management of
Cefuroxime-sodium ≥64 Tobramycin ≤1 food and water, better ventilation condition, propaganda of health
Cefuroxime-axetil ≥64 Ciprofloxacin ≥4 knowledge, disinfection of the feeding bottles, and one-week med-
Cefotetan ≤4 Levofloxacin 4 ical observation for those of close contacts.
Ceftazidime 16 Nitrofurantoin ≤16
When the antibiogram of the Shigella strain was identified, the
Ceftriaxone ≥64 Trimethoprim/sulfa ≥320
Cefepimeb 16–≥64 patients were treated with amikacin and imipenem to which the
a The no. of the ten isolates was Room 1-1, Room 2-1, Room 2-2, Room 2-3, Room
isolated Shigella strain was sensitive. Amikacin was administered
in single daily doses of 15 mg/kg divided into two equal doses,
2-4, Room2-5, Room 2-6, Room 2-7, Room 3-1, and Room 3-2, respectively.
b
The MIC ( g/ml) of cefepime for Room 2-2 isolate was 16; for Room 1-1, Room and imipenem 60 mg/kg per day divided into three equal doses.
2-3, Room2-6, and Room 2-7 was 32; and for other 5 isolates was ≥64. No further cases were reported after October 20th.

Laboratory results
Rectal swabs obtained from 10 out of the 14 ill children
yielded S. flexneri 2a which was resistant to ampicillin, sulbac-
tam, piperacillin, cefazolin, cefuroxime-sodium, cefuroxime-axetil,
ceftazidime, ceftriaxone, cefepime, aztreonam, ciprofloxacin, and
trimethoprim/sulfa but was sensitive to tazobactam, cefotetan,
imipenem, meropenem, amikacin, gentamicin, tobramycin, and
nitrofurantoin and was intermediate sensitive to levofloxacin
(Table 2). The rectal swabs or stool specimens received from the 24
nursing workers and cook, as well as the swabs from 17 implicated
items were all negative for Shigella.
Pulsed-field gel electrophoresis revealed that all the 10 iso-
lates were indistinguishable from each other, but differed from 2
non-outbreak isolates of S. flexneri 2a obtained from our laboratory-
based surveillance for foodborne pathogens during 2009 and 2013.
The outbreak strains differed from the non-outbreak strains by 4
and 5 bands, respectively (Fig. 2).
Control measures
At the end of the first day of the investigation, investigators
from Futian CDC recommended to the institute director that they
improve the ventilation condition at these rooms, excludeill work-
Discussion
This outbreak of gastroenteritis at SCWI was caused by a
multiple-antibiotic-resistant strain of S. flexneri 2a. Although 28
(27%) of 102 children in this institute were reported having diar-
rhea, the attacking rate was significantly higher (28 of 47) in the
three rooms in which the outbreak occurred (Room 1, Room 2
and Room 3) compared with that of other rooms. In addition, the
onset of symptoms of these ill persons occurred after they stayed
with Child A, indicating this outbreak was caused by secondary,
person-to-person spread of the Shigella, since as few as 10 Shigella
organisms can cause illness [9]. No vehicle for infection was iden-
tified, but after comprehensive measures were implemented this
outbreak was taken under control effectively.
Although shigellosis or bacillary dysentery remains one of the
major infectiousdiseases in developing countries, it mainly affects
economically poor populations and the episodes or deaths mainly
involved children aged under 5 years old [1]. The 60% of isolates in
shigellosis patients were S. flexneri and the predominant serotype
of S. flexneri is 2a in developing countries [1,8]. In addition, the
multidrug-resistant Shigella isolates were commonly observed in
China [14–17]. However, benefiting from the economic develop-
ment and progress in the health care, only a few sporadic cases
were reported each year in Shenzhen [18–20]. No case was found
in the laboratory-based surveillance for acute diarrhea in Shenzhen
 H. Shen et al. / Journal of Infection and Public Health 10 (2017) 814–818
Fig. 2. PFGE patterns from S. flexneri type 2a isolates. D15001-D15010, case isolates; D15011-D15012, non-outbreak isolates.
during August 2014 through September 2015 [13]. This outbreak
demonstrated how antibiotic-resistant strains could be introduced
into Shenzhen, where they could pose treatment and controlling
problems.
During the first investigation, we found issues of overcrowding,
poor ventilation, and the risk of cross-infection through nursing
workers. Therefore, we suggested that the corresponding improve-
ment measures should beinitiated. We also recommended that the
facility staff practice good personal hygiene which included wear-
ing gloves when changing diapers and hand washing after. As the
food and drinking water were centrally supplied but only the res-
idents of these 3 rooms reported illness, food and water seemed
unlikely to be the vehicle of infection and control measures were
not introduced.
After the S. flexneri 2a was identified, we initiated an inter-
vention program that was implemented in a shigellosis outbreak
among institutionalized persons [21]. The program included seg-
regation of ill and well residents, antibiotic therapy and supervised
hand washing for all nursing workers. The case patients were
only found at the rooms where Child A have stayed in, consis-
tentwith previous investigation that duration of diarrhea may have
increased the risk of infection for other residents within the same
unit[21]. The decrease in attack rateafter thesegregation suggested
that this measure may be useful in preventing transmission from
recovering residents to susceptible persons. The elimination of the
organism may also be attributed to appropriate antibiotic treat-
ment, which was confirmed in other investigations [21]. Although
a fewcases showed bacteriologic success after administration ofthe
antibiotics to which their isolates were resistant [22], the in vitro
antibiotics susceptibility results were still guidelines for selecting
appropriate antibiotics for treatments [23]. Guided by the antibi-
otics results, therapy was changed to amikacin and imipenem,
which resulted in therapeutic success. However, it may be diffi-
cult to differentiate the effect of antibiotic therapy from the effect
of isolation of ill residents as the two measures were implemented
simultaneously.
Multiple vehicles were identified in the outbreaks of shigellosis
caused by S. flexneri in which food(s) were implicated [4,24,25].
The secondary, person-to-person spread of the Shigella was also
reported in some outbreaks [7,26,27]. In this outbreak, the fact
that all the case patients were reported having the residential his-
817
tory with Child A at the same room, as well as overcrowding, poor
health status for some children, and our PFGE results suggested
the person-to-person mode of transmission for the widespread
infection. PFGE was a highly discriminatory typing method fordis-
tinguishing bacterial isolates and served as a useful adjunct to
epidemiological investigation [28]. Here, the PFGE results were
indistinguishable from one another for the 10 tested isolates and
differed from the non-outbreak strains, suggesting the 10 isolates
might be genetically and epidemiologically related. Moreover, the
10 isolates had quite close resistance phenotypes also indicating
they might come from the same source. In addition, the samples of
the implicated items which were available for culture and the fecal
samples from nursing workers were all tested negative for Shigella.
Therefore, the outbreak was not likely associated with food and
the nursing workers. It was the cohabiting of ill and well residents,
inappropriate antibiotic therapy, overcrowding, and malnutrition
that facilitate the spread of the transmission.
In this outbreak, the use of ceftriaxone to which the isolated
Shigella was resistant was probably associated with the prolonged
duration of illness (>10 days). The illness of Child A recurred during
September 1st–October 19th before being switched to imipenem,
suggesting that inappropriate antibiotic use could affect the out-
come of treatment. This is consistent with previous outbreak
investigation and studies in which prolonged shigellosis occurred
or hemolytic uremic syndrome or death developed when inappro-
priate antibiotics were used [4–6]. As the Shigella has demonstrated
extraordinary prowess in acquiring plasmid-encoded resistance to
antimicrobial drugs [1], clinicians should be aware of these prob-
lems when treating for diarrheal patients from counties where
multiple-antibiotic-resistant Shigella is common. Nevertheless, it
was still uncommon that shigellosis could last an unusually long
time. After excluding the HIV infection, the crowded condition
within the room and poor immune state due to the malnutrition
might also be responsible for the prolonged illness exhibited by
Child A. It was reported that the duration of diarrhea caused by
Shigella increased progressively as the nutritional status got worse
in the young children [29].
The investigation could be improved if the microbiological test-
ing had been performed for the samples from all the 28 cases.
This was because isolating and identifying the Shigella strains from
all cases would require massive laboratory work, which is beyond
818 H. Shen et al. / Journal of Infection and Public Health 10 (2017) 814–818
our working capacity. Moreover, the diarrheal diseases within this
institute were common enoughthat they could have resulted in the
observed symptoms. Therefore,we only sent rectal swabs collected
from severe or representative cases to microbiology laboratory.
The resultsof this investigation suggestedthat this outbreak was
caused by a multiple-antibiotic-resistant S. flexneri 2a strain which
was probably introduced into the SCWI by a child who came from
a county where multiple-antibiotic-resistant Shigella is endemic.
It is likely that the outbreak strain spread via a person-to-person
mode of transmission. Our resultsunderscore the need for adequate
precautions to prevent shigellosis outbreak at such settings and to
restrict the abuse of antimicrobials. Measures to reduce the risk
of such occurrences might include screening and initially isolating
such cases for treatment, isolation of infected persons, early appro-
priate antibiotictreatment, and improvements of personal hygiene
and living environment.
Acknowledgments
This work was supported by Futian District Public Health
Research Project (FTWS2015043) and Shenzhen Science and Tech-
nology Innovation Committee (JCYJ 20140415162543001). We
thank staff from Shenzhen Center for Disease Control and Pre-
vention for assistance in PFGE typing for isolates, from Peking
University Shenzhen Hospital for assistance in describing antimi-
crobial susceptibility patterns, from Futian District Center for
Disease Control and Prevention for epidemiological investigation,
and Mr. Andrew Chun Hoong Tan from the University of Manch-
ester for critical reading of this manuscript.
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