Accepted
Manuscript
Title:
Cholera in pregnancy: Clinical and immunological
Aspects
Author: Ashraful I. Khan Fahima Chowdhury Daniel T.
Leung Regina C. Larocque Jason B. Harris Edward T.
Ryan
Stephen B. Calderwood Firdausi Qadri
PII: S1201-9712(15)00201-5
DOI:
http://dx.doi.org/doi:10.1016/j.ijid.2015.08.006
Reference: IJID 2414
To appear in: International Journal of Infectious
Diseases
Received date: 5-5-2015
Revised date: 13-7-2015
Accepted date: 9-8-2015
Please cite this article as: Khan AI, Chowdhury F,
Leung DT, Larocque RC,
Harris JB, Ryan ET, Calderwood SB, Qadri F, Cholera
in pregnancy: Clinical
and immunological aspects, International Journal of
Infectious Diseases (2015),
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Highlights
Pregnant and non-pregnant women with cholera had
similar clinical severity and
comparable immune responses.
We did not observe adverse fetal outcomes in 21
days of follow up after cholera in this
cohort presenting at a median of 14 weeks of
gestation.
These data support further study of the use of
oral killed cholera vaccine in pregnant
women at risk for cholera in cholera endemic areas.
Our study was limited to individuals with severe
cholera, and immunological responses
in mild or asymptomatic cases were not evaluated in
the cohort.
Cholera in pregnancy: Clinical and immunological
aspects
Ashraful I. Khan1, Fahima Chowdhury1, Daniel T.
Leung1,6, Regina C. Larocque2,3, Jason
B. Harris2,3, Edward T. Ryan2,3,5, Stephen B. Calderwood2,3,4,
Firdausi Qadri1*.
1Centre for Vaccine Sciences, International Centre
for Diarrhoeal Disease Research, Bangladesh
(icddr,b), Dhaka, Bangladesh
2Division of Infectious Diseases, Massachusetts
General Hospital, Boston, MA, USA
3Department of Medicine, Harvard Medical School,
Boston, MA, USA
4Department of Microbiology and Immunobiology,
Harvard Medical School, Boston, MA, USA
5Department of Immunology and Infectious Diseases,
Harvard School of Public Health, Boston,
MA, USA
6Division of Infectious Diseases, University of
Utah, Salt Lake City, UT, USA
*Corresponding author at: Centre for Vaccine
Sciences, icddr,b, 68 Shahid Tajuddin Ahmed
Sarani, Mohakhali, Dhaka 1212, Bangladesh. Tel.:
+880-2-9827001-10, Ext: 2431; fax: +880 2
8823116/2 8826050.
E-mail address: fqadri@icddrb.org
Abstract
Background: The objective of this study was to
examine the clinical and immunological
features of cholera in pregnancy.
Methods: Women of reproductive age presenting to the
icddr,b Dhaka hospital with cholera, and
enrolled as part of a larger cohort study, were
tested for pregnancy on admission. We compared
initial clinical features and immune responses of
pregnant patients with non-pregnant female
patients at days 2, 7 and 21 after infection.
Results: Among reproductive age women enrolled
between January 2001 and May 2006, 9.7%
(14/144) were pregnant. The duration of diarrhea
prior to admission tended to be higher in
pregnant compared to non-pregnant patients (p=0.08),
but other clinical characteristics did not
differ. Antibody responses to cholera toxin B
subunit (CtxB), toxin-coregulated pilus A (TcpA),
Vibrio cholerae lipopolysaccharide (LPS), and serum
vibriocidal antibody responses, were
comparable between pregnant and non-pregnant
patients. There were no deaths among the
pregnant cases or non-pregnant controls, and no
adverse fetal outcomes, including stillbirths,
during 21 days of follow up of pregnant cases.
Conclusions: To our knowledge, this is the first
report of immune responses in pregnant women
with cholera. We found that pregnant woman early in
pregnancy has comparable clinical illness
and subsequent immune responses compared to
non-pregnant women. These findings suggest
that the evaluation of safety and immunogenicity of
oral cholera vaccines in pregnancy should be
an area of future investigations.
Key words: Cholera, immune response, pregnancy
Page 4 of 19
Accepted Manuscript
1. Introduction
Cholera is a life threatening diarrheal disease
caused predominantly by infection with Vibrio
cholerae O1. Though cholera is rare in developed
countries, it is prevalent in many areas of
South and Southeast Asia and in Africa and may also
cause major outbreaks worldwide [1].
Bangladesh is a country in South Asia where cholera
is endemic and is consistently present
throughout the year in high risk areas [2]. Cholera
toxin (CT), the primary toxin produced by V.
cholerae O1 and O139, causes the hypersecretion of
electrolytes and water, sometimes with fatal
results. The lipopolysaccharide of V. cholerae is an
important determinant of protection, and is
the primary antigen found in the most recent
formulations of the oral cholera vaccine (OCV).
Pregnancy is an immuno-altered state where both
humoral and cellular immunity are affected [3,
4]. Several pregnancy outcomes, including
preeclampsia, poor fetal growth, and preterm birth,
have been linked to abnormalities in immune
responses during pregnancy [5-7]. Pregnancy has
also been associated with decreased inflammatory
responses and increased anti-inflammatory
responses to immune challenges in humans as well as
in animal models [8, 9]. In some cases,
pregnant women are more susceptible to certain
infections, and when infected, may experience a
higher severity of illness. For example, pregnant
women infected with influenza virus are at
increased risk for serious complications when
compared to other groups [10], though a recent
study on influenza virus vaccine during pregnancy
showed that pregnancy did not significantly
alter antibody responses [11].
Women living in areas endemic for cholera are at
risk of acquiring the disease during pregnancy,
and studies from South Asia, Africa, and Haiti have
demonstrated that cholera during pregnancy
may increase the risk of poor outcomes [12].
However, there is a lack of data on the
immunological responses to cholera during pregnancy
to determine if vaccination might play a
role in prevention. Thus, the objective of this
study was to examine the clinical characteristics
and immunological responses of pregnant women
following severe cholera.
2. Materials and Methods
2.1 Study population and patient enrolment
The Cholera Immune Response Study (CIRS) was a
prospective, observational study, undertaken
as a collaboration between the International Centre
for Diarrhoeal Disease Research, Bangladesh
(icddr,b) and Massachusetts General Hospital in
Boston. The icddr,b in Dhaka, Bangladesh cares
for approximately 120,000 patients with diarrheal
diseases each year. Patients presenting to the
icddr,b Dhaka hospital with acute watery diarrhea
(study day 1) were eligible for inclusion in this
study if their stool cultures were subsequently
positive for V. cholerae, and if they were without
significant co-morbid conditions; patients were
enrolled prospectively in the study between 2001
and 2006 [13, 14]. Stool cultures for V. cholerae
were done on taurocholate-tellurite-gelatin agar
(TTGA). After overnight incubation of plates,
serological confirmation of suspected V. cholerae
colonies was carried out by slide agglutination
[15]. Patients were enrolled on day 2 of admission
(study day 2) if a stool culture was positive for V.
cholerae O1 or O139. Information regarding
clinical features, demographics, and history of
diarrhea were collected from patients at
enrollment. Samples of venous blood were collected,
for determining antibody titers, from
patients on study day 2 and again at follow-up
visits on study days 7 and 21. Informed written
consent for participation in this research was
obtained from participants or their guardians. This
study was reviewed and approved by the Ethical and
Research Review Committees of the icddr,b
and the Institutional Review Board of the
Massachusetts General Hospital.
2.2 Pregnant women and case control comparison
All women of reproductive age (15-49) enrolled in
the CIRS study were screened for pregnancy
by urine strip test (hCG One Step Pregnancy Test
Strip, TUV product service, USA) on
enrollment. A total of 14 women had a positive
pregnancy test. We also selected all nonpregnant
cases as controls from the same age cohort.
2.3 Treatment of patients
Patients enrolled for the study received the normal
standard of care provided at the icddr,b for
cholera. Dehydration was corrected either by
infusing intravenous cholera saline or by oral
rehydration solution depending on the severity of
the dehydration and clinical condition of the
patient. A short course of oral antibiotics was
given. Non pregnant adult females with stool
culture positive for V. cholerae received 300 mg of
doxycycline in a single dose, whereas
pregnant women with cholera received erythromycin
(500 mg every six hours) for three days.
2.4 Immunological assessment
We measured vibriocidal antibodies in patient plasma
using V. cholerae O1 El Tor Ogawa (strain
X25049) or Inaba (strain 19479) or V. cholerae O139
(strain 4260B) as target bacteria, and
adding guinea pig complement [16]. Antibody
responses to recombinant cholera toxin B subunit
(CtxB), toxin-coregulated pilus A subunit (TcpA),
and lipopolysaccharide (LPS) were
determined using a kinetic enzyme-linked
immunosorbent assay (ELISA), as previously
described [17]. In all cases, the vibriocidal and
LPS responses were measured to the same
serotype, Ogawa or Inaba of V. cholerae O1 and V.
cholerae O139 as was present in the patient.
2.5 Data analyses
Data analyses were performed using SPSS for Windows
(version 12; SPSS Inc., Chicago, IL,
USA) and Epi Info (version 6.0; USD, Stone Mountain,
GA, USA). For non-normally distributed
data, comparisons were carried out as median
(25th–75th percentile) using the Mann–Whitney
U-test. The significance of differences in
proportions was evaluated by the Chi-square test, and
Fisher’s exact test was applied when appropriate. A
p-value of <0.05 was considered statistically
significant.
3. Results
A total of 399 patients with cholera were enrolled
in the study between January 2001 and May
2006 and the data obtained prospectively were
analyzed in a retrospective fashion. Overall, 144
cholera patients were reproductive age (15-49 years)
women and of those, 9.7% (14/144) had a
positive pregnancy test. Average duration of
pregnancy was 14 weeks at enrollment (minimum 6
weeks, maximum 24 weeks, mean ±SD = 14±5.6 weeks)
(data not shown). The clinical and
microbiological features of the pregnant and
non-pregnant cholera cases are presented in Table 1.
The duration of diarrhea prior to admission trended
toward higher (p=0.08) in the pregnant
cohort compared to the non-pregnant control cohort
of patients with cholera. However, other
clinical parameters, including severity of dehydration
and volume of intravenous fluids required,
did not differ between the pregnant and non-pregnant
cholera cases (Table 1). There were no
deaths among the pregnant cases or non-pregnant
controls, and no adverse fetal outcomes
including spontaneous abortions in the 21 days
following cholera in the pregnant women.
We assessed the association between the baseline
(Day 2) and convalescent stage (Day 7 and 21)
responses in a number of immunologic markers and
pregnancy status of cholera patients. Serum
vibriocidal titers (Table 2), as well as antibody
responses to LPS, CtxB, and TcpA (Table 3, 4,
5), showed no statistically significant differences
between pregnant and non-pregnant patients
overall. However, when we compared responses
separately for V. cholerae O1 and O139
infected patients, serum vibriocidal responses and
as well as antibody response to LPS and CtxB
were higher in non-pregnant women compared to
pregnant women infected with V. cholerae
O139 (Tables 2, 3, 4).
4. Discussion
This is the first report to our knowledge of immune
responses following cholera in pregnant
women. We found that overall, most of the clinical
and immunological characteristics were
comparable between pregnant and non-pregnant women
presenting to the icddr,b hospital with
severe cholera. When analyzed separately for
patients infected with V .cholerae O1 versus O139,
the vibriocidal antibody responses following O1
infection were more robust in general than those
seen following O139 infection, as we have seen
earlier [16]. Serum vibriocidal responses as well
as antibody responses to LPS, CtxB and TcpA were
similar between pregnant and non-pregnant
women infected with V. cholerae O1. Pregnant women
infected with V. cholerae O139 had
lower serum vibriocidal responses and antibody
responses to LPS and CtxB compared to nonpregnant
women infected with this serogroup. This study also
found no deaths among the
pregnant cases or non-pregnant controls, and no
adverse fetal outcomes during 21 days of follow
up of the pregnant cases. Of note, our follow up
period was limited to 21 days after infection,
and the infected pregnant women were in the first or
second trimester.
In a study from Haiti, a previously non-endemic
area, analysis of outcome data from a large
cohort of pregnant women with cholera revealed that
the main risk factor for fetal death was
severity of dehydration [12]. Although our study did
not follow the outcome of pregnancy for
more than the 21 day follow up period after the
episode of cholera, we did not find any
difference in the severity of dehydration between
pregnant and non-pregnant women presenting
in the first or second trimester with severe
cholera. At icddr,b severe dehydration is immediately
corrected with cholera saline following presentation
to the facility. The management of
individuals with cholera involves fluid
resuscitation based on the level of dehydration and then
after adequate hydration, maintenance of ongoing
fluid losses [18]. Cholera in the third trimester
has previously been significantly associated with an
increased severity of diarrhoeal disease, as
indicated by severe dehydration on admission to
hospital, as compared with non-pregnant controls [19].
Several studies also suggest an association between
fetal loss and the degree of dehydration and
hypovolemia [19-21]. Independent of the dehydration
status, severe vomiting was also found to be
another risk factor for fetal death [12]. Changes in
electrolytes in the amniotic fluid of pregnant women
suffering from cholera have been described in the
literature [22], but it remains unclear how these affect
the fetus. In our study, it is notable that vomiting
was not significantly different between pregnant patients
in the first and second trimester and non-pregnant
cholera patients.
The serum vibriocidal antibody assay has been used
to measure the antibacterial antibody response in
cholera patients and elevated vibriocidal antibody
levels have been shown to correlate with protection
against cholera [16, 23, 24]. This has led to the
use of serum vibriocidal antibody responses as a
surrogate marker for cholera vaccine efficacy. In
our study, serum vibriocidal responses did not differ
between pregnant and non-pregnant cholera patients
infected with V. cholerae O1, the major currently
circulating serogroup.
LPS is an important antigen for enteric pathogens
and responses to LPS appear to be involved in
protection against cholera [25]. For example, V.
cholerae O1 LPS has been shown to induce
protective immune responses in humans and animals
[26, 27] and thus its use as a protective
immunogen for cholera vaccine development has been
widely accepted [28, 29]. We did not find
any statistically significant differences in LPS
antibody responses between pregnant and nonpregnant
cholera patients infected with V. cholerae O1. In cholera-endemic
countries like
Bangladesh, vaccinating the entire population may
not be possible. However vaccination can be
targeted in high-risk areas and to select high-risk
populations that are especially vulnerable to
severe disease; these targeted groups might include
pregnant women if the vaccine is found to be
safe in pregnancy. One recent study in Zanzibar
found no statistically significant evidence of a
harmful effect of gestational exposure to oral
cholera vaccine [30]. Thus the evaluation of oral
cholera vaccines and subsequent use in pregnant
women should be considered an important
priority.
The main limitation of this study is the fact that
the cohort consisted of only patients with severe
cholera requiring hospitalization. Since many cases
of infection with V. cholerae O1 do not
result in severe infection, the association between
pregnancy and the full spectrum of disease
severity cannot be gauged in this study. Another
limitation of this study is that we had a small
sample size (14 pregnant women with cholera) and
only followed pregnancy outcomes until 21
days after infection and we did not gather data on
later fetal outcomes. Also, we did not assess
mucosal immune responses using the
antibody-secreting cell or antibody-in-lymphocyte
supernatant assay for all the patients in this
study. As most of the pregnant women were in the
initial stage of gestation (average duration of
pregnancy was 14 weeks), this may explain why
the women had similar clinical severity unlike other
studies later in pregnancy. The small sample
size of pregnant women assessed for clinical
severity, as well as the inclusion of only women
with severe cholera, suggest that we did not have
sufficient power for a full accounting of the
severity of disease in pregnancy. Despite these
limitations, to our knowledge, our study
represents a unique analysis of immune responses to
cholera during pregnancy.
In conclusion, we have shown that pregnant women
with severe cholera due to V. cholerae O1
respond immunologically in a similar manner to
non-pregnant women despite the immune
alterations associated with pregnancy. Our data
underscore the fact that pregnant women with
cholera are able to mount normal vibriocidal and
other anti-V. cholerae immune responses.
These findings suggest that the evaluation of safety
and immunogenicity of oral cholera vaccines
in pregnancy should be an area of future
investigations so that the use of oral killed cholera
vaccine in pregnant women at risk of cholera can be
considered.
Acknowledgements
This study was supported by the following grants:
U01 AI058935; AI106878 and K08
AI100923. Additionally the study was also supported
by core grants to the icddr,b. The icddr,b is
thankful to the Governments of Australia,
Bangladesh, Canada, Sweden and the UK for
providing core/unrestricted support. We wish to
thank the study participants and the dedicated
clinical, field and laboratory and data management
staff of the Cholera Immune Response study.
Conflicts of Interest
There are no conflicts of interest by authors.
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Table 1
Clinical and microbiological features of pregnant
and all non-pregnant study participants
Characteristics Pregnant (n=14) Non-pregnant
(n=130)
p-value
Demographics
Median age (yr), (25th, 75th percentile) 24.5 (21 -
29) 27 (21 - 36) 0.14
Blood group, n (%)
O 4 (28.6) 58 (44.6)
A 2 (14.3) 36 (27.7)
B 6 (42.9) 31 (23.9)
AB 2 (14.3) 5 (3.9) 0.09
Clinical
Dehydration
Some 1 (7.1) 9 (6.9)
Severe 13 (92.9) 121 (93.18) 1.00
No. of stools (> 20 in last 24hrs) 10 (71.4) 111
(85.48) 0.24
Fever in the last week 2 (14.3) 27 (20.8) 0.74
Vomiting in the last 24hrs
No or <10 times 5 (35.7) 65 (50.0)
≥ 10 times 9 (64.3) 65 (50.0) 0.40
Abdominal pain at presentation 11 (78.6) 93 (71.5)
0.76
Helminth present 2 (14.3) 16 (12.3) 0.69
Received IV fluid 13 (92.9) 126 (96.9) 0.41
Duration of diarrhea, hr
Median (IQR) 100 (9 - 105) 12 (7 - 23) 0.08
Duration of stay, hr
Median (IQR) 102 (41 - 104) 103 (100 - 105) 0.25
Microbiological, n (%)
Dark field positive stool
V. cholerae O1, Ogawa 3 (21.4) 41 (31.5) 0.55
V. cholerae O1, Inaba 7 (50.0) 66 (50.8) 1.00
V. cholerae O139 4 (28.6) 23 (17.7) 0.30
Table 2
Vibriocidal antibody responses of study participants
by pregnancy status
Infecting strain Antibody Pregnant (n=14)
Non-pregnant (n=130)
n Median (IQR) n Median (IQR)
p-value
Vibriocidal
(*Study Days)
Day 2 14 80 (10 - 640) 128 80 (20 - 160) 0.84
Day 7 14 2560 (1280 - 8960) 122 5120 (2560 - 10240)
0.32
Overall
Day 21 11 2560 (640 - 5120) 120 2560 (1280 - 5120)
0.66
Day 2 10 480 (50 - 640) 105 80 (40 - 320) 0.19
Day 7 10 3840 (2560,17920) 99 5120 (2560 - 10240)
0.97
V.cholerae O1
Day 21 9 5120 (1280,5120) 97 5120 (1280 - 5120) 0.95
Day 2 4 8 (5 - ,28) 23 20 (10 - 80) 0.27
Day 7 4 640 (520 - 800) 23 1280 (640 - 2560) 0.10
V. cholerae O139
Day 21 2 163 (84 - 241) 23 640 (640 - 1280) 0.05
*Patients presenting to the icddr,b Dhaka hospital
with acute watery diarrhea (study day 1); Antibody
titers, from patients at baseline on study day 2 and
again at follow-up visits on study days 7 and 21.
Page 17 of 19
Accepted Manuscript
Table 3
Responses to LPS of study participants by pregnancy
status
Infecting strain Antibody Pregnant (n=14)
Non-pregnant (n=130)
(*Study
Days)
n Median (IQR) n Median (IQR)
p-value
LPS IgA
Day 2 14 22 (18 - 31) 130 22 (12 - 39) 0.95
Day 7 14 103 (32 - 250) 124 151 (73 - 268) 0.26
Day 21 11 81(30 - 177) 120 97 (49 - 184) 0.49
LPS IgG
Day 2 14 72 (47 - 122) 130 79 (55 - 106) 0.87
Day 7 14 180 (98 - 248) 124 227 (164 - 292) 0.12
Overall
Day 21 11 258 (106 - 283) 120 238 (150 - 313) 0.30
LPS IgA
Day 2 10 24 (19 - 31) 107 21 (11 - 37) 0.49
Day 7 10 169 (87 - 308) 101 162 (74 - 293) 0.97
Day 21 9 106 (30 - 184) 97 89 (43 - 200) 0.80
LPS IgG
Day 2 10 99 (60 - 138) 107 75 (55 - 103) 0.30
Day 7 10 224 (158 - 259) 101 226 (163 - 297) 0.73
V.cholerae O1
Day 21 9 268 (123 - 298) 97 230 (146 - 318) 0.91
LPS IgA
Day 2 4 21 (14 - 26) 23 30 (14 - 42.67) 0.25
Day 7 4 38 (21 - 54.17) 23 102 (64 - 170) 0.02
Day 21 2 47 (38 - 55.33) 23 117 (68 - 158) 0.09
LPS IgG
Day 2 4 53 (37 - 64) 23 90 (72 - 111) 0.02
Day 7 4 107 (81 - 130) 23 228 (195 - 277) 0.01
V. cholerae O139
Day 21 2 83 (75 - 91) 23 246 (219 - 300) 0.03
*Patients presenting to the icddr,b Dhaka hospital
with acute watery diarrhea (study day 1); Antibody
titers, from patients at baseline on study day 2 and
again at follow-up visits on study days 7 and 21.
Table 4
Responses to CtxB of study participants by pregnancy
status
Infecting strain Antibody Pregnant (n=14)
Non-pregnant (n=130)
(*Study
Days)
n Median (IQR) n Median (IQR)
p-value
CtxB IgA
Day 2 14 19 (16 - 38) 130 22 (12 - 44) 0.75
Day 7 14 92 (58 - 160) 124 123 (65 - 204) 0.49
Day 21 11 56 (48 - 115) 120 71 (41 - 125) 0.89
CtxB IgG
Day 2 14 109 (75 - 131) 130 98 (61 - 157) 0.87
Day 7 14 288 (213 - 352) 124 260 (194 - 425) 0.98
Overall
Day 21 11 369 (252 - 401) 120 285 (213 - 399) 0.40
CtxB IgA
Day 2 10 20 (16 - 60) 107 22 (12 - 41) 0.75
Day 7 10 92 (64 - 156) 101 111 (57 - 175) 0.96
Day 21 9 68 (48 - 135) 97 67 (36 - 100) 0.44
CtxB IgG
Day 2 10 117 (85 - 131) 107 99 (63 - 160) 0.70
Day 7 10 288 (266 - 347) 101 260 (191 - 411) 0.52
V.cholerae O1
Day 21 9 378 (281 - 411) 97 286 (202 - 410) 0.13
CtxB IgA
Day 2 4 19 (16 - 20) 23 25 (15 - 49) 0.19
Day 7 4 97 (52 - 151) 23 191 (129 - 304) 0.08
Day 21 2 50 (49 - 51) 23 107 (74 - 176) 0.04
CtxB IgG
Day 2 4 92 (63 - 119) 23 75 (53 - 132) 1.00
Day 7 4 231 (124 - 327) 23 260 (219 - 430) 0.25
V. cholerae O139
Day 21 2 180 (151 - 209) 23 282 (234 - 385) 0.11
*Patients presenting to the icddr,b Dhaka hospital
with acute watery diarrhea (study day 1); Antibody
titers, from patients at baseline on study day 2 and
again at follow-up visits on study days 7 and 21.
Table 5
Responses to TcpA of study participants by pregnancy
status
Infecting strain Antibody Pregnant (n=14)
Non-pregnant (n=130)
(Study
Days)
n Median (IQR) n Median (IQR)
p-value
TcpA IgA
Day 2 9 5 (2 - 5) 79 6 (3 - 11) 0.08
Day 7 9 13 (7 - 33) 77 22 (7 - 46) 0.91
Day 21 9 12 (9 - 37) 76 11 (6 - 26) 0.26
TcpA IgG
Day 2 7 30 (20 - 40) 58 40 (24 - 65) 0.21
Day 7 7 66 (65 - 142) 56 64 (35 - 128) 0.41
Overall
Day 21 7 90 (58 - 130) 55 77 (44 - 120) 0.47
TcpA IgA
Day 2 7 3 (2 - 5) 68 6 (3 - 11) 0.07
Day 7 7 13 (6 - 23) 66 23 (6 - 46) 0.62
Day 21 7 12 (10 - 35) 65 13 (6 - 27) 0.44
TcpA IgG
Day 2 6 26 (20 - 35) 57 42 (24 - 65) 0.15
Day 7 6 66 (64 - 110) 55 56 (35 - 123) 0.65
V.cholerae O1
Day 21 6 100 (51 - 131) 54 76 (40 - 122) 0.46
TcpA IgA
Day 2 2 5 (4.6 - 4.9) 11 5 (4 - 5) 1.00
Day 7 2 104 (57 - 152) 11 14 (7 - 36) 0.43
Day 21 2 47 (28 - 66) 11 10 (8 - 11) 0.43
Tcp IgG
Day 2 1 43 (43 - 43) 1 26 (26 - 26) 0.32
Day 7 1 160 (160 - 160) 1 127 (127 - 127) 0.32
V. cholerae O139
Day 21 1 90 (90 - 90) 1 101 (101 - 101) 0.32
*Patients presenting to the icddr,b Dhaka hospital
with acute watery diarrhea (study day 1); Antibody
titers, from patients at baseline on study day 2 and
again at follow-up visits on study days 7 and 21.
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