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Dispatch
Fluid Intake and Decreased
Risk for Hospitalization for Dengue Fever, Nicaragua
Eva Harris,* Leonel Pérez,† Christina R. Phares,* Maria de los Angeles
Pérez,‡ Wendy Idiaquez,‡ Julio Rocha,§ Ricardo Cuadra,§ Emelina Hernandez,¶
Luisa Amanda Campos,† Alcides Gonzalez,† Juan Jose Amador,† and Angel
Balmaseda†
*University of California, Berkeley, California, USA; †Ministerio de Salud,
Managua, Nicaragua; ‡Hospital Infantil Manuel de Jesús Rivera, Managua,
Nicaragua; §Hospital Escuela Oscar Danilo Rosales Argüello, Leon, Nicaragua;
and ¶Centro de Salud Francisco Buitrago, Managua, Nicaragua
Suggested citation for this article: Harris E, Pérez
L, Phares DR, de los Angeles Pérez M, Idiaquez W, Rocha J, et
al. Fluid intake and decreased risk for hospitalization for dengue fever,
Nicaragua. Emerg Infect Dis [serial online] 2003 Aug [date cited].
Available from: URL: http://www.cdc.gov/ncidod/EID/vol9no8/02-0456.htm
In a hospital and
health center–based study in Nicaragua, fluid intake during the 24 hours
before being seen by a clinician was statistically associated with decreased
risk for hospitalization of dengue fever patients. Similar results were
obtained for children <15 years of age and older adolescents and
adults in independent analyses.
Dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome
(DHF/DSS) are major public health problems worldwide (1).
In addition to causing considerable illness and death, dengue epidemics
also have a major economic impact, attributable primarily to the cost
of medical care, plus vector control programs and lost productivity (2,3).
DF and DHF/DSS are indistinguishable in the initial febrile phase, and
few reliable clinical prognostic indicators of DHF/DSS exist (4).
Near the time of defervescence, the plasma leakage syndrome of DHF/DSS
can develop suddenly and be fatal if not managed properly. As a result,
in areas relatively new to dengue, such as Latin America where DF and
DHF/DSS have been spreading over the last 2 decades, high hospitalization
rates for DF can occur because of the fear of discharging a patient whose
case may progress to DHF/DSS. As DHF/DSS becomes hyperendemic, as in Southeast
Asia, and extensive experience is garnered in case management, most hospitalizations
for dengue are due to frank DHF/DSS. We conducted a study to assess the
extent of hospitalization attributable to dengue in Nicaragua and to examine
the role of factors such as prior fluid intake on the risk for hospitalization.
The Study
Participating hospitals and health centers in urban centers of the Pacific
region of Nicaragua included the Hospital Escuela Oscar Danilo Rosales
Argüello in León, the pediatric reference Hospital Infantil Manuel de
Jesus Rivera in Managua, and four health centers in Managua, which serve
a combined population of 1.95 million people. A cross-sectional study
of 2,820 suspected dengue cases was conducted from January 1 to December
31, 1999. Enrollment criteria consisted of acute febrile illness accompanied
by two or more of the following symptoms of DF: fever, severe headache,
retroorbital pain, myalgias, arthralgias, and rash (4,5).
A standardized questionnaire was used to collect demographic and clinical
information, including ingestion of fluids in the 24 hours before first
being seen by a clinician, as reported by the patient or parent. Of the
1,312 patients who tested positive for DENV infection, the mean age was
15.3 years (range 0–85), and 557 (42%) were male (Table
1). Venous blood was drawn at the first visit, and convalescent-phase
serum specimens were obtained when possible (19% of patients). Clinical
evolution of the illness among hospitalized patients was documented by
chart review with standardized data-entry forms. This study was approved
by the Institutional Review Boards of both University of California, Berkeley
(#99-4-38) and the Centro Nacional de Diagnóstico y Referencia of the
Nicaraguan Ministry of Health (#99-04).
Dengue virus (DENV) infection was identified in 1,312 patients by serologic
methods (immunoglobulin M-capture enzyme-linked immunosorbent assay [ELISA]
or inhibition ELISA for total anti-DENV antibodies), virologic means (virus
isolation, reverse transcriptase-polymerase chain reaction), or both (5).
DENV2, DENV4, and DENV3 accounted for 79%, 17%, and 5% of the typed viruses,
respectively. Dengue fever was divided into classic DF and DF with hemorrhagic
manifestations (DFHem); severe dengue was defined as DHF (World Health
Organization classification DHF grades I and II), DSS (World Health Organization
DHF grades III and IV) (1), or an additional classification
designated “dengue with signs associated with shock” (DSAS). DSAS was
designated when either hypotension for age or narrow pulse pressure plus
clinical signs of shock were present and serial hematocrit and platelet
counts failed to document thrombocytopenia and hemoconcentration, potentially
attributable to fluid replacement therapy (5). The relationship
between hospitalization and fluid intake was assessed by unconditional
logistic regression. Because virtually every patient with severe dengue
was hospitalized, such risk factor analysis was not suitable for these
patients as a separate group. Thus, the analysis was restricted to DF
and DFHem patients. Univariate and multivariate analyses were performed
separately on children (<15 years of age) and older adolescents and
adults (>15 years of age). Covariates found to be significant
in univariate analyses were included in the initial multivariate models
(Table 2).
Although a much higher proportion of severe dengue patients were hospitalized
compared with DF and DFHem patients, larger absolute numbers of hospitalizations
were due to classic DF and DFHem because many more cases of DF/DFHem than
of severe dengue occur (Table 1). Thus, of all the
laboratory-confirmed DENV-positive hospitalized patients, classic DF (23.5%)
and DFHem (50.0%) cases comprised three times as many as DHF, DSS, and
DSAS combined (23.6%). These profiles have been maintained from year to
year, with 28% and 20% of hospitalized cases due to classic DF and 51%
and 58% due to DFHem in 1998 and 2000, respectively (5).
Furthermore, the mean duration of hospitalization was similar for patients
with DF and those with severe dengue (Table 1).
Conclusions
Among children with DF or DFHem, ingestion of fluid in the 24 hours before
being seen by a clinician was found to be protective against hospitalization
after adjusting for distance from health facility, date of symptom onset,
and thrombocytopenia (odds ratio [OR]=0.74 per each additional glass consumed,
95% confidence intervals [CI] 0.66 to 0.83, p<0.01) (Table
2). Similar results were obtained for older adolescents and adults
after adjusting for date of symptom onset and thrombocytopenia, with an
OR of 0.71 (95% CI 0.59 to 0.85, p<0.01). In analyses with a statistical
model that did not assume a linear relationship between number of glasses
ingested and hospitalization, additional benefit was noted for each glass
up to five, after which the incremental benefit remained constant. Thus,
in a model that compared the fluid intake of five glasses or less than
five glasses with ingestion of more than five glasses, the adjusted OR
for hospitalization was 0.19 (95% CI 0.09 to 0.39, p<0.01) among DF
and DFHem cases in children and 0.20 (95% CI 0.07 to 0.57, p<0.01)
in those >15 years of age (Table 2). We
also performed the analysis with all disease states, including severe
dengue cases, and the results were virtually identical to those obtained
with only DF/DFHem cases (data not shown).
The most common liquid ingested was water (70%), followed by fruit juice
(42%), lemonade (27%), milk (25%), coffee (14%), oral dehydration serum
(6%), and tea (2%). The mean number of glasses ingested by nonhospitalized
DF/DFHem case-patients was 5.2, whereas the mean number glasses ingested
by hospitalized DF/DFHem patients was 2.8, similar to the mean of 2.9
glasses ingested by hospitalized severe patients (DHF/DSS/DSAS). These
findings suggest that maintaining hydration may lead to reduced hospitalizations
of patients with DF/DFHem. Other independent risk factors for hospitalization
included in the final multivariate model were increasing distance from
the healthcare facility, later date of symptom onset, and the presence
of thrombocytopenia. The risk conferred by later date of symptom onset
reflects increased awareness of dengue by medical staff as the annual
epidemic intensified. Because thrombocytopenia is an indication for hospitalization
(especially for pediatric dengue patients), its emergence as a risk factor
is not surprising.
Because inpatient medical care of DF and DFHem patients can contribute
significantly to the economic impact of dengue, we sought to define outpatient
measures that could decrease DF hospitalization rates. Dengue patients
are likely to be susceptible to dehydration because of high fever and
concomitant anorexia. While oral rehydration therapy is listed as standard
outpatient management for DHF (1), little discussion
exists on the use of such therapy for DF and DFHem cases (4),
and no published studies have examined the effect of fluid intake at home.
Our results show that this simple measure may have a significant protective
effect against hospitalization and potentially on the severity of DF/DFHem,
although causality cannot be confirmed because of the observational nature
of this study. To definitively demonstrate this effect, this question
must be investigated by prospective intervention studies. However, our
data do suggest that promoting a high fluid intake at home could help
reduce the need for hospitalization and thus attenuate economic impact
of dengue in countries experiencing epidemics of dengue fever.
Acknowledgments
We are grateful
to the hospital and health center staff, personnel in the Centro Nacional
de Diagnóstico y Referencia virology laboratory, and the persons who
participated in the study. We thank Art Reingold, Albert Ko, Scott Halstead,
Michael Diamond, and Laurel Imhoff for helpful discussions or editorial
comments.
This work was supported
by grant #TW-00905 from the Fogarty International Center, National Institutes
of Health.
Dr. Harris is an
assistant professor in the Division of Infectious Diseases in the School
of Public Health at the University of California, Berkeley, where her
research program focuses on the pathogenesis and epidemiology of dengue
virus. Over the past 8 years, she has collaborated with scientists at
the Nicaraguan Ministry of Health to strengthen dengue surveillance
and investigate the epidemiology of dengue in Nicaragua.
References
- World Health Organization. Dengue haemorrhagic fever:
diagnosis, treatment, prevention, and control. 2nd ed. Geneva: The Organization;
1997.
- Von Allmen SD, Lopez-Correa RH, Woodall JP, Morens DM, Chiribiga J,
Casta-Velez A. Epidemic
dengue fever in Puerto Rico, 1977: a cost analysis. Am J Trop Med
Hyg 1979;28:1040–4.
- Ferrando JE. Estimate of the costs of the dengue epidemic in 1994
in Nicaragua. Pan American Health Organization Consultancy Report. OPS/HCP/HCT/95.64.
Washington, DC: Pan American Health Organization;1995.
- Pan American Health Organization. Dengue and dengue hemorrhagic fever
in the Americas: guidelines for prevention and control. Scientific pub.
no. 548. 1994. Washington, DC: The Organization; 1994.
- Harris E, Videa E, Perez L, Sandoval E, Tellez Y, Perez ML, et al.
Clinical,
epidemiologic, and virologic features of dengue in the 1998 epidemic
in Nicaragua. Am J Trop Med Hyg 2000;63:5–11.
| Table
1. Characteristics of all hospitalized and unhospitalized dengue
patientsa |
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|
Data
|
Hospitalized cases
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Unhospitalized cases
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Total
|
|
|
|
|
n
|
Mean (sd) or % of group
|
n
|
Mean (sd) or % of group
|
n
|
Mean (sd) or % of group
|
|
|
Demographic data
|
|
|
|
|
|
|
Age (y)
|
478
|
9.4 (8.9)
|
834
|
18.7 (15.5)
|
1,312
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15.3 (14.2)
|
Male
|
229
|
47.8%
|
328
|
39.2%
|
557
|
42.3%
|
|
Distance (km) to health facility
|
464
|
10.0 (25.0)
|
831
|
2.7 (6.1)
|
1,295
|
5.3 (16.1)
|
|
Disease classificationa
|
|
|
|
|
|
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Classic DF
|
113
|
23.5%
|
706
|
84.4%
|
819
|
62.1%
|
DFHem
|
240
|
50.0%
|
129
|
15.4%
|
369
|
28.0%
|
DHF
|
67
|
14.0%
|
0
|
0%
|
67
|
5.1%
|
DSS
|
16
|
3.3%
|
1
|
0.1%
|
17
|
1.3%
|
DSAS
|
30
|
6.3%
|
0
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0%
|
30
|
2.3%
|
No classification
|
14
|
2.9%
|
1
|
0.1%
|
15
|
1.1%
|
|
Duration of hospitalization (days)b
|
|
|
|
|
|
|
Classic DF
|
52
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5.7 (1.7)
|
|
|
|
|
DFHem
|
95
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5.1 (1.7)
|
|
|
|
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DHF
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56
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6.1c (1.5)
|
|
|
|
|
DSS
|
15
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6.9c,d (1.9)
|
|
|
|
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DSAS
|
28
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6.1c (1.8)
|
|
|
|
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No classification
|
11
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6.2 (1.9)
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|
|
|
|
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Clinical data at presentation
|
|
|
|
|
|
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No. of glasses of fluid ingested during previous
24 he
|
331
|
2.9 (2.3)
|
757
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5.6 (3.9)
|
1,088
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4.8 (3.7)
|
Thrombocytopenia
|
289
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60.2%
|
58
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6.9%
|
347
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26.4%
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Anorexia
|
239
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50.9%
|
422
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53.3 %
|
661
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52.4%
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Stomach pain
|
271
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58.4%
|
404
|
51.5%
|
675
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54.4%
|
Days since onset of symptoms
|
476
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5.5 (5.6)
|
826
|
5.2 (5.7)
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1,302
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5.3 (5.7)
|
|
|
aDF, dengue fever; DFHem, DF with hemorrhagic
manifestations; DHF, dengue hemorrhagic fever; DSS, dengue shock
syndrome; DSAS, dengue with signs associated with shock.
|
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bInformation on the duration of hospitalization
was available from 52 (46%) of hospitalized classic DF patients;
95 (40%) of hospitalized DFHem patients; 56 (84%) of hospitalized
DHF patients; 15 (94%) of hospitalized DSS patients; and 28 (93%)
of hospitalized DSAS patients. Outliers (>12 days) were
removed before analysis.
|
|
cThe mean duration of hospitalization
was significantly longer for DHF cases, DSS cases, and DSAS cases
as compared with duration for DFHem cases (p<0.05 for each, Student
t test).
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dThe mean duration of hospitalization
was significantly longer for DSS cases compared with duration for
classic DF cases (p<0.05, Student t test).
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eThe average glass contains approximately
8 oz.
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Table 2. Crude and adjusted
odds ratios and 95% confidence intervals for factors potentially
associated with hospitalization for classic dengue fever or dengue
fever with hemorrhagic manifestations
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Characteristic
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Children (<15 years of age)a
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Older adolescents and adults
(>15 years of age)a
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No. of patientsb
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OR (95% CI)c
Crude
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OR (95% CI)c
Adjustedd
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No. of patientsb
|
OR (95% CI)c
Crude
|
OR (95% CI)c
Adjustedf
|
|
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Fluid intake during 24-h period before presentation
|
587
|
|
|
405
|
|
|
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For each additional glass
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0.68 (0.62 to 0.75)
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0.74 (0.66 to 0.83)
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0.67 (0.5 to 0.79)
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0.71 (0.59 to 0.85)
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>5 glasses
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0.14 (0.08 to 0.25)
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0.19 (0.09 to 0.39)e
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0.16 (0.06 to 0.43)
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0.20 (0.07 to 0.57)g
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Age
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719
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—h
|
464
|
|
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For each additional year
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0.93 (0.8 to 0.97)
|
|
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0.98 (0.96 to 1.00)
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Sex
|
718
|
|
|
464
|
|
|
|
Male
|
395
|
1.43 (1.06 to 1.94)
|
|
291
|
1.27 (0.74 to 2.17)
|
|
|
Female
|
323
|
|
|
173
|
|
|
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Distance from healthcare facility
|
701
|
|
|
460
|
|
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For each additional 5 km
|
|
2.13 (1.68 to 2.69)
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1.46 (1.12 to 1.91)
|
|
1.16 (0.92 to 1.46)
|
—
|
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Date of onset of symptoms
|
709
|
|
|
455
|
|
|
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For each additional month
|
|
1.26 (1.16 to 1.37)
|
1.51 (1.26 to 1.81)
|
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1.87 (1.53 to 2.29)
|
2.08 (1.53 to 2.83)
|
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Days between onset of symptoms and being seen
at facility
|
713
|
|
|
457
|
|
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For each additional day
|
|
1.04 (1.0 to 1.07)
|
—
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0.98 (0.93 to 1.03)
|
—
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Thrombocytopenia
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499
|
|
|
227
|
|
|
|
Yes
|
189
|
6.5 (4.25 to 9.96)
|
6.16 (3.57 to 10.64)
|
33
|
3.31 (1.53 to 7.15)
|
3.62 (1.24 to 10.52)
|
|
No
|
310
|
|
|
194
|
|
|
|
Stomach pain
|
681
|
|
|
439
|
|
|
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Yes
|
370
|
0.94 (0.69 to 1.28)
|
—
|
216
|
1.50 (0.89 to 2.56)
|
—
|
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No
|
311
|
|
|
223
|
|
|
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aThe age distribution of children <15
years of age was 7.2 (SD 3.9) with a range from 0 to 14 years and
that of older adolescents and adults was 30.6 (SD 13.9) with a range
of 15 to 85 years.
|
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bThe numbers differ based on completeness
of information for each variable.
|
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cOR, odds ratios; CI, 95% confidence
intervals.
|
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dAdjusted for glasses of liquid consumed
(continuous variable), distance from healthcare facility, date of
onset of symptoms, and thrombocytopenia.
|
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eThe adjusted OR and 95% CI for glasses
of liquid consumed (dichotomous variable) were obtained from a separate
model that adjusted for the same factors as footnote d.
|
| fAdjusted for glasses of liquid
consumed (continuous variable), date of onset of symptoms, and thrombocytopenia. |
| gThe adjusted OR and 95% CI
for glasses of liquid consumed (dichotomous variable) were obtained
from a separate model that adjusted for the same factors as footnote
f. |
|
h Dash indicates that this variable did
not significantly contribute to the multivariate model.
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