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Hemolytic uremic syndrome risk and Escherichia coli O157:H7.
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PMID:  16485489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We reviewed medical records of 238 hospitalized patients with Escherichia coli O157:H7 diarrhea to identify risk factors for progression to diarrhea-associated hemolytic uremic syndrome (HUS). Data indicated that young age, long duration of diarrhea, elevated leukocyte count, and proteinuria were associated with HUS.
Authors:
Boldtsetseg Tserenpuntsag; Hwa-Gan Chang; Perry F Smith; Dale L Morse
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Emerging infectious diseases     Volume:  11     ISSN:  1080-6040     ISO Abbreviation:  Emerging Infect. Dis.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2006-02-20     Completed Date:  2006-03-16     Revised Date:  2012-09-19    
Medline Journal Info:
Nlm Unique ID:  9508155     Medline TA:  Emerg Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1955-7     Citation Subset:  IM    
Affiliation:
University at Albany, Albany, New York, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Age Factors
Aged
Case-Control Studies
Child
Child, Preschool
Diarrhea / complications,  microbiology
Escherichia coli Infections / complications*,  epidemiology,  microbiology
Escherichia coli O157*
Female
Hemolytic-Uremic Syndrome / complications*,  microbiology*
Humans
Infant
Leukocyte Count
Male
Middle Aged
Multivariate Analysis
Odds Ratio
Proteinuria
Risk Factors
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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Journal Information
Journal ID (nlm-ta): Emerg Infect Dis
Journal ID (iso-abbrev): Emerging Infect. Dis
Journal ID (publisher-id): EID
ISSN: 1080-6040
ISSN: 1080-6059
Publisher: Centers for Disease Control and Prevention
Article Information
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Print publication date: Month: 12 Year: 2005
Volume: 11 Issue: 12
First Page: 1955 Last Page: 1957
ID: 3367638
PubMed Id: 16485489
Publisher Id: 05-0607
DOI: 10.3201/eid1112.050607

Hemolytic Uremic Syndrome Risk and Escherichia coli O157:H7 Alternate Title:Hemolytic Uremic Syndrome Risk and E. coli O157:H7
Boldtsetseg Tserenpuntsag*
Hwa-Gan Chang
Perry F. Smith*
Dale L. Morse*
*University at Albany, Albany, New York, USA
New York State Department of Health, Albany, New York, USA
Correspondence: Address for correspondence: Hwa-Gan Chang, New York State Department of Health, Corning Tower Building, Room 1143, Empire State Plaza, Albany, NY 12237, USA; fax: 518-474-4880; email: hgc04@health.state.ny.us

In the United States, Escherichia coli O157:H7 causes ≈73,000 infections and 60 deaths annually (1). Infection progresses to hemolytic uremic syndrome (HUS) in 2% to 15% of cases (2). In studies of E. coli O157:H7 outbreaks, female sex, young age, elevated leukocyte count, antimicrobial drug use, vomiting, and fever have been reported as risk factors for HUS (311). Previously, a possible association between HUS and female sex, young age, and prolonged duration of diarrhea was shown in a study that evaluated the New York state surveillance system for postdiarrheal HUS (12). This report extends that study to investigate hospitalized patients with E. coli O157:H7 infection to assess potential risk factors for progression of infection to HUS by using a case-control study.


The Study

Medical charts of all persons who were hospitalized and reported with confirmed cases of E. coli O157:H7 to the New York State Department of Health's Communicable Disease Surveillance System (CDSS) in 1998 and 1999 were reviewed according to a standardized survey form. A HUS case was defined as occurring in a patient with acute diarrhea who was hospitalized with E. coli O157:H7 infection and in whom confirmed or probable postdiarrheal HUS developed. A confirmed HUS case was defined as occurring in a patient with a clear history of acute diarrhea who showed the following signs: hemolytic anemia with microangiopathic changes, renal insufficiency (creatinine level >1.0 mg/dL in a child <13 years of age or >1.5 mg/dL in an adult, or >50% increase over baseline), and thrombocytopenia (platelet count <150,000/μL). A probable HUS case was defined as occurring in a patient with acute diarrhea with all the above signs except microangiopathic changes in the blood smear. Controls were hospitalized patients with E. coli O157:H7 infection without HUS. Demographic, clinical, and laboratory characteristics were abstracted from medical charts. Statistical analysis was performed by using SAS software (SAS Institute, Cary, NC, USA). A multiple logistic regression analysis was performed to identify factors associated with development of HUS.

In 1998 and 1999, the CDSS received reports of 1,170 cases of E. coli O157: H7 infection. Of these, 255 patients (21%) were hospitalized and 238 (93%) had medical charts available for review. Thirty-six (15%) patients were confirmed (n = 29) or probable (n = 7) HUS case-patients, and 202 E. coli O157:H7–infected patients without HUS were identified as controls. The risk of HUS was highest among children <5 years of age, compared with patients >65 years (odds ratio [OR] 4.9, 95% confidence interval [CI] 2.2–11.8). Sixty-nine percent of HUS patients were female compared with 61% of controls (OR 1.5, 95% CI 0.8–3.4). The hospital stay was significantly longer for HUS patients than controls (median hospital stay 13 vs. 3 days). Five HUS patients (14%) died, including 2 children <5 years of age, compared with 2 controls (1%).

Forty percent of all patients had vomiting, and 85% had bloody stool. These factors were not significantly different between patients and controls. Eleven (31%) case-patients and 78 (38%) controls were treated with antimicrobial drugs (not significant). Antimicrobial treatment was reported in 11 patients before the diagnosis of HUS: 6 received antimicrobial drugs primarily for other conditions (e.g., urinary tract infection, otitis media, venous line sepsis), 1 had treatment stopped once E. coli O157:H7 was diagnosed, and we could not tell whether drug regimens were completed or discontinued in 4 patients. HUS patients were more likely than non-HUS controls to have fever (OR 3.2, 95% CI 1.6–6.5). The duration of diarrhea before hospitalization was significantly longer for HUS patients than for non-HUS controls (median 4 vs. 2 days).

Proteinuria and hematuria were observed significantly more often among the case-patients. Twenty-three (64%) patients had proteinuria at admission, whereas 37 (18%) controls were admitted with proteinuria (OR 7.8, 95% CI 3.6–17). Hematuria at admission was reported in 23 (64%) patients and 57 (28%) controls (OR 4.5, 95% CI 2.1–9.4). Twenty-nine (81%) HUS patients vs. 90 (44%) controls had leukocyte counts >13,000/μL (OR 5.2, 95% CI 2.2–12.3) at admission (Table 1). Factors associated with HUS in univariate analysis (age <5 years, outbreak case, fever, hematuria, proteinuria, leukocytosis at admission, and duration of diarrhea before hospitalization >3 days) were included in the multivariate analysis. The following variables were associated with HUS development in the multivariate analysis: proteinuria (OR 6.7, 95% CI 1.9–24.1), duration of diarrhea before hospitalization >3 days (OR 6.2, 95% CI 2.2–17.4), age <5 years (OR 5.9, 95% CI 1.9–17.6), and leukocyte count >13,000/μL (OR 4.4, 95% CI 1.6–12.6). Factors such as outbreak involvement, hematuria and fever were not associated with HUS development (Table 2).


Conclusions

This study provides additional information on potential risk factors for progression of E. coli O157:H7 infection to HUS, but unlike other studies, this study used hospitalized rather than outpatient controls. Our data confirmed previous differences in risk for HUS development by age group (35). Women and girls have been reported to be at increased risk for HUS development in several studies (10,11), but our study showed no significant increased risk. Several studies have suggested that administration of antimicrobial agents increases risk for HUS development (5,6,9,13), but no significant relationship was observed between HUS and the use of antimicrobial drugs in our sample.

Although reports (5,7) have demonstrated a higher incidence of HUS among patients with bloody diarrhea, fever, or vomiting, our multivariate analysis did not show a significant association between these characteristics and HUS. Since only hospitalized patients with severe diarrhea were studied, some symptoms (bloody stool, fever, or vomiting) might have been reported more often than in the general population with E. coli O157:H7 infection. As a result, some significant associations might have been missed. Buteau et al. (14) reported that a diarrheal prodrome <3 days is an independent predictor of HUS development in children with E. coli O157:H7 infection; however, our study suggested that prolonged diarrhea (>3 days) may increase the risk of HUS.

Our analysis was consistent with results of other studies that found patients with elevated leukocyte counts to be at higher risk for developing HUS (58,14). Patients with leukocytes >13,000/μL at admission in our study had 5 times the risk of HUS. Protein and occult blood in urine were described as risk factors for HUS in a study in Japan (15). In the current study, proteinuria at admission was also a risk factor for HUS. However, HUS had already developed in most of these patients by the time of hospitalization, and we could not determine whether these factors preceded HUS development.

In summary, patients hospitalized for E. coli O157:H7 infection, those <5 years of age with >3 days of diarrhea, leukocytes >13,000/μL, and proteinuria should be monitored closely for further complications. Nine (25%) of the HUS patients had 4 risk factors, 11 (31%) patients had 3 risk factors, and 10 (28%) had 2 risk factors. In comparison, none of the controls had these 4 risk factors, 4 (2%) had 3 risk factors, and 47 (23%) had 2 risk factors. Identifying potential risk factors may allow clinicians to develop treatment interventions to prevent progression to HUS.


Notes

Suggested citation for this article: Tserenpuntsag B, Chang H-G, Smith PF, Morse DL. Hemolytic uremic syndrome risk and Escherichia coli O157:H7. Emerg Infect Dis [serial on the Internet]. 2005 Dec [date cited]. http://dx.doi.org/10.3201/eid1112.050607

Ms Tserenpuntsag is a DrPH student majoring in epidemiology at the State University of New York at Albany. Her research interests include infectious disease epidemiology.


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Tables
[TableWrap ID: T1] Table 1  Characteristics of hospitalized Escherichia coli O157:H7 patients by HUS case status, New York, 1998–1999*
Characteristic Total (N = 238) n (%) HUS (n = 36) n (%) Non-HUS (n = 202) n (%) OR (95% CI) p value
Age (y)
0–4 34 (14) 18 (49) 16 (8) 4.9 (2.2–11.8) <0.001
5–14 52 (22) 6 (17) 46 (23) 1.1 (0.4–3.1)
15–65 96 (24) 6 (17) 90 (44) 0.6 (0.2–1.7)
>65 56 (40) 6 (17) 50 (25) 1.0
Sex
Female 147 (62) 25 (69) 122 (61) 1.5 (0.8–3.4) 0.33
Male 91 (38) 11 (31) 80 (39) 1.0
Outcome
Dead 7 (3) 5 (14) 2 (1) 16.1 (2.9–86.8) 0.001
Alive 231 (97) 31 (86) 200 (99) 1.0
Outbreak
Yes 49 (21) 15 (42) 34 (17) 3.6 (1.6–7.5) 0.01
No 189 (79) 21 (58) 168 (83) 1.0
Hospital stay (d)
>4 121 (51) 31 (86) 90 (45) 7.7 (2.8–20.6) 0.001
1–4 117 (49) 5 (14) 112 (55) 1.0
Bloody stool
Yes 203 (85) 30 (84) 173 (86) 0.8 (0.3–2.4) 0.77
No 35 (15) 6 (16) 29 (14) 1.0
Fever
Yes 71 (30) 19 (53) 52 (26) 3.2 (1.6–6.5) 0.009
No 167 (70) 17 (47) 150 (74) 1.0
Vomiting
Yes 96 (40) 14 (39) 82 (40) 0.9 (0.4–1.9) 0.84
No 142 (60) 22 (61) 120 (60) 1.0
Antimicrobial drug use
Yes 89 (37) 11 (31) 78 (38) 0.7 (0.3–1.5) 0.38
No 149 (63) 25 (69) 124 (62) 1.0
Proteinuria at admission
Yes 60 (25) 23 (64) 37 (18) 7.8 (3.6–17.0) <0.001
No 178 (75) 13 (36) 165 (82) 1.0
Hematuria at admission
Yes 80 (34) 23 (64) 57 (28) 4.5 (2.1–9.4) <0.001
No 158 (66) 13 (36) 145 (72) 1.0
Leukocyte count at admission
>13,000/μL 119 (50) 29 (81) 90 (44) 5.2 (2.2–12.3) <0.001
<13,000/μL 119 (50) 7 (19) 112 (56) 1.0
Duration of diarrhea before hospitalization
>3 days 70 (29) 24 (67) 46 (23) 6.7 (3.1–14.6) <0.001
<3 days 168 (71) 12 (33) 156 (77) 1.0

*HUS, hemolytic uremic syndrome; OR, odds ratio; CI, confidence interval.


[TableWrap ID: T2] Table 2  Multiple logistic regression analysis of risk factors associated with HUS, New York, 1998–1999*
Characteristic No. patients (%) (n = 36) No. controls (%) (n = 202) Adjusted OR (95% CI)
Proteinuria 23 (64) 37 (18) 6.7 (1.9–24.1)
Duration of diarrhea before hospitalization >3 d 24 (67) 46 (23) 6.2 (2.2–17.4)
Age <5 y 18 (50) 16 ( 8) 5.9 (1.9–17.6)
Leukocytes >13,000/μL 29 (81) 90 (44) 4.4 (1.6–12.6)
Outbreak case 15 (42) 34 (17) 1.7 (0.6–4.9)
Hematuria 23 (64) 57 (28) 1.4 (0.4–4.9)
Fever 19 (53) 52 (26) 1.1 (0.4–3.1)

*HUS, hemolytic uremic syndrome; OR, odds ratio; CI, confidence interval.



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