Hemolytic uremic syndrome risk and Escherichia coli O157:H7.We reviewed medical records of 238 hospitalized patients with Escherichia coli Escherichia coli (ĕsh'ərĭk`ēə kō`lī), common bacterium that normally inhabits the intestinal tracts of humans and animals, but can cause infection in other parts of the body, especially the urinary tract. O157:H7 diarrhea to identify risk factors for progression to diarrhea-associated hemolytic uremic syndrome hemolytic uremic syndrome n. A syndrome in which hemolytic anemia and thrombocytopenia occur with acute renal failure, marked in children by sudden gastrointestinal bleeding, urine that contains red blood cells and is scanty in volume, and (HUS). Data indicated that young age, long duration of diarrhea, elevated leukocyte count leukocyte count see White cell count , and proteinuria proteinuria /pro·tein·uria/ (-ur´e-ah) an excess of serum proteins in the urine, as in renal disease or after strenuous exercise.proteinu´ric pro·tein·u·ri·a n. 1. were associated with HUS. ********** In the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. , Escherichia coli O157:H7 causes [approximately equal to] 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 E. coli: see Escherichia coli. E. coli in full Escherichia coli Species of bacterium that inhabits the stomach and intestines. E. coli can be transmitted by water, milk, food, or flies and other insects. O157:H7 outbreaks, female sex, young age, elevated leukocyte count, antimicrobial drug use, vomiting, and fever have been reported as risk factors for HUS (3-11). 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 New York, state, United States New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of state surveillance system for post-diarrheal 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 case-control study, n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. . 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 communicable disease n. A disease that is transmitted through direct contact with an infected individual or indirectly through a vector. Also called contagious disease. Surveillance System (CDSS CDSS California Department of Social Services CDSS Clinical Decision Support Systems CDSS Country Dance and Song Society CDSS Canadian Down Syndrome Society CDSS Community Day Secondary Schools (Malawi) ) in 1998 and 1999 were reviewed according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. 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 Hemolytic Anemia Definition Red blood cells have a normal life span of approximately 90-120 days, at which time the old cells are destroyed and replaced by the body's natural processes. with microangiopathic changes, renal insufficiency renal insufficiency A defect in renal ability to 'clear' waste products, a sign of inadequate glomerular filtration (creatinine creatinine /cre·at·i·nine/ (kre-at´i-nin) an anhydride of creatine, the end product of phosphocreatine metabolism; measurements of its rate of urinary excretion are used as diagnostic indicators of kidney function and muscle mass. level [greater than or equal to] 1.0 mg/dL in a child <13 years of age or [greater than or equal to] 1.5 mg/dL in an adult, or [greater than or equal to] 50% increase over baseline), and thrombocytopenia Thrombocytopenia Definition Thrombocytopenia is an abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets. (platelet count Platelet Count Definition A platelet count is a diagnostic test that determines the number of platelets in the patient's blood. Platelets, which are also called thrombocytes, are small disk-shaped blood cells produced in the bone marrow and involved in <150,000/[micro]L). 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 (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System. software (SAS Institute SAS Institute Inc., headquartered in Cary, North Carolina, USA, has been a major producer of software since it was founded in 1976 by Anthony Barr, James Goodnight, John Sall and Jane Helwig. , Cary, NC, USA). A multiple logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors. 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 confidence interval, n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. [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 urinary tract infection (UTI), n infection in one or more of the structures that make up the urinary system. Occurs more often in women and is most commonly caused by bacteria. , otitis media Otitis Media Definition Otitis media is an infection of the middle ear space, behind the eardrum (tympanic membrane). It is characterized by pain, dizziness, and partial loss of hearing. , 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 hematuria Blood in the urine. It usually indicates injury or disease of the kidney or another structure of the urinary system or possibly, in males, the reproductive system. It may result from infection, inflammation, tumours, kidney stones, or other disorders. 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 [greater than or equal to] 13,000/[micro]L (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 Leukocytosis Definition Leukocytosis is a condition characterized by an elevated number of white cells in the blood. Description Leukocytosis is a condition that affects all types of white blood cells. at admission, and duration of diarrhea before hospitalization >3 days) were included in the multivariate analysis multivariate analysis, n a statistical approach used to evaluate multiple variables. multivariate analysis, n a set of techniques used when variation in several variables has to be studied simultaneously. . 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 [greater than or equal to] 13,000/mL (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 (3-5). 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 Antimicrobial agents Chemical compounds biosynthetically or synthetically produced which either destroy or usefully suppress the growth or metabolism of a variety of microscopic or submicroscopic forms of life. 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 prodrome /pro·drome/ (pro´drom) a premonitory symptom; a symptom indicating the onset of a disease.prodro´malprodro´mic pro·drome n. pl. <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 (5-8,14). Patients with leukocytes [greater than or equal to] 13,000/[micro]L at admission in our study had 5 times the risk of HUS. Protein and occult blood occult blood n. Blood that is present in amounts too small to be seen and can be detected only by chemical analysis or microscopic examination. Occult blood Presence of blood that cannot be seen with the naked eye. 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 [greater than or equal to] 13,000/[micro]L, 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. References (1.) Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C, et al. Food-related illness in the United States. Emerg Infect Dis. 1999;5:607-25. (2.) Dundas S, Todd WT, Stewart AI, Murdoc PS, Chaudhuri AKR AKR Auroral Kilometric Radiation AKR Vehicle Cargo Ship AKR Address Key Register AKR Anime Kingdom Rebirth , Hutchinson SJ. The central Scotland Escherichia coli O157:H7 outbreak: risk factors for hemolytic uremic syndrome and death among hospitalized patients. Clin Infect Dis. 2001;33:923-31. (3.) Griffin PM, Ostroff SM, Tauxe RV, Greene KD, Wells JG, Lewis JH, et al. Illnesses associated with E. coli O157:H7 infections: a broad clinical spectrum. Ann Intern Med. 1988;109:705-12. (4.) Griffin PM, Tauxe RV. The epidemiology of infections caused by E. coli O157:H7, other enterohemorrhagic E. coli and associated hemolytic uremic syndrome. Epidemiol Rev. 1991;13:60-98. (5.) Pavia AT, Nichols CR, Green DP, Tauxe RV, Mottile S. Hemolytic uremic syndrome during an outbreak of Escherichia coli O157:H7 infections in institutions for mentally retarded persons: clinical and epidemiologic observations. J Pediatr. 1990;116:544-51. (6.) Bell BP, Griffin PM, Lozano P, Christie DL, Kpbayashi JM, Tarr PI. Predictors of hemolytic uremic syndrome in children during a large outbreak of Escherichia coli O157:H7 infections. Pediatrics. 1997;100:E12. (7.) Ikeda K, Ida O, Kimoto K, Takatorige T, Nakanish N, Tatara K. Predictors for the development of haemolytic Adj. 1. haemolytic - relating to or involving or causing hemolysis; "hemolytic anemia" hemolytic uremic uremic pertaining to or emanating from uremia. uremic poisoning see uremia, visceral gout. uremic toxins syndrome with Escherichia coli O157:H7 infections: with focus on the day of illness. Epidemiol Infect. 2000;124:343-9. (8.) Kawamura N, Yamazaki T, Tamai H. Risk factors for the development of Escherichia coli O 157:H7 associated with hemolytic uremic syndrome. Pediatr Int. 1999;41:218-22. (9.) Carter AO, Borczyk AA, Carlson JA, Harvey B, Hockin JC, Karmali MA, et al. A severe outbreak of Escherichia coli O157:H7--associated hemorrhagic colitis hemorrhagic colitis n. Abdominal cramps and bloody diarrhea, without fever, attributed to a self-limited infection by a strain of Escherichia coli. in a nursing home. N Engl J Med. 1987;317:1496-1500. (10.) Cimolai N, Carter JE, Morrison BJ, Anderson JD. Risk factors for the progression of Escherichia coli O157:H7 enteritis enteritis (ĕn'tərī`tĭs), inflammation of the gastrointestinal tract. Acute enteritis is not usually serious except in infants and older people, in whom the accompanying diarrhea can cause dehydration through the loss of fluids. to the hemolytic uremic syndrome. J Pediatr. 1990;116:589-92. (11.) Rowe PC, Walop W, Lior H, Mackenzie AM. Hemolytic anemia after childhood Escherichia coli O157:H7 infection: are females at increased risk? Epidemiol Infect. 1991;106:523-30. (12.) Chang HH, Tserenpuntsag B, Kacica M, Smith PF, Morse DL. Hemolytic uremic syndrome in New York. Emerg Infect Dis. 2004; 10:928-31. (13.) Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. The risk of hemolytic-uremic syndrome Hemolytic-Uremic Syndrome Definition Hemolytic-uremic syndrome (HUS) is a rare condition that affects mostly children under the age of 10, but also may affect the elderly as well as persons with other illnesses. after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. 2000;342:1930-6. (14.) Buteau C, Proulx F, Chaibou M, Raymond D, Clermont MJ, Mariscalco MM, et al. Leukocytosis in children with Escherichia coli O157:H7 enteritis developing the hemolytic uremic syndrome. Pediatr Infect Dis J. 2000; 19:642-7. (15.) Joh K. Predictive indicators for progression to severe complications (hemolytic-uremic syndrome and encephalopathy encephalopathy /en·ceph·a·lop·a·thy/ (en-sef?ah-lop´ah-the) any degenerative brain disease. AIDS encephalopathy HIV e. anoxic encephalopathy hypoxic e. ) and their prevention in enterohemorrhagic Escherichia coli enterohemorrhagic Escherichia coli EHEC Any of the E coli serotypes–eg O29, O39, O145 that produces shiga-like toxins, causing bloody inflammatory diarrhea, evoking a HUS. See Escherichia coli O157:H7, Hemolytic uremic syndrome. infection. Nippon Rinsho. 1997;55:700-5. Boldtsetseg Tserenpuntsag, * Hwa-Gan Chang, ([dagger]) Perry F. Smith, * ([dagger]) and Dale L. Morse * ([dagger]) * University at Albany, Albany, New York For other uses, see Albany. Albany is the capital of the State of New York and the county seat of Albany County. Albany lies 136 miles (219 km) north of New York City, and slightly to the south of the juncture of the Mohawk and Hudson Rivers. , USA; and 1-New York State Department of Health, Albany, New York, USA Address for correspondence: Hwa-Gan Chang, New York State Department of Health, Coming Tower Building, Room 1143, Empire State Plaza The Governor Nelson A. Rockefeller Empire State Plaza (commonly known as simply the Empire State Plaza and less formally as The South Mall) is a complex of several state government buildings in downtown Albany, New York. , Albany, NY 12237, USA; fax: 518-474-4880; email: hgc04@health.state.ny.us Ms Tserenpuntsag is a DrPH student majoring in epidemiology at the State University of New York (body) State University of New York - (SUNY) The public university system of New York State, USA, with campuses throughout the state. at Albany. Her research interests include infectious disease Infectious disease A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. epidemiology.
Table 1. Characteristics of hospitalized Escherichia coli O157:H7
patients by HUS case status, New York, 1998-1999 *
Total (N = 238) HUS (n = 36)
Characteristic n (%) n (%)
Age (y)
0-4 34 (14) 18 (49)
5-14 52 (22) 6 (17)
15-65 96 (24) 6 (17)
>65 56 (40) 6 (17)
Sex
Female 147 (62) 25 (69)
Male 91 (38) 11 (31)
Outcome
Dead 7 (3) 5 (14)
Alive 231 (97) 31 (86)
Outbreak
Yes 49 (21) 15 (42)
No 189 (79) 21 (58)
Hospital stay (d)
>4 121 (51) 31 (86)
1-4 117 (49) 5 (14)
Bloody stool
Yes 203 (85) 30 (84)
No 35 (15) 6 (16)
Fever
Yes 71 (30) 19 (53)
No 167 (70) 17 (47)
Vomiting
Yes 96 (40) 14 (39)
No 142 (60) 22 (61)
Antimicrobial drug use
Yes 89 (37) 11 (31)
No 149 (63) 25 (69)
Proteinuria at admission
Yes 60 (25) 23 (64)
No 178 (75) 13 (36)
Hematuria at admission
Yes 80 (34) 23 (64)
No 158 (66) 13 (36)
Leukocyte count at admission
[greater than or equal
to] 13,000/[micro]L 119 (50) 29 (81)
<13,000/[micro]L 119 (50) 7 (19)
Duration of diarrhea before
hospitalization
>3 days 70 (29) 24 (67)
[less than or equal
to] 3 days 168 (71) 12 (33)
Non-HUS (n = 202)
Characteristic n (%) OR (95% CI)
Age (y)
0-4 16 (8) 4.9 (2.2-11.8)
5-14 46 (23) 1.1 (0.4-3.1)
15-65 90 (44) 0.6 (0.2-1.7)
>65 50 (25) 1.0
Sex
Female 122 (61) 1.5 (0.8-3.4)
Male 80 (39) 1.0
Outcome
Dead 2 (1) 16.1 (2.9-86.8)
Alive 200 (99) 1.0
Outbreak
Yes 34 (17) 3.6 (1.6-7.5)
No 168 (83) 1.0
Hospital stay (d)
>4 90 (45) 7.7 (2.8-20.6)
1-4 112 (55) 1.0
Bloody stool
Yes 173 (86) 0.8 (0.3-2.4)
No 29 (14) 1.0
Fever
Yes 52 (26) 3.2 (1.6-6.5)
No 150 (74) 1.0
Vomiting
Yes 82 (40) 0.9 (0.4-1.9)
No 120 (60) 1.0
Antimicrobial drug use
Yes 78 (38) 0.7 (0.3-1.5)
No 124 (62) 1.0
Proteinuria at admission
Yes 37 (18) 7.8 (3.6-17.0)
No 165 (82) 1.0
Hematuria at admission
Yes 57 (28) 4.5 (2.1-9.4)
No 145 (72) 1.0
Leukocyte count at admission
[greater than or equal
to] 13,000/[micro]L 90 (44) 5.2 (2.2-12.3)
<13,000/[micro]L 112 (56) 1.0
Duration of diarrhea before
hospitalization
>3 days 46 (23) 6.7 (3.1-14.6)
[less than or equal
to] 3 days 156 (77) 1.0
Characteristic p value
Age (y)
0-4 <0.001
5-14
15-65
>65
Sex
Female 0.33
Male
Outcome
Dead 0.001
Alive
Outbreak
Yes 0.01
No
Hospital stay (d)
>4 0.001
1-4
Bloody stool
Yes 0.77
No
Fever
Yes 0.009
No
Vomiting
Yes 0.84
No
Antimicrobial drug use
Yes 0.38
No
Proteinuria at admission
Yes <0.001
No
Hematuria at admission
Yes <0.001
No
Leukocyte count at admission
[greater than or equal
to] 13,000/[micro]L <0.001
<13,000/[micro]L
Duration of diarrhea before
hospitalization
>3 days <0.001
[less than or equal
to] 3 days
* HUS, hemolytic uremic syndrome, OR, odds ratio;
CI, confidence interval.
Table 2. Multiple logistic regression analysis of
risk factors associated with HUS, New York, 1998-1999 *
No. patients (%) No. controls (%)
Characteristic (n = 36) (n = 202)
Proteinuria 23 (64) 37 (18)
Duration of diarrhea
before hospitali-
zation >3 d 24 (67) 46 (23)
Age <5 y 18 (50) 16 (8)
Leukocytes >13,000/
[micro]L 29 (81) 90 (44)
Outbreak case 15 (42) 34 (17)
Hematuria 23 (64) 57 (28)
Fever 19 (53) 52 (26)
Characteristic Adjusted OR (95% CI)
Proteinuria 6.7 (1.9-24.1)
Duration of diarrhea
before hospitali-
zation >3 d 6.2 (2.2-17.4)
Age <5 y 5.9 (1.9-17.6)
Leukocytes >13,000/
[micro]L 4.4 (1.6-12.6)
Outbreak case 1.7 (0.6-4.9)
Hematuria 1.4 (0.4-4.9)
Fever 1.1 (0.4-3.1)
* HUS, hemolytic uremic syndrome; OR, odds ratio;
CI, confidence interval.
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