Norwalk like Gastroenteritis Epidemic in Toronto Hospital

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					                 Norwalk-like Gastroenteritis Epidemic in a Toronto Hospital
                  WOLF-DIETRICH LEERS, MD, PHD, GEORGE KASUPSKI, PHD, RICHARD FRALICK, MD,
                    SIMONE WARTMAN, RN, JOHN GARCIA, MSC, AND WILLIAM GARY, MPH, DRPH

     Abstract: An epidemic of gastroenteritis in a teaching hospital          symptoms were typical of Norwalk gastroenteritis, and Norwalk-like
affected 57 patients and 69 staff over a 26-day period. The index case        virus particles, serologically different from the prototype Norwalk
was a patient admitted with acute abdominal pain and diarrhea two             virus strain, were observed in 17 of 20 fecal specimens examined by
days prior to the outbreak. The epidemic curve indicated person-              immune-electron microscopy. (Am J Public Health 1987;
to-person transmission. The incubation period, duration and types of          77:291-295.

Introduction                                                                  other units. Wards were reopened after no new cases had been
     Norwalk and Norwalk-like viruses are the major cause of                  noted for a period of 72 hours. Discharge of patients was
acute nonbacterial gastroenteritis in adults. Epidemics of                    permitted 48 hours after cessation of their symptoms.
gastroenteritis caused by these viruses have been reported in                 Laboratory Investigations
nursing homes, schools, and recreational settings. 1-5 The exact                    Fecal specimens and food samples taken from the index
mode of transmission is unclear. Water-borne, food-borne, and                 floor were processed on routine bacteriological media for the
person-to-person transmission have all been implicated in                     detection of enteropathogenic bacteria. Initially, fecal spec-
epidemics,"'4 and the results of volunteer studies suggest                    imens were also examined for ova and parasites. Fecal
fecal-oral transmission.1'516 We describe an epidemic caused by               specimens for virology were obtained from 20 patients within
a Norwalk-like virus in a teaching hospital.                                  the first 48 hours of their illness. Ten per cent suspensions
                                                                              prepared from them were innoculated on to monolayer
Methods                                                                       cultures of primary rhesus monkey kidney, a human embry-
Description, Investigation and Control of the Outbreak                        onic lung fibroblast line (MRC 5 cells), and an adeno-virus
     The Wellesley Hospital is a 600-bed, tertiary care hos-                  type 5 transformed line of human embryonic kidney cells (293
pital affiliated with the University of Toronto. On Easter                    cells) sensitive to fastidious enteric adenoviruses. The inoc-
Monday morning, April 3, 1983, seven patients and nine                        ulated cultures were observed for the development of
nurses on a pulmonary diseases ward (3 North) were reported                   cytopathic effects for two passages. Intracerebral innocula-
to be ill with acute gastroenteritis. The outbreak then spread                tion of suckling mice was not done for coxsackie A viruses.
to involve both patients and staff in seven wards on three                         Electron microscopy (EM) and immune electron micros-
floors during the 26-day duration of the outbreak.                            copy (IEM) for virus particles were performed on 10 per cent
     Cases were defined as persons having any two of either                   stool filtrates as described elsewhere. 18 A convalescent
diarrhea, abdominal cramps, vomiting and/or nausea; a                         serum specimen obtained from the index case on the ninth
thorough epidemiologic investigation was instituted. A short                  day after onset of symptoms was used as the source of "virus
one-page questionnaire was administered to the first 20                       specific" antibodies for IEM. Stool filtrates were tested for
symptomatic cases to assist us in determining the likely                      the presence of Norwalk virus antigen by biotin-avidin
source and mode of transmission of the outbreak. The                          immunoassay (BAI).'9
infection control nurse made daily rounds throughout the                           Acute and convalescent phase serum specimens were
hospital to locate new cases and to monitor compliance with                   obtained from six patients within 48 hours of the onset of
control measures.                                                             symptoms and seven to nine days later, respectively. IEM for
     All affected patients were placed on "enteric precau-                    virus specific antibody was performed at a screening dilution
tions" ;17 staff members with symptoms of gastroenteritis                     of 1:50 using a "virus positive" stool filtrate as a source of
were excluded from work until asymptomatic for at least 48                    antigen. The paired sera were tested for rises in antibody titer
hours; visits by friends and relatives to affected patients were              to Norwalk virus by both radio-immunoassay (RIA) and
restricted; patients were asked to contact the hospital if they               biotin-avidin immunoassay (BAI).'9'20
became ill after discharge; personal hygiene and handwash-                    Results
ing were emphasized.
     Wards were closed when a cluster of two to three cases                        A total of 126 people (57 patients and 69 staff) were found
occurred on a previously unaffected floor. Transfer of patients               to meet the case definition. The majority of cases among staff
from closed wards was only permitted when they had recovered                  were nurses (45/69), followed by medical staff (1 1/69). Attack
from gastroenteritis for 48 hours. Patients were not allowed to               rates were similar in patients (27.7 per cent) and nurses (27.3
leave closed units for tests, surgery, etc., unless absolutely                per cent), and in male (25.9 per cent) and female (29.8 per
necessary, and the nursing staff was not permitted to work on                 cent) patients, although there was a considerable variation
                                                                              among the rates by ward. Statistical analysis did not show a
     From the Department of Microbiology, Wellesley Hospital, University of   clear association of rate of illness with age.
Toronto; Department of Public Health, City of Toronto; and the Centers for         The frequency of symptom expression among cases is
Disease Control, Atlanta, GA. Address reprint requests to Wolf-Dietnch        presented in Figure 1. Among all cases, 114 (90.5 per cent)
Leers, MD, PhD, Chief, Department of Microbiology, Wellesley Hospital, 160    had diarrhea; 73 (57.9 per cent) vomiting; 34 (27.0 per cent)
Wellesley Street, East, Toronto, Ontario, Canada, M4Y IJ3. This paper,        abdominal pain; and 12 (9.5 per cent) nausea only. Fever and
submitted to the Journal May 12, 1986, was revised and accepted for
publication July 24, 1986.                                                    respiratory symptoms were absent. Acute illness lasted about
                                                                              24 hours, and recovery was complete within 48-72 hours.
C 1987 American Journal of Public Health 0090-0036/87$1.50                         The index case was found to be a female patient with

AJPH March 1987, Vol. 77, No. 3                                                                                                             291
LEERS, ET AL.

      Patients
                       Diarrhea
                       Vomiting
              Abdominal pain
                  Nausea only

      Staff                         I
                       Diarrhea
                       Vomiting
                                        --
              Abdominal pain
                  Nausea only
                                                            I       I       I         I      I       I      I        I       1      I

                                           5       10      15      20      25       30       35     40     45       50      55     60      65
                                                                                  Frequency
      FIGURE 1-Frequency of Symptom Expression among Cases during Gastroenteritis Outbreak

                     14
                     13 _                                                                                Numbe
                     12         2                                                                        Numb5


                     10




       Number          8

             of
         Cases
                     6~~~~~~.
                        I~~~~~~a
                        I




                                                                                                                20 21 22 23 24 25 26



chronic asthma who had become ill with acute abdominal                          developing within the first eight days of the 26-day outbreak.
pain and diarrhea one day prior to admission to hospital.                       Separate epidemic curves for the two floors of the hospital on
There was a history of diarrhea in a friend who became ill two                  which the majority of patient cases occurred are presented in
days after the index case. Based on the time interval between                   Figure 3. On the third floor, which contained the index ward,
admission of the index case and the next hospital case, the                     cases accumulated most rapidly during the fourth through
incubation period was estimated to be 24-48 hours.                              seventh days of the outbreak while, on the fourth floor, peak
     The epidemic curve of the number of cases among                            numbers of cases among patients occurred on days eight
patients and staff (Figure 2) is consistent with a propagated                   through ten. In general, cases appeared earlier in staff than in
rather than a point-source type of outbreak, and illustrates a                  patients on both floors.
relatively abrupt onset of illness with 50 per cent of the cases                     Follow-up by public health staff with the likely sources

292                                                                                                              A2JPH March 1987, Vol. 77, No. 3
                                                                                                NORWALK-LIKE GASTROENTERITIS EPIDEMIC


                     7                                                                                                     3rd Floor
                     6
                     5
                     4
                     3
                     2

     Number
          of              1 2 3 4 5 6 7 8 9 1011 121314151617181920212223242526
      Cases          8
                     7                                                                                                     4th Floor
                     6
                     5
                     4
                     3
                     2


                          1   2 3 4 5 6 7 8 9 10 11 12 13 14 1516 17 1819 20 2122 23 24 25 26
                                                                                 Day
     FIGURE 3-Number of Cases among Patients by Hospital Floor during 26-Day Norwalk-like Gastroenteritis Outbreak

of food for the index case and one friend, who also became                    enteric precautions, and the immediate removal of staff from
ill, proved negative. Food samples from the index ward and                    duty when gastroenteritis symptoms were reported. Al-
fecal specimens from acutely ill cases were negative for                      though our epidemic lasted longer than others described in
Salmonella, Shigella, Yersina enterocolitica, Campy-                          the literature,4 the composite epidemic curve is typical of an
lobacter, and Ova and Parasites.                                              epidemic propagated by person-to-person contact. Seventy-
      Virus-like particles were seen in four of the 20 fecal                  five per cent of all cases occurring during the first three days
suspensions examined by direct electron microscopy. The                       of the outbreak were in staff, suggesting that they served as
particles were 25 to 30 nanometers (nm) in diameter and                       vectors for propagation of the outbreak within the index
resembled parvo-piconaviruses in gross morphology. The                        floor. Subsequent spread to wards on the fourth floor, which
virus particles formed aggregates (Figure 4) when immune-                     occurred three to four days later, was also likely mediated by
electron microscopy (IEM) was performed on "virus posi-                       infected nursing staff, some of whom worked on several
tive" stool filtrates, using a convalescent serum specimen                    wards during a single shift and shared common lounge
from the index case as a source of virus specific antibodies.                 facilities and the cafeteria with colleagues from different
We found aggregates of virus particles in 17 of 20 filtrates                  areas. A similar transfer of infection between nursing staff
examined by IEM, establishing the presence of the virus on                    and patients has been documented in an nosocomical out-
each of the wards affected during the outbreak (Table 1).                     break of gastroenteritis which occurred in a nursing home.9
Norwalk virus antigen was not detected in any of the four                          The symptoms, incubation period, duration of illness,
IEM positive stool filtrates tested by BAI.                                   and pattern of spread all suggest that a Norwalk-like agent
      When IEM for virus specific antibody was performed
with a virus positive stool filtrate as a source of antigen,
seroconversion was evident in four of the six serum pairs                     TABLE 1-Immunoelectronmicroscopy of Acute Phase Stool Specimens
which were available for study. No change in the titer of                              from Patients with Epidemic Gastroenteritis
antibodies to Norwalk virus was found by either RIA or BAI                      Ward           Number of Stools Examined
in three of the IEM positive serum pairs. Seroconversion to                                                                  Virus Particles Present
Norwalk virus was demonstrated in the fourth serum pair by                    3Nonly                        7                           6
both methods, although with a low convalescent titer (1:200).                 3Sonly                        4                           3
Discussion                                                                    3 E only                      2                           2
                                                                              4 N only                      2                           2
      Rapid spread of the epidemic occurred in spite of closure               4Sonly                        2                           2
                                                                              4 Eonly                       3                           2
of several wards, restrictions in the movement of patients                    TOTAL                        20                          17
within the hosptial, enforced handwashing and hygiene,

AJPH March 1987, Vol. 77, No. 3                                                                                                                293
LEERS, ET AL.




                        *.   :            :.',   *   :   ';




                       FIGURE 4-Immune Electron Micrograph of Aggregated Virus Particles (x 239,400)

was responsible for our outbreak. This hypothesis was                     response in the four of the six patients from who paired sera
supported by the observation of parvo-picornavirus like                   were available.
particles in a few of the stool specimens examined, and the                    The etiologic agent of our outbreak resembles the
absence of any other microbiologic findings.                              Ditchling,2' Hawaii,22 and Marin County22 agents in that it is
     Immune electron microscopy, using convalescent sera                  morphologically similar to, but serologically distinct from,
and acute phase stool specimens as sources of virus-specific              the Norwalk agent.'8 The relationship, if any, between our
antibodies and antigens, respectively, has been used to                   agent and other reported Norwalk-like agents of
identify Norwalk-like agents in earlier outbreaks of winter               gastroenteritis remains to be determined.
vomiting disease and gastroenteritis which occurred in
Ditchling, England2' and Marin County, California.22 Using                                         ACKNOWLEDGMENTS
a similar approach, we were able to demonstrate a Norwalk-                     The investigation and control of the epidemic required cooperation of
like agent with high frequency in the stools of acutely ill               many people. We are unable to list them all, but following are those who were
patients, and to establish the presence of the agent on each              closely involved: Dr. L. Bertram, W. Miller, T. Natale, J. Stehle, M. Sweeney,
                                                                          W. Tennant. The advice of Dr. A.Z. Kapikian is gratefully acknowledged. This
of the wards affected in the outbreak. Infection with the agent           paper was presented in part at the 51 st Conjoint Meeting of Infectious Diseases
was further confirmed by the demonstration of a serologic                 in Montreal, Quebec, Nov. 29-Dec. 2, 1983.


294                                                                                                              AJPH March 1987, Vol. 77, No. 3
                                                                                                        NORWALK-LIKE GASTROENTERITIS EPIDEMIC

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               I                                                         ERRATUM

                    There is an error in the title of one of the late-breaking resolutions, published in the January 1987
               issue of the Journal on page 114. The title should read, "Irrational Response to the Fear of the Spread
               of the Virus that Causes AIDS." We regret the error.




AJPH March 1987, Vol. 77, No. 3                                                                                                                               295