Rotavirus: A cause of nosocomial infection in the nursery

274

Clinical a n d laboratory observations

The Journal o f Pediatrics August 1982

Table. N e u t r o p h i l chemotaxis in t e r m and p r e t e r m infants at various ages after birth; values are expressed in m # of leading front (means and s t a n d a r d deviations) Gestational age at birth Term N Preterm > 34 wk N Preterm < 34 wk N Adult normal values N

Birth

Time o f regaining B W

A t 43 wk gestational age

39.4 _+ 13.7 10 46.7 _+ 9.8 11 51.6 +__ 15.2 7 98.7 _+ 11 89

84.6 _+ 9.3 10 51.3 _+ 17.3 11 49.4 _+ 17.2 7 98.7 +_ 11 89

-107.7 _+ 13.3 4 61.4 ___ 11.8 5 98.7 _+ 11 89

N = Number of subjects tested; BW = birth weighL p r e t e r m infants tested, all of whom h a d a gestational age at birth of > 34 weeks. C h e m o t a x i s remained defective in five of nine p r e t e r m infants tested, whose gestational age at birth was < 34 weeks. T h e s e data suggest t h a t the postnatal development of c h e m o t a c t i c proficiency is delayed in preterm newborn infants. T h e delay is more pronounced in infants born at less t h a n 34 weeks of gestational age, and m a y be related to the high frequency of infections in this group of neonates. The authors thank Prof. G. R. Burgio for his constant interest and support, Prof. A. G. Ugazio for stimulating discussions, Dr. V. Monafo for reading the paper, and Mrs. M. G. Corona for her excellent secretarial work.

4. 5.

6.

7. 8.

9.

REFERENCES 1. McCracken GH Jr, and Shinefield HR: Changes in the pattern of neonatal septicemia and meningitis, Am J Dis Child 112:33, 1966. 2. Smith RT, Platon ES, and Good RA: Septicemia of the newborn: current status of problem, Pediatrics 17:549, 1956. 3. Buetow KC, Klein SW, and Lame RB: The characteristic,

10.

11.

treatment and prevention of septicemia in premature infants, Am J Dis Child 110:29, 1965. Miller ME: Chemotactic function in human neonate: humoral and cellular aspects, Pediatr Res 5:487, 1971. Shigeoka AO, Santos JI, and Hill HR: Functional analysis of neutrophil granulocytes from healthy, infected and stressed neonates, J PEDIATR 95:454, 1979. Shigeoka AO, Charette RP, Wyman ML, and Hill HR: Defective oxidative metabolic responses of neutrophils from stressed neonates, J PEDIATR 98:392, 1981. Christensen DR, and Rothstein G: Efficiency of neutrophil migration in the neonate, Pediatr Res 14:1147, 1980. Laurenti F, Ferro R, Mazzetti G, Rossini M, and Bucci G: Neutrophil chemotaxis in preterm infants with infections, J " PEDIATR 96:468, 1980. Sacchi F, Ferrari FA, Fortunato A, Maggiore G, Marconi M, Pagani A, and Siccardi AG: A defect in neutrophil motility in two siblings with recurrent infections and a remarcable family history, Infection 7:45, 1979. Zigmond SM, and Hirsh JG: Leukocyte locomotion and chemotaxis: new methods for the evaluation and demonstration of cell derived chemotactic factors, J Exp Med 137:387, 1973. Saint-Anne Dergassies S: Le D~velopment du syst~me nerveux foetal, Berne, 1973, Documents scientifiques Guigoz Ed.

Rotavirus." A cause o f nosocomial infection in the nursery William J. Rodriguez, M.D., Ph.D.,* Hyun W. Kim, M.D., Carl D. Brandt, Ph.D., Anne B. Fletcher, M.D., and Robert H. Parrott, M.D., Washington, D. C.

From the Research Foundation o f Children's Hospital and the Department o f Child Health & Development o f The George Washington University School o f Medicine and Health Sciences. Supported in part by Grant No. ROI A I 17757-01 from NIAID, National Institutes o f Health. *Reprint address: Research Foundation of Children's Hospital, l 11 Michigan Ave., N.W., Washington, DC 20010.

A H 1G H I N C I D E N C E of rotavirus excretion in neonates has been reported in the U n i t e d Kingdom and Australia. 1-3 To our knowledge, no such neonatal H R V infection has-been reported to occur in nurseries in the U n i t e d States. 4 W e report the occurrence of H R V in a referral special care nursery during a period of rotavirus prevalence in the community, to emphasize potential control measures.

0022-3476/82/080274+04500.40/0@ 1982 The C. V. Mosby Co.

Volume 101 Number 2

Abbreviations used HRV: rotavirus LMW: loose mucoid watery ELISA: enzyme-linkedimmunosorbent assay EM: electronmicroscopy MATERIALS AND METHODS Patients admitted to a 36-bed, six-room referral nursery serving as a tertiary care center for the District of Columbia metropolitan area were included in the study. One or more stools from almost all nursery patients admitted from November, 1979, through May, 1980, were studied. Information on the infants' health status was collected each week day, and stools from all were routinely scheduled for collection on admission and between 5 AM and 3 PM on Monday and Wednesday. (Stools from patients admitted during the weekend were stored at - 2 0 ~ until the next working day). About 75% of the scheduled stool samples were collected. Stool characteristics were detected by the nursing personnel and were recorded by them as being normal (formed, seedy, or slightly yellow without excess water), loose (L), mucoid (M), or watery (W). For purposes of this paper, if one or more of the stools in a day were LMW, one to three such stools were collected and tested, or stored at minus 20~ or lower, and the patient was considered to have LMW stools that day. All stools were tested by rotavirus enzyme-linked immunosorbent assay J.6 Stools from symptomatic patients were tested for enteric viruses by direct electron microscopy6 and inoculated into two tube cultures each of monkey kidney, human embryo kidney, and HEP-2 cells.7 The ELISA-positive, EM-negative stool specimens were also tested by immune electron microscopy,6 and LMW stools were also tested for bacterial pathogens, including Salmonella, Shigella, toxigenic Escherichia coli, Campylobacter, and Yersinia. 8-~~ RESULTS During two periods of HRV infections in February and March, 1980, 275 serial fecal specimens from 102 nursery patients were examined for rotavirus by EM or ELISA. Rotavirus was detected by EM or ELISA in the stools of 22 (22%) of 102 babies. Rotavirus was also prevalent in the community at the same time. In the first "outbreak" (February 1 through 15), ten babies (aged 6 to 155 days) were infected, and the peak number of infections occurred nine days after the first demonstrated infection. Three of six nursery rooms eventually were involved. During the February outbreak, 40 of 60 patients in the entire nursery had at least one fecal

Clinical and laboratory observations

27 5

sample examined, and 25% of the 40 had HRV demonstrated in their stools by EM, immune EM, or ELISA. After discovery of the first infected patients, those with diagnosed or suspected HRV infection were isolated; the respective nursery rooms were closed to further admissions, and specific personnel were appointed to care for patients in an affected room. No further cases were identified from February 16 through March 3. The second period of HRV excretion occurred from March 4 through 31. A baby was admitted on March 3 with the diagnosis of failure to thrive and vomiting, and was placed in enteric isolation. His stools were found to be EM positive for HRV. Within 12 hours of admission, he was transferred to an isolation unit outside the nursery. A second patient admitted on March 3, 1980, because of poor feeding was not isolated. On his second hospital day he shed HRV in his stools and was transferred out of the nursery. A third patient, whose initial stool specimen on March 3 was negative for HRV by EM and ELISA, was found on March 7 to have a stool positive for HRV, though normal in frequency and consistency; five days later he developed L M W stools and he shed HRV through his twelfth hospital day. By March 18, patients in three nursery rooms had become infected. During the March outbreak, 62 of 83 nursery patients in all had serial fecal samples examined, and 12 of 62 (19%) had HRV in their stools. One final introduction of HRV into the nursery should be noted. A baby was discharged from the nursery on April 21 and re-admitted (free of enteric symptoms) on May 5, for inguinal hernia repair. As part of the routine screening of admissions, he was found (by EM) to be excreting HRV on May 6. This baby was isolated and was discharged from the nursery on May 8. No subsequent cases developed. No bacterial pathogens were recovered from any patient with HRV infection, nor were viruses other than HRV visualized or recovered. Of the 22 infected infants, HRV particles were visualized by EM or immune EM in all but one: in three serial samples from one baby, in two samples from seven babies, and in one sample from 13 babies; HRV was detected only by ELISA in one baby. All specimens positive by EM or immune EM were also positive by ELISA. In all, during the two outbreak periods, HRV was detected in 39 of 101 tested stools derived from 22 patients who shed HRV on at least one occasion. Moreover, HRV was found in 15 of 61 stools (25%) designated as LMW on the day of sampling and was found in 24 of 214 stools (11%) designated as normal. Infection was demonstrated in only three of the six nursery rooms. These three rooms (A, B, C) were designated outbreak rooms (Table I). The percentage of LMW stools obtained from HRV-positive patients was reported

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The Journal of Pediatrics August 1982

Table I. Characteristics of stools of nursery patients in relation to room assignment in the days around the time their stools were sampled for HRV Day from collection of specified stool No. of stools

Stool characteristics

Outbreak WABcroos 9 Yes 39

Norma L

Room

4 stoos Nonaffected rooms (128 stools)

HRV detected

Same day No. stools (% LMW)

f 538 8

No No

, 128t

+1 day No. stools (% LMW)

LMW Normal

++_2days No. stools (% LMW)

I 72 23 1659J 24 1130, *

17 (13) 111

27 (21) 101

38 90

I ll

*Includes 53 stools from HRV-negative patients who were in the affected rooms. ~'Includes 12 stools from patients who had H R V detected at some time during their hospital stay from stools obtained when they were not in the outbreak rooms. ~:P < 0.01.

w NS. I~'< 0.05. Table II. Characteristics of stools from 22 HRV-positive patients in relation to the day when stool was positive for HRV Days to or from detection of HRV in any specimen Stool characteristics

Same day patients positive (%)

+_1 day patients positive (%)

+_2 days patients positive (%)

Any LMW stools Only normal stools

10 (45) 12 (55)

14 (64) 8 (36)

15 (68) 7 (32)

to be significantly increased from 38% of 39 on the day virus first was detected to 72% of 39 _+ 2 days of such detection. However, the percentage of LMW stools in HRV-negative patients in the outbreak rooms also was reported increased, from 27 to 55% of 108, and LMW stools from patients in the nonaffected rooms increased from 13 to 30% of 128 over the same interval. There was no significant difference in the occurrence of LMW stools obtained from HRV-positive and -negative patients if the comparison was limited to the outbreak rooms. However, the frequency of LMW stools was greater in both HRVpositive and HRV-negative patients in the affected rooms as compared with those in the other rooms (Table I). Among the 22 HRV-positive patients, 45% had at least one or more L M W stools on the day their HRV-positive stools were collected (Table II). However, within _ 2 days from the day of diagnosis, 68% had one or more LMW stools. None of the neonates whose fecal sample contained HRV was sufficiently ill to require specific treatment for HRV disease. Vomiting, a classic symptom in HRV disease, was observed in only two infants at the time of infection. Although the patient population of our study nursery is hardly representative of the typical U.S. nurs-

ery, 41% of the 22 patients shedding HRV were between 6 and 17 days of age, and six of these youngest patients had L M W stools on the day they first were HRV positive. DISCUSSION Despite the high infection rate reported during neonatal HRV outbreaks, '-3 there has been a relatively low incidence of virus-related symptoms. Murphy and co-workers 2 reported diarrhea in 28% of 304 babies excreting HRV. Our findings support the view that newborn infants can be infected with HRV, that some have no symptoms, and that severe illness is not the rule. We observed that of 61 nursery patients with LMW stools on at least one day, 25% had HRV infection, whereas 75% had no evidence of such infection. Clearly, laboratory testing was required to ensure recognition of infected neonates. Although the initial source of the February infections remains unknown, the acquisition of viruses by babies at the beginning of the March outbreak was traceable in time to the admission of three nursery babies: one, a symptomatic infant; another, an infant with poor feeding; and a third infant with suspected sepsis. Fifty-five percent of babies infected during the two

Volume 101 Number 2

outbreaks had at least one stool found negative for HRV by EM or ELISA prior to developing infection. In at least two instances HRV was introduced into the nursery by an infected infant. Three other patients who may have introduced HRV were admitted with no diarrhea and nonspecific or subtle signs which led to a work-up to exclude the possibility of sepsis. They were not isolated initially. Such infants may represent particularly deceptive sources of HRV introduction into a nursery. Introduction of HRV by medical staff and nursery personnel also seems possible in view of previous reports of nosocomial spread? In keeping with the British experience,3 our nursery infections appeared near the peak of the epidemic of HRV in the community. However, ours disappeared as the community outbreak waned, whereas theirs continued (though at decreased levels) until the increase which accompanied the next community epidemic. We detected no HRV infection in neonates requiring the highest level of intensive care, who were housed in two rooms with six bassinettes nearby (nonoutbreak rooms, Table I). The policy for admission to these rooms was the same as that applied to other rooms in the nursery. However, in these rooms, visitors were restricted and there was essentially one-on-one nursing care, with the same staff regularly assigned to a particular baby. Particularly in special care nurseries, in which both transfer from other hospitals and prolonged stay are common, when HRV is prevalent in the community, we recommend the use of rapid methods of diagnosis, especially direct electron microscopy or ELISA, if possible, for screening nursery admissions from the community and for those who develop diarrhea. Once a nursery outbreak is demonstrated, we recommend screening of all nursery patients, cohorting of contacts, whether or not patients are shedding HRV in their stools, and restriction of staff movement (i.e., specific

Clinical and laboratory observations

277

assignment to suspect nursery room). These measures should aid in preventing further spread of the virus. Whether a "benign" HRV infection in the neonatal period results in "immunization" should be studied by prospective follow-up of such infected patients. REFERENCES

1. Bishop R, Cameron D, Baines G, et al: The etiology of diarrhea in newborn infants, in Elliott K, and Knight J, editors: Acute diarrhea in childhood, Ciba Foundation Symposium, Excerpta Medica, 1976, North Holland, Amsterdam, pp 223-231. 2. Murphy A, Albrey M, and Hay P: Rotavirus infection in neonates, Lancet 1:297, 1975. 3. Chrystie IL, Totterdell BM, and Banatvala JE: Asymptomatic endemic rotavirus infection in the newborn, Lancet 1:1176, 1978. 4. Steinhoff MC, and Gerber MA: Rotavirus infection of neonates, Lancet 1:775, 1978. 5. Yolken RH, Barbour B, and Wyatt RG: Enzyme-linked immunosorbent assay (ELISA) for identification of rotaviruses from different animal species, Science 201:259, 1978. 6. Brandt CD, Kim HW, Rodriguez WJ, et al: Comparison of direct electron microscopy, immune electron microscopy,and rotavirus enzyme-linked immunosorbent assay for detection of gastroenteritis viruses in children, J Clin Microbiol 13:976, 1981. 7. Kapikian A, Kim H, Wyatt R, et al: Human reovirus-like agent associated with "winter" gastroenteritis, N Engl J Med 294:965, 1976. 8. Sack D, and Sack RB: Tests for enterotoxigenic E. eoli using Y-I adrenal cells in minieultures, Infect Immun 11:334, 1975. 9. Gianella R: Suckling mouse model for detection of heat stable E. coli enterotoxin: characteristics of the model, Infect Immun 14:95, 1976. 10. Skirrow MB: Campylobacter enteritis, a "new" disease, Br Med J 2:9, 1977. 11. Middleton PJ, Szymanski MT, and Petrie M: Viruses associated with acute gastroenteritis in young children, Am J Dis Child 131:733, 1977.

Prevention of anemia and iron deficiency in very low-birth-weight infants Martti A. Siimes, M.D.,* and Anna-Liisa J~irvenp~i~i,M.D., Helsinki, Finland

From Children's Hospital, University o f Helsinki. Supported by grants from the Sigrid Juselius Foundation, Finland. *Reprint address: Children's Hospital, University of Helsinki, Stenb~ckinkatu 11, SF-00290 Helsinki 29, Finland.

0022-3476/82/080277+04500.40/0@ 1982 The C. V. Mosby Co.

THE INCREASING NUMBER of surviving very low-birthweight infants prompted us to analyze the age-dependent changes in concentration of hemoglobin and the effectiveness with which iron deficiency is prevented in this very rapidly growing group of patients.