Vol. 18, No. 1JOURNAL OF CLINICAL MICROBIOLOGY, JUlY 1983, P. 71-780095-1137/83/070071-08$02.00/0Copyright © 1983, American Society for Microbiology

Pediatric Viral Gastroenteritis During Eight Years of StudyCARL D. BRANDT,12t* HYUN WHA KIM, 1'2 WILLIAM J. RODRIGUEZ, 1'2 JULITA 0. ARROBIO,'BARBARA C. JEFFRIES,1 EMMA P. STALLINGS,1 CAROLYN LEWIS,1 AUDREY J. MILES,1

ROBERT M. CHANOCK,2'3 ALBERT Z. KAPIKIAN,2'3 AND ROBERT H. PARROTT2Research Foundation of Children's Hospital National Medical Center' and Department of Child Health andDevelopment, George Washington University School of Medicine and Health Sciences,2 Washington, D.C.

20010; and Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases,Bethesda, Maryland 202053

Received 22 December 1982/Accepted 25 March 1983

During the period January 1974 through July 1982, fecal samples from 1,537pediatric inpatients with gastroenteritis were tested for enteric viruses by electronmicroscopic and rotavirus enzyme-linked immunosorbent assay techniques. Rota-viruses were detected in 34.5% of these patients, enteric adenoviruses were

detected in 4.7%, -27-nm viruses were detected in 1.6%, and at least one of theseagents was found in 40.1% of the study subjects. Three infections were by an

apparently new agent which morphologically is a rotavirus, but which failed toreact in the rotavirus enzyme-linked immunosorbent assay. During the first 8calendar years of study, rotaviruses were detected in 39.0% of 577 patients in theeven-numbered years and 30.3% of 702 patients in the odd-numbered years.

Adenoviruses were found in all calendar months. Rotaviruses were found ininpatients in November through July, whereas -27-nm viruses were found inOctober through June. The percentage of patients who had a demonstrated viralinfection rose steadily from 7.4% in September to 72.0% in January and thensteadily declined to 2.9% in August. Viral infection was especially common instudy subjects who were 7 through 24 months of age; 61% of such children hadone or more enteric viruses. Rotavirus-infected patients tended to be younger

during the months of greatest rotavirus activity than at the beginning and end ofthe rotavirus season, presumably because of a greater exposure to virus at theheight of the rotavirus outbreak.

In recent years, previously unrecognized rota-viruses, adenoviruses, and miscellaneous, most-ly small (-27-nm) viruses have been detectedand associated with gastroenteritis (5, 8, 12, 13,16, 17, 19, 21, 23, 27, 29; M. Santosham, R.Yolken, C. Stockton, L. Benson, and R. Black,Program Abstr. Intersci. Conf. Antimicrob.Agents Chemother. 22nd, abstr. no. 897, 1982).Published studies tend to describe the epidemi-ology of these agents during relatively briefstudy periods and thus do not fully reflect theoccurrence of long term trends and variations.This report amplifies on certain of our previousobservations with these agents (2, 3, 5, 12, 23)and concentrates on epidemiologic patterns ofinfection in infants and young children withacute gastroenteritis during 96 consecutivemonths of study. By virtue of the great impor-tance of rotaviruses as a cause of pediatricgastroenteritis, this paper especially emphasizesfindings relevant to rotavirus infection.

t Reprint requests should be directed to C. D. Brandt,Research Foundation of Children's Hospital National MedicalCenter, 111 Michigan Avenue, N.W., Washington, DC 20010.

MATERIALS AND METHODSThe study population included most infants and

young children who were hospitalized at Children'sHospital National Medical Center with diarrhea orvomiting (or both) of 4 days' duration or less, begin-ning on 16 January 1974. Diagnostic fecal samplesfrom these patients generally were obtained on thefirst or second hospital day. Stools and diaper scrap-ings and some rectal swab specimens usually weretested for viruses by direct electron microscopy (EM)(3). Specimens negative or untested by direct EM weretested by immune EM (IEM) (3, 13). In addition, allspecimens were tested by a sensitive rotavirus group-specific enzyme-linked immunosorbent assay(ELISA) procedure (3, 13). Additional details of ourstudy methods and findings have been presented else-where (2, 3, 5, 12, 23).

RESULTSOverview of virus detection. In the period

January 1974 through July 1982, one or morefecal samples from 1,537 pediatric patients whowere hospitalized with acute gastroenteritis atthis medical center were tested for enteric virus-es by EM and rotavirus ELISA techniques.

71

on Septem

ber 8, 2020 by guesthttp://jcm

.asm.org/

Dow

nloaded from

72 BRANDT ET AL.

Overall, rotaviruses were detected in 530(34.5%) of the study patients, adenoviruses were

detected in 73 (4.7%), -27-nm viruses weredetected in 24 (1.6%), and at least one of theseagents was detected in 616 (40.1%) of the totalgroup of gastroenteritis patients.

All inpatients who were found rotavirus posi-tive by the ELISA also were found (after someretesting and a few lengthy EM readings) to berotavirus positive by EM or IEM. Specimensfrom two study patients in February 1981 andanother in March 1982 contained particles whichmorphologically were rotaviruses (and werecounted as rotaviruses for the purposes of thispaper), but which repeatedly failed to react toELISA positivity for rotavirus.

In the remainder of this paper, unless other-wise noted, data will be presented for the 8calendar years from January 1974 through De-cember 1981.

Enteric viruses by calendar year. On a yearlybasis, between 28.8 and 43.1% of all gastroenter-itis inpatients studied were rotavirus positive,1.4 to 10.7% were adenovirus positive, 0 to 4.9%were -27-nm virus positive, and at least one ofthese agents was present in 33.7 to 48.6% of allgastroenteritis inpatients tested (Table 1).A type of periodicity is evident in Table 1, in

that in each of the odd-numbered calendaryears, the percentage of gastroenteritis inpa-tients with a rotavirus infection was lower thanin the preceding even-numbered year. Overall,there was a statistically significant excess ofrotavirus infections (39.0 versus 30.3%) andtotal virus infections (44.5 versus 37.0%) in theeven-numbered calendar years as comparedwith the odd-numbered calendar years. A nearlysignificant excess of -27-nm virus infections

was also seen in the even-numbered calendaryears. Adenovirus infections were increased,but not significantly so, in the odd-numberedyears.

Enteric viruses by month. The regularity of theannual waves of rotavirus infection in this localecan be seen in Fig. 1, which includes datathrough July 1982. Rotavirus infections were

detected in inpatients during 55 (53%) of the 103illustrated months, and as many as 39 patientswere hospitalized with rotavirus infection in onestudy month (January 1981). Among all individ-uals tested (including children and adults nototherwise described in this paper) rotaviruseswere first detected each year between 22 Octo-ber and 22 December, their activity peaked inJanuary or February, and these viruses last wereseen between 25 April and 16 July. Rotaviruseswere never found in inpatients in August, Sep-tember, or October and were seen in July only in1982. Although not shown in Fig. 1, adenovirus-es were detected in from one to five inpatientsduring 47 (46%) of the 103 illustrated months,whereas -27-nm viruses were found in from oneto three inpatients in 20 (19%) of these studymonths.When data from the first 96 months of study

were combined, the proportion of gastroenteritisinpatients in whom an enteric virus was demon-strated by EM, IEM, or rotavirus ELISA rosesteadily from 7.4% in September to a peak of72.0% in January and then steadily declined to2.9% in August (Table 2). Over two-thirds of allgastroenteritis patients in January were rota-virus positive, and more than two-thirds of thedetected rotavirus infections occurred in Janu-ary and February. Adenovirus infections werefound year round, but were least evident in

TABLE 1. Virus infections in gastroenteritis inpatients during 8 successive years'

No. No. (%) with indicated infectionCalendar year tetd°2-mlCalendaryeartested Rotavirus Adenovirus v27-n Totaib

1974 80 32 (40.0) 3 (3.8) 0 (0.0) 34 (42.5)1975 103 34 (33.0) 11 (10.7) 2 (1.9) 45 (43.7)1976 144 62 (43.1) 2 (1.4) 7 (4.9) 70 (48.6)1977 153 44 (28.8) 10 (6.5) 0 (0.0) 54 (35.3)1978 166 62 (37.3) 10 (6.0) 4 (2.4) 73 (44.0)1979 175 51 (29.1) 6 (3.4) 2 (1.1) 59 (33.7)1980 187 69 (36.9) 10 (5.3) 4 (2.1) 80 (42.8)1981 271 84 (31.0) 15 (5.5) 4 (1.5) 102 (37.6)

Odd-year total 702 213 (30.3)c 42 (6.0) 8 (1.1)d 260 (37.0)eEven-year total 577 225 (39.0)c 25 (4.3) 15 (2.6)d 257 (44.5)eOverall total 1,279 438 (34.2) 67 (5.2) 23 (1.8) 517 (40.4)

a The study began on 16 January 1974.b Total with at least one infection; dual infections account for mathematic discrepancies.C 2 = 10.5, P < 0.005.d x2 = 3.82, P = 0.051.e x2 = 7.4, P < 0.01.

J. CLIN. MICROBIOL.

on Septem

ber 8, 2020 by guesthttp://jcm

.asm.org/

Dow

nloaded from

PEDIATRIC VIRAL GASTROENTERITIS 73

70-

60-

50-

a

` 40-

10E 30-Ez

20-

10-

* = Rotavirus PositiveO = Rotavirus Negative

*dhn1979

ol~~~~~~~~~~~~~rJ.LLLLWIUELJL.LL LL MLLL-L LL...1 974 1 1975 1 1976 1977 l 1978 1981 1 1982

July 1982 (as

1980

Year

FIG. 1. Rotavirus infections in patients with gastroenteritis from January 1974 throughdemonstrated by EM, IEM, and rotavirus confirmatory ELISA).

February, July, and August. With but two ex-ceptions, -27-nm virus infections were com-pletely absent from July through November,months when the conventional enteroviruses(also -27 nm in size) tend to be most common inthis community.

Rotavirus infections in subpopulations. Ourstudy subjects included patients from quite di-verse socioeconomic levels, including manychildren from the poorer areas of Washington,D.C. (which have predominantly black popula-tions) and others from the affluent suburbs(which have predominantly nonblack popula-tions). Among groups of inpatients who wereidentified retrospectively on the basis of race,the epidemiology of enteric virus infection dif-fered quite markedly.For example, rotavirus infections tended to

begin, peak, and decline earlier in the epidemicseason among those who were black (Table 3).There was a January epidemic peak amongblacks and a February peak for nonblacks. As aresult of the changing share of detected infec-tions that came from each of these subpopula-tions, the percentage of nonblacks with rota-virus infection increased.from 26% (11 of 42)hospitalized with rotavirus infection in all ofNovember and December to 35% (102 of 295)hospitalized in January and February and 46%(46 of 101) hospitalized in March through June(Table 3). Overall, 53% of nonblack and 39% ofblack inpatients studied had evidence of rota-virus infection.

Age, race, and sex. Viral infection was espe-cially common in the 483 study subjects whowere 7 through 24 months of age; 266 (55%) ofthese children had a rotavirus infection, and 298

(62%) had at least one enteric virus (Table 4).The number of detected enteric viral infec-

tions tended to be comparatively high in blackpatients in the first 6 months of life and innonblack patients after 12 months of age (Table5). For example, in the 0- through 3-month agegroup only 7 (11%) of 64 patients with rotavirusinfection were nonblack, whereas in those 13through 18 months of age, 37 (61%) of 61 withsuch infection were nonblack. Also, only 53(19%o) of 279 rotavirus infections in black pa-tients as compared with 81 (51%) of 159 innonblack patients occurred in those who wereover 12 months of age. The highest percentageof black patients in any 6-month age group whohad rotavirus infection, 52% (113 of 217), or anyenteric viral infection, 59% (128 of 217), oc-curred in those who were 7 through 12 months ofage. Among nonblacks, the comparable peakswere 82% for rotaviruses and 91% for any virus-es at 13 through 18 months of age.Males comprised 57% of our study popula-

tion, but the percentages of patients who hadinfections and the median age of those infectedwere quite similar for both sexes and withinracial groups (Table 6). However, in every pa-tient category, infected black children had alower median age than nonblack children withthe same type of virus.

Variation in patient age during rotavirus out-breaks. During January through March, themonths of greatest rotavirus activity, rotavirus-infected inpatients with gastroenteritis tended tobe somewhat younger than comparable patientsduring the other study months (Table 7). Thispresumably reflects a greater exposure of sus-ceptible individuals to virus, with a greater

1-IT-

I.

rFT-

VOL. 18, 1983

I=

on Septem

ber 8, 2020 by guesthttp://jcm

.asm.org/

Dow

nloaded from

TABLE 2. Virus infections in gastroenteritis inpatients, by calendar month (January 1974 through December1981)

Month No. No. (%) with indicated infectiontested Rotavirus Adenovirus -27-nm virus Totala

September 81 0 (0) 6 (7.4) 0 (0) 6 (7.4)October 45 0 (O)b 4 (8.9) 1 (2.2) 5 (11.1)November 69 10 (14.5) 7 (10.1) 1 (1.4) 18 (26.1)December 97 32 (33.0) 7 (7.2) 2 (2.1) 40 (41.2)January 250 168 (67.2) 9 (3.6) 7 (2.8) 180 (72.0)February 219 127 (58.0) 3 (1.4) 6 (2.7) 133 (60.7)March 142 65 (45.8) 8 (5.6) 2 (1.4) 74 (52.1)April 100 25 (25.0) 5 (5.0) 1 (1.0) 29 (29.0)May 71 10 (14.1) 6 (8.5) 2 (2.8) 18 (25.4)June 75 1 (1.3) 8 (10.7) 1 (1.3) 10 (13.3)July 60 0 (0)C 2 (3.3) 0 (0) 2 (3.3)August 70 0 (0) 2 (2.9) 0 (0) 2 (2.9)

a See footnote b of Table 1.b Rotavirus infections were found in two outpatients with diarrhea in October 1979.c Two rotavirus infections occurred in July 1982.

chance of early infection, at the height of therotavirus outbreak. The change in age was espe-cially evident in black study subjects. Suchinfected patients had a median age in Januarythrough March of 7 months as compared with9.5 months in the remaining study period. Fur-thermore, during January through March, as

compared with the remaining study months, asignificantly higher percentage (83.9 versus

67.3%; X2 = 7.20; P < 0.01) of rotavirus infec-tions in these patients had occurred by the endof the first year of life.

DISCUSSIONThis paper summarizes data from what may

be the longest continuous study in the UnitedStates for recently described enteritis viruses. Inaddition to reporting patterns of infection byyear, season, age, sex, and race/socioeconomicstatus, we have attempted to find epidemiologi-cal evidence of differences in exposure to theseviruses in identifiable subpopulations of pediat-ric study subjects. For the purposes of thispaper, no attempt has been made to documentadditional infections demonstrable by recoveryof viral and bacterial pathogens or by serumantibody response.

Rotaviruses, adenoviruses, and -27-nm vi-ruses apparently are causally associated withgastroenteritis in this locale, since each of thesegroups of viruses has been detected by EM or

IEM significantly more often in fecal specimensfrom patients with enteritis than from controlsubjects (5). Rotaviruses in our study populationappear primarily to belong to ELISA subgroup 2(5), usually have fast-migrating RNA genes 10and 11 on electrophoresis (W. J. Rodriguez,H. W. Kim, C. D. Brandt, M. K. Gardner, andR. H. Parrott, J. Infect. Dis., in press), and tendto be type 1 (Wa-like) by neutralization test (10,

26; C. D. Brandt, B. C. Jeffries, H. W. Kim, J. 0.Arrobio, E. P. Stallings, W. J. Rodriguez, andR. H. Parrott, Pediatr. Res. 17:266A, 1983).Adenoviruses that were visualized in stools of

our diarrhea patients usually did not grow readi-ly in conventional cell cultures (human embry-onic kidney, HEp-2, or monkey kidney), al-though most have grown serially with theproduction of cytopathic effects when inoculat-ed into 293 cells (3, 5, 25). Adenoviruses thatgrow readily in conventional cell cultures tend tobe associated with respiratory disease ratherthan diarrhea, and they may be shed in stools formonths or even years after infection 1, 4, 7, 9,11). In stools, respiratory adenoviruses typicallyare present in too low a concentration to bedetected by our EM or IEM techniques. Diar-rhea-associated adenoviruses from our studysubjects, analyzed by restriction endonucleasecleavage and agarose gel electrophoresis, appar-ently are primarily from electrophoretic sub-group G (28; H. E. Takiff and S. E. Straus,Abstr. 1982 Tumor Virus Meeting on SV40,Polyoma, and Adenoviruses, Cold Spring Har-bor, N.Y., p. 60; H. Takiff, S. Straus, R. Yol-

TABLE 3. Rotavirus infections in gastroenteritisinpatients during November through June, by race

No. tested No. (%) infectedMonth

Black Nonblack Black Nonblack

November 49 20 8 (16.3) 2 (10.0)December 72 25 23 (31.9) 9 (36.0)January 181 69 123 (68.0) 45 (65.2)February 144 75 70 (48.6) 57 (76.0)March 88 54 37 (42.0) 28 (51.9)April 70 30 12 (17.1) 13 (43.3)May 54 17 6 (11.1) 4 (23.5)June 63 12 0 (0) 1 (8.3)Total 721 302 279 (38.7) 159 (52.6)

J. CLIN. MICROBIOL.74 BRANDT ET AL.

on Septem

ber 8, 2020 by guesthttp://jcm

.asm.org/

Dow

nloaded from

PEDIATRIC VIRAL GASTROENTERITIS 75

TABLE 4. Virus infections in gastroenteritis inpatients, by patient age

Age No. No. (%) with indicated infection(mo) tested Rotavirus Adenovirus -27-nm virus Total'

0-3 406 64 (15.8) 16 (3.9) 4 (1.0) 82 (20.2)4-6 203 67 (33.0) 19 (9.4) 4 (2.0) 88 (43.3)7-9 173 97 (56.1) 10 (5.8) 7 (4.0) 110 (63.6)10-12 136 76 (55.9) 6 (4.4) 2 (1.5) 83 (61.0)13-18 109 61 (56.0) 10 (9.2) 2 (1.8) 72 (66.1)19-24 65 32 (49.2) 1 (1.5) 1 (1.5) 33 (50.8)25-36 64 24 (37.5) 3 (4.7) 1 (1.6) 28 (43.8)37-48 33 8 (24.2) 0 (0) 1 (3.0) 9 (27.3)249 90 9 (10.0) 2 (2.2) 1 (1.1) 12 (13.3)

a See footnote b of Table 1.

ken, and C. Brandt, Abstr. Annu. Meet. Am.Soc. Microbiol. 1982, S73, p. 247), and most thathave been tested have been neutralized by anantiserum (kindly supplied by S. Straus) thatwas prepared against one of our enteral adeno-viruses (25).Our -27-nm viruses are not well character-

ized. On the basis of electron micrographicappearance, some astroviruses, caliciviruses,and minirotaviruses are included in this group,but most -27-nm viruses have been round parti-cles with no obvious morphology. Fecal prepa-rations containing our -27-nm viruses rarelyhave produced cytopathic effects when inoculat-ed into monkey kidney, HEp-2, or human em-bryonic kidney cells, and we have recoveredonly an occasional enterovirus (or nonvisualizedadenovirus) after such inoculation. Approxi-mately 20 of our -27-nm viruses from a varietyof inpatients and outpatients with gastroenteritishave been tested and found not to be Norwalk-like (H. Greenberg et al., unpublished data). Inaddition, we have tested 23 fecal preparationscontaining -27-nm viruses in IEM tests withpre- and postimmunization rabbit serum pre-pared against a human astrovirus (sera and con-

trol virus kindly supplied by T. W. Lee, Oxford,England) (17). Only the control virus from a

human volunteer who had been challenged withastrovirus and one (4.3%) of our test specimenswere positive for astrovirus.

In the present study, infections that were seenin January and February and among nonblackinpatients who were 13 through 18 months of ageespecially attest to the high frequencies of enter-ic viral infections that can occur and to thesensitivity of our EM and rotavirus ELISAtechniques.

All inpatients in this study who were foundpositive by ELISA also were found (after someretesting) to be rotavirus positive by EM or

IEM. This finding especially attests to the speci-ficity of our present rotavirus ELISA technique.False-positivity of a previous ELISA test led inthe past to our reporting two rotavirus infectionsin July of 1976 (5). These infections could not beconfirmed by EM, IEM, or later by an improvedELISA with higher specificity (3). However, itshould be noted that EM-positive rotavirus in-fections did in fact occur in July 1982.Three patients in this study (and two other

patients in related work involving an additional191 virus-positive children and adults) havebeen found to have particles in their stoolswhich morphologically were rotaviruses, butwhich repeatedly failed to show rotavirus posi-

TABLE 5. Virus infections in gastroenteritis inpatients, by age and race

No. (%) with indicated infectionAge No. tested(MO) Rotavirus Any virus'

Black Nonblack Black Nonblack Black Nonblack

0-3 331 75 57 (17.2) 7 (9.3) 70 (21.1) 12 (16.0)4-6 159 44 56 (35.2) 11 (25.0) 73 (45.9) 15 (34.1)7-9 120 53 63 (52.5) 34 (64.2) 73 (60.8) 37 (69.8)10-12 97 39 50 (51.5) 26 (66.7) 55 (56.7) 28 (71.8)13-18 64 45 24 (37.5) 37 (82.2) 31 (48.4) 41 (91.1)19-24 38 27 16 (42.1) 16 (59.3) 16 (42.1) 17 (63.0)25-36 31 33 7 (22.6) 17 (51.5) 8 (25.8) 20 (60.6)37-48 20 13 2 (10.0) 6 (46.2) 2 (10.0) 7 (53.8).49 57 33 4 (7.0) 5 (15.2) 6 (10.5) 6 (18.2)

Total 917 362 279 (30.4) 159 (43.9) 334 (36.4) 183 (50.6)

a Rotavirus, adenovirus, -27-nm virus, or a combination.

VOL. 18, 1983

on Septem

ber 8, 2020 by guesthttp://jcm

.asm.org/

Dow

nloaded from

TABLE 6. Virus infections among gastroenteritis inpatients, by sex and raceRotavirus Adenovirus -27-nm virus

Study group te%No. Median Median MedianStudygroup tested No. % No. % No. %positive Positive age positive Positive age positive Positive age(MO) Po(MO) poiie(MO)

Male 726 264 36.4 9 37 5.1 7 18 2.5 9Female 553 174 31.5 9 30 5.4 5 5 0.9 9

Black 917 279 30.4 7 47 5.1 5 15 1.6 7Nonblack 362 159 43.9 13 20 5.5 10.5 8 2.2 9

Black male 512 169 33.0 8 24 4.7 6.5 12 2.3 8Nonblack male 214 95 44.4 12 13 6.1 10 6 2.8 8.5

Black female 405 110 27.2 7 23 5.7 5 3 0.7 6Nonblack female 148 64 43.2 15 7 4.7 11 2 1.4 17

Total 1,279 438 34.2 9 67 5.2 6 23 1.8 9

tivity by ELISA. Thus 5 (0.7%) of 721 presump-tive rotavirus infections that we have studiedappear to be caused by uncommon rotavirusesor rotavirus-like agents similar to one recentlyreported from Australia (22). Two such agentswere found in February 1981, the remainingthree were found in February and March 1982,and all occurred in gastroenteritis patients whowere less than 9 months of age.The reasons for a higher percentage of rota-

virus infections among study patients in theeven-numbered as compared with the odd-num-bered calendar years are not clear at present.Unusually cold, dry, warm, or wet weather mayhave influenced rotavirus infections in any oneyear, but such conditions do not occur cyclicallyin this locale in even- or odd-numbered calendaryears (2, 24). Findings relating to the electro-pherotype and neutralizing serotype of viruseswhich infected study subjects in different calen-

dar years may ultimately shed light on thisquestion.Our data which compare infection in blacks

and nonblacks should be interpreted with cau-tion, as there may be important differences inthe composition of these study populations. Thismedical center provides a larger proportion of allhospital care for District of Columbia childrenthan for suburban children. The latter tend to bereferred for tertiary care or severe illness. Thuswe probably studied a wider spectrum of diar-rheal disease among inpatients from the Districtof Columbia (predominantly black) than fromthe suburbs (majority nonblack). If rotavirusinfection causes a relatively high frequency ofsevere illness, differences in the sampled popu-lations could explain why a higher percentage ofnonblacks than blacks were found to have rota-virus infection.

Major differences in the patterns of infection

TABLE 7. Rotavirus infections in gastroenteritis inpatients during periods of high versus low prevalence ofinfection, by age and race

Total Median age (mo) No. (%) of total rotavirus infections found in infantsStudy Virus rotavirus of those with of indicated agegroup prevalence infections rotavirus -3 mo -6 mo -9 mo -12 moBlack Higha 230 7 49 (21.3) 97 (42.2) 152 (66.1) 193 (83.9)b

LowC 49 9.5 8 (16.3) 16 (32.7) 24 (49.0) 33 (67.3)b

Nonblack High 130 12 7 (5.4) 15 (11.5) 43 (33.1) 65 (50.0)Low 29 13 0 (0) 3 (10.3) 9 (31.0) 13 (44.8)

Totald High 360 9 56 (15.6) 112 (31.1) 195 (54.2) 258 (71.7)eLow 78 10 8 (10.3) 19 (24.4) 33 (42.3) 46 (59.0)e

a January through March.bx2 = 7.20, P < 0.01.c November, December, and April through June.d Total includes infants and young children.eX = 4.86, P < 0.05.

J. CLIN. MICROBIOL.76 BRANDT ET AL.

on Septem

ber 8, 2020 by guesthttp://jcm

.asm.org/

Dow

nloaded from

PEDIATRIC VIRAL GASTROENTERITIS 77

in our black and nonblack patients with respectto season and age probably cannot be explainedas having resulted merely from a sampling of"less ill" versus "more ill" patients. However,because of possible differences in the spectrumof illness in our study populations, we have notattempted to calculate statistical significance forseveral findings related to race which mightotherwise have been compared.A variety of evidence suggests that our black

study subjects as a group were more exposed toenteric infections than were their nonblackcounterparts. For example, acute enteric illnessand infections by all of the enteric viruses stud-ied tended to occur earlier in life among inpa-tients who were black. Also, the seasonal waveof rotavirus infections tended to appear in andthen progress more rapidly through the blackthan the nonblack study subjects.The median age of groups of infected individ-

uals may provide a useful index of relativeexposure to enteric infection, with a lower medi-an age indicating greater exposure. Several ob-servations support or are consistent with thishypothesis. For example, with respect to allenteric viral infections studied, the median ageof infected black children was lower than that ofinfected nonblack children. In addition, we havepreviously shown a lower median age amongvirus-infected residents as compared to nonresi-dents of the District of Columbia, and amongMedicaid recipients (poorer individuals) as com-pared with nonrecipients of Medicaid (5). Fur-thermore, we found in the present study that themedian age of rotavirus-infected inpatients waslower in months when rotaviruses were mostactive (greater exposure) as compared with thatin months when they were minimally active(lesser exposure).

In a previous report (2) we observed a fall inmedian age of rotavirus-infected children as wellas a greater number and a higher frequency ofhospitalizations for rotavirus gastroenteritis af-ter cold or dry weather, which suggests a weath-er-related increase in exposure to rotavirus in-fection. Low indoor relative humidity may be aparticularly important factor in the latter phe-nomenon, since very young infants were espe-cially prone to show weather-related effects de-spite spending most of their time indoors.Low outdoor humidity has been related to

increased rotaviruses disease in Nigeria (21), butnot in Japan (16). However, in Japan a largerproportion of rotavirus-positive patients were<12 months of age in December through Febru-ary than in the other months taken as a group(16); this finding could be consistent with anindoor relative humidity effect.A considerable effect of factors related to cold

weather and low indoor humidity is also suggest-ed by the clocklike precision of the annual wave

of rotavirus infection in Washington, D.C.,which has been more regular and predictablethan that of any pediatric pathogen which thislaboratory has investigated, including respira-tory syncytial virus (14, 20), influenza A and Bviruses (15), the respiratory adenoviruses (1),parainfluenza viruses (6; C. D. Brandt, H. W.Kim, R. M. Chanock, and R. H. Parrott, Pe-diatr. Res. 8:148, 1974), the traditional enterovi-ruses (18), and Mycoplasma pneumoniae.From our various observations, one might

predict that the presence in combination offamilies with infants and young children, pover-ty, poor sanitation, temperate climate, dry con-ditions, and the onset of cool weather could leadto rotavirus outbreaks that would begin usuallyearly in the epidemic season, build explosively,decline rapidly (as the number of susceptiblechildren decreased), and especially involve in-fants. Such in fact appears to be the case in twoArizona Indian populations that have recentlybeen described. Apache Indians living on desertreservations apparently experience brief sharpoutbreaks of rotavirus gastroenteritis which es-pecially involve young infants (8) and whichoccur in October and November, soon after theonset of cool weather (8; Santosham et al., 22ndICAAC, abstr. no. 897).

LITERATURE CITED

1. Brandt, C. D., H. W. Kim, B. C. Jeffries, G. Pyles, E. E.Christmas, J. L. Reid, R. M. Chanock, and R. H. Parrott.1972. Infections in 18,000 infants and young children in acontrolled study of respiratory tract disease. II. Varia-tions in adenovirus infections by year and season. Am. J.Epidemiol. 95:218-227.

2. Brandt, C. D., H. W. Kim, W. J. Rodriguez, J. 0. Arro-bio, B. C. Jeffries, and R. H. Parrott. 1982. Rotavirusgastroenteritis and weather. J. Clin. Microbiol. 16:478-482.

3. Brandt, C. D., H. W. Kim, W. J. Rodriguez, L. Thomas,R. H. Yolken, J. 0. Arrobio, A. Z. Kapikian, R. H. Par-rott, and R. M. Chanock. 1981. Comparison of directelectron microscopy, immune electron microscopy, androtavirus enzyme-linked immunosorbent assay for detec-tion of gastroenteritis viruses in children. J. Clin. Microbi-ol. 13:976-981.

4. Brandt, C. D., H. W. Kim, A. J. Vargosko, B. C. Jeffries,J. 0. Arrobio, B. Rindge, R. H. Parrott, and R. M. Chan-ock. 1969. Infections in 18,000 infants and children in acontrolled study of respiratory tract disease. I. Adenovi-rus pathogenicity in relation to serologic type and illnesssyndrome. Am. J. Epidemiol. 90:484-500.

5. Brandt, C. D., H. W. Kim, R. H. Yolken, A. Z. Kapikian,J. 0. Arrobio, W. J. Rodriguez, R. G. Wyatt, R. M.Chanock, and R. H. Parrott. 1979. Comparative epidemi-ology of two rotavirus serotypes and other viral agentsassociated with pediatric gastroenteritis. Am. J. Epidemi-ol. 110:243-254.

6. Brandt, C. D., R. H. Parrott, J. R. Patrick, H. W. Kim,J. 0. Arrobio, R. Chandra, B. C. Jeffries, and R. M.Chanock. 1975. The sudden infant death syndrome andviral respiratory disease in metropolitan Washington,D.C. Clin. Proc. Child. Hosp. Natl. Med. Ctr. 31:202-213.

7. Brandt, C. D., F. W. Wassermann, and J. P. Fox. 1966.The Virus Watch Program IV. Recovery and comparisonof two serological varieties of adenovirus type 5. Proc.Soc. Exptl. Biol. Med. 123:513-518.

VOL. 18, 1983

on Septem

ber 8, 2020 by guesthttp://jcm

.asm.org/

Dow

nloaded from

78 BRANDT ET AL.

8. Engleberg, N. C., E. N. Holburt, T. J. Barrett, G. W.Garry, Jr., M. H. Trujillo, R. A. Feldman, and J. M.Hughes. 1982. Epidemiology of diarrhea due to rotaviruson an Indian reservation: risk factors in the home environ-ment. J. Infect. Dis. 145:894-898.

9. Fox, J. P., C. D. Brandt, F. E. Wassermann, C. E. Hall, I.Spigland, D. M. Deutsch, A. Kogon, and L. R. Elveback.1969. The Virus Watch Program: a continuing surveil-lance of viral infections in metropolitan New York fam-ilies. VI. Observations of adenovirus infections: virusexcretion patterns, antibody response, efficiency of sur-veillance, patterns of infection, and relation to illness.Am. J. Epidemiol. 89:25-50.

10. Greenberg, H. B., R. G. Wyatt, A. Z. Kapikian, A. R.Kalika, J. Flores, and R. Jones. 1982. Rescue and serotyp-ic characterization of noncultivable human rotavirus bygene reassortment. Infect. Immun. 37:104-109.

11. Hall, C. E., C. D. Brandt, T. E. Frothingham, I. Spigland,M. K. Cooney, and J. P. Fox. 1971. The Virus WatchProgram: a continuing surveillance of viral infections inmetropolitan New York families. IX. A comparison ofinfections with several respiratory pathogens in NewYork and New Orleans families. Am. J. Epidemiol.94:367-385.

12. Kapikian, A. Z., H. W. Kim, R. G. Wyatt, W. L. Cline,J. 0. Arrobio, C. D. Brandt, W. J. Rodriguez, D. A.Sack, R. M. Chanock, and R. H. Parrott. 1976. Humanreovirus-like (HRVL) agent as the major pathogen associ-ated with "winter" gastroenteritis-etiologic, epidemio-logic studies in infants, young children and their contacts.New Engi. J. Med. 294:965-972.

13. Kapikian, A. Z., R. H. Yolken, H. B. Greenberg, R. G.Wyatt, A. R. Kalika, R. M. Chanock, and H. W. Kim.1979. Gastroenteritis viruses, p. 927-995. In E. H. Len-nette and N. J. Schmidt (ed.), Diagnostic procedures forviral, rickettsial and chlamydial infections, vol. 5. Ameri-can Public Health Association, Inc., Washington, D.C.

14. Kim, H. W., J. 0. Arroblo, C. D. Brandt, B. C. Jeffries,G. Pyles, J. L. Reid, R. M. Chanock, and R. H. Parrott.1973. Epidemiology of respiratory syncytial virus infec-tion in Washington, D.C. I. Importance of the virus indifferent respiratory tract disease syndromes and tempo-ral distribution of infection. Am. J. Epidemiol. 98:216-225.

15. Kim, H. W., C. D. Brandt, J. 0. Arroblo, B. Murphy,R. M. Chanock, and R. H. Parrott. 1979. Influenza A andB virus infection in infants and young children during theyears 1957-1976. Am. J. Epidemiol. 109:464-479.

16. Konno, T., H. Suzuki, N. Katsushima, A. Imai, F. Tazawa,T. Kutsuzawa, S. Kitaoka, M. Sakamoto, N. Yazaki, and

N. Ishida. 1983. Influence of temperature and relativehumidity on rotavirus infection in Japan. J. Infect. Dis.147:125-128.

17. Kurtz, J. B., T. W. Lee, J. W. Craig, and S. E. Reed.1979. Astrovirus infection in volunteers. J. Med. Virol.3:221-230.

18. Marrier, R., W. Rodriguez, R. J. Chloupek, C. D. Brandt,H. W. Kim, R. S. Baltimore, C. L. Parker, and M. S.Artenstein. 1975. Coxsackie virus B5 infection and asepticmeningitis in neonates and young children. Am. J. Dis.Child. 129:321-325.

19. Middleton, P. J., M. T. Szymanski, and M. Petric. 1977.Viruses associated with acute gastroenteritis in youngchildren. Am. J. Dis. Child. 131:733-737.

20. Parrott, R. H., H. W. Kim, J. 0. Arroblo, D. S. Hodes,B. R. Murphy, C. D. Brandt, E. Camargo, and R. M.Chanock. 1973. Epidemiology of respiratory syncytialvirus infection in Washington, D.C. II. Infection anddisease with respect to age, immunologic status, race andsex. Am. J. Epidemiol. 98:289-300.

21. Paul, M. O., and E. A. Erinle. 1982. Influence of humidityon rotavirus prevalence among Nigerian infants andyoung children with gastroenteritis. J. Clin. Microbiol.15:212-215.

22. Rodger, S. M., R. F. Bishop, and I. H. Holmes. 1982.Detection of a rotavirus-like agent associated with diar-rhea in an infant. J. Clin. Microbiol. 16:724-726.

23. Rodriguez, W. J., H. W. Kim, C. D. Brandt, B. Bise,A. Z. Kapikian, R. M. Chanock, G. Curlin, and R. H.Parrott. 1980. Rotavirus gastroenteritis in the Washing-ton, D.C. area. Am. J. Dis. Child. 134:777-779.

24. Ruffner, J. A., and F. E. Blair. 1977. The weather alma-nac. Avon Books, New York.

25. Takiff, H. E., S. E. Straus, and C. F. Garon. 1981. Propa-gation and in vitro studies of previously non-cultivableenteral adenoviruses in 293 cells. Lancet ii:832-834.

26. Thouless, M. E., G. M. Beards, and T. H. Flewett. 1982.Serotyping and subgrouping of rotavirus strains by theELISA Test. Arch. Virol. 73:219-230.

27. Tyrrell, D. A. J., and A. Z. Kapikian (ed.). 1982. Virusinfections of the gastrointestinal tract. Marcel Dekker,Inc., New York.

28. Wadell, G., M. Hammarskjold, G. Winberg, T. M. Var-sanyl, and G. Sundell. 1980. Genetic variability of adeno-viruses. Ann. N.Y. Acad. Sci. 354:15-42.

29. Yolken, R. H., F. Lawrence, F. Leister, H. E. Takiff, andS. E. Straus. 1982. Gastroenteritis associated with enterictype adenovirus in hospitalized infants. J. Pediatr. 101:21-26.

J. CLIN. MICROBIOL.

on Septem

ber 8, 2020 by guesthttp://jcm

.asm.org/

Dow

nloaded from