JOURNAL OF CLINICAL MICROBIOLOGY, May 1990, p. 1033-1038

Vol. 28, No. 5

0095-1137/90/051033-06$02.00/0 Copyright 0) 1990, American Society for Microbiology

Distinct Populations of Rotaviruses Circulating Older Infants

among

Neonates and

JOHN S. L. TAM,l* BO JIAN ZHENG,' SIMON K. LO,1 CHAP YUNG YEUNG,2 MONA LO,3 AND MUN HON NG' Departments of Microbiologyl and Paediatrics,2 University of Hong Kong, and Kwun Tong Community Health Project, United Christian Medical Services,3 Kwun Tong, Hong Kong Received 21 November 1989/Accepted 5 February 1990

We obtained three stool specimens from each of 371 neonates. Two specimens were obtained between days 1 and 3 after birth, while they were in the hospital, and one specimen was obtained between days 6 and 14 after birth, after they had been discharged from the hospital. Seventy neonates excreted human rotavirus (HRV) while they were in the hospital, and the incidence rate for the cohort was 0.094 episodes per infant day. The incidence rate of community-acquired neonatal infections was markedly reduced to 0.022 episodes per infant day, with eight additional episodes of infection being detected after the infants were discharged from the hospital. Nevertheless, this was higher than the incidence of community-acquired HRV infection of 0.0037 episodes per infant day previously estimated by serology for the same cohort during the subsequent 2 years of infancy. None of the 78 episodes of neonatal HRV infection was accompanied by diarrhea. There were at least 44 distinct electropherotypes of HRV circulating among older infants in the community during the study period, and they comprised at least four different serotypes. Despite the genetic and antigenic diversity of the prevalent HRV isolates, only five electropherotypes with either serotype 2 or 4 specificity were isolated from the neonates, while serotype 1 and 3 viruses were not detected. Two of these electropherotypes, including one which was isolated from 57 of the 78 infants with episodes of infection, were isolated exclusively from the neonates. The other three electropherotypes were also isolated from the older infants; one was a major electropherotype and two were minor electropherotypes which were prevalent among the older infants. These results suggest that distinct populations of HRV cocirculate among neonates and older infants.

Neonates frequently excrete human rotavirus (HRV) in their stools. The clinical and epidemiological features of the infection are different from that which occurs in older infants. Neonatal HRV infections usually are transient and do not cause diarrhea (3, 5, 9, 11), although severe diarrhea (15) and enterocolitis have been reported (12). Unlike the diarrhea caused by HRV in older infants, which has a marked seasonal distribution, neonatal infections occur throughout the year. More recently, it was found that neonates and older infants may be infected with distinct populations of HRV (1), and this may explain, in part, the different features of the infections of the two groups. Earlier findings suggested that neonatal HRV infection may confer protection against the subsequent development of diarrhea caused by the virus (2). Since the strains of the virus found in neonates appear to be less virulent than those that are prevalent among the older infants, it is thought that they may serve as a candidate vaccine against one of the most common causes of diarrhea during infancy. Most previous studies of neonatal infection with HRV were conducted in hospitals and institutions. Since HRV infections spread efficiently in hospitals (13, 16), the results may overestimate the extent of occurrence of the infection. We conducted concurrently a longitudinal, communitybased study and a horizontal, hospital-based study of infantile diarrhea between 1983 and 1985. Hospital-acquired and community-acquired HRV infections of neonates were directly compared by obtaining three stool specimens from each of 371 neonates that were recruited into the prospective study. Two specimens were obtained during the first 3 days of life, while the neonates were in the hospital, and one *

specimen was obtained between 6 and 14 days after birth, after they were discharged from the hospital. The viruses that were isolated were compared by electropherotyping. Their serotype specificities were determined by dot hybridization (17). The results for those isolates obtained from the hospitalized and ambulatory patients with diarrhea caused by HRV were compared. We show that distinct populations of HRV are prevalent among the neonates and older infants. (This work was conducted by B.J.Z. and J.S.L.T. in partial fulfillment of the Ph.D. requirements of the University of Hong Kong.) MATERIALS AND METHODS Recruitment of cohort. We recruited 371 infants at birth and followed them for 2 years for the development of diarrhea. To compensate for seasonal changes in the patterns of diarrhea, the recruitment was conducted over 13 months, between November 1983 and December 1984. All the infants were born in the United Christian Hospital and resided in a district of Hong Kong on the Kowloon Penisular (Kwun Tong), where the hospital is also located. The infants were from low- to lower-middle-income families living in crowded conditions in tenements or temporary housing. Their parents were young, and many of them were not educated beyond the primary school level. Hospitalized and ambulatory controls with diarrhea. To ensure that enrollment in this study did not bias the results, we also conducted, in parallel, a horizontal communitybased study and a hospital-based study. In the communitybased study, we recruited 66 patients with diarrhea caused by HRV who were less than 2 years of age, who were from the same community in Kwun Tong, and who were not enrolled in the prospective study. For the hospital-based

Corresponding author. 1033

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J. CLIN. MICROBIOL.

TAM ET AL.

study, we recruited 431 patients with diarrhea caused by HRV who were less than 5 years of age and who were admitted to Queen Mary Hospital on Hong Kong Island. Neonatal HRV infection. Two stool specimens were obtained between days 1 and 3 after birth but before discharge from the hospital, and one specimen was obtained between days 6 and 14 after birth, when the infants were visited at home by a community nurse. The specimens were tested for HRV by an enzyme-linked immunosorbent assay and by electropherotyping, as described previously (13). The serotype specificities of the isolates were determined by RNA dot hybridization by using cDNA probes derived from segment 9 of the rotavirus genome, as described previously (17). Follow-up study. Infants were examined monthly by a physician at one of the three community clinics located in their district. During the monthly visits, body weight and length and head circumference were measured, and feeding habits and the occurrence of diarrhea were recorded. The infants were assessed for psychomotor development every 4 months. Serum specimens also were obtained every 4 months. Diarrhea monitoring. For the purposes of this study, diarrhea was defined as the passing of four or more loose, watery stools in a single day, according to the Guideline for the Trainers of Community Health Workers on the Treatment and Prevention of Acute Diarrhoea (World Health Organization/CDD/SER/80.1). Mothers were advised on the clinical signs of diarrhea and were asked to inform the community health clinics within 24 h of its onset in person or by telephone. The infants were examined in the clinics or at home by the community nurse. They were assessed for dehydration and weight loss and were given immediate medical attention as appropriate. Repeated stool specimens were obtained for investigation. Microbiological investigation. All serum and stool specimens were transported under refrigeration within 2 days of collection and investigated at the Queen Mary Hospital. The stool specimens were investigated for the presence of salmonella, campylobacter, shigellas, enterotoxigenic and enteropathogenic Escherichia coli, Aeromonas hydrophila, Vibrio species, and HRV. Control specimens were routinely included with the test specimens to ensure that the organisms remained viable during storage and transport. Healthy controls. Stool specimens were obtained from some of the infants enrolled in the prospective study who did not have signs of diarrhea within 2 weeks of a monthly visit to the clinics. The specimens were investigated for healthy carriage of the enteric pathogens mentioned above. RESULTS Between November 1983 and December 1984, we recruited 371 infants at birth (Fig. 1) and followed them for the development of diarrheal diseases until they were 2 years of age. All the infants were born in the United Christian Hospital and resided in a suburb (Kwun Tong) on the east side of the Kowloon Penisula. To study neonatal HRV infection, we obtained two stool specimens from each of the neonates between days 1 and 3 after birth, while they were in the hospital, and one additional specimen was obtained between days 6 and 14 after birth, when the neonates were visited at home by a community nurse. HRV was isolated from 70 neonates while they were in the hospital, and an additional 8 specimens obtained from infants after they were discharged were positive; this included one specimen from a

Infants born

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40 b_

c 30

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20

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=

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i

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Community acquired

CL e

.

Hospital acquired

2

0

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HRV diarrhea

Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 1- ag.-I-

1984

FIG. 1. Seasonal occurrence of HRV infections of neonates and older infants. A total of 371 newborn infants were recruited between November 1983 and December 1984 (infants born). Two stool specimens were obtained between days 1 and 3 after birth, while they were in the hospital, and 70 of those specimens were positive for HRV (hospital acquired). An additional stool specimen was obtained between days 6 and 14 after birth, after the infants were discharged from the hospital, and eight of these specimens were positive for HRV (community acquired). The seasonal occurrence of HRV diarrhea in ambulatory older infants in the same community (HRV diarrhea) was also examined.

neonate who was infected with another electropherotype of HRV when she was in the hospital. The difference in the frequencies of isolation was significant (P < 0.01). None of these episodes of infection was associated with diarrhea. Figure 1 shows that infections occurred throughout the year. This was in contrast to the marked seasonal distribution of diarrhea caused by HRV that occurred in older infants residing in the same community during the same period. As summarized in Table 1, the incidence rates of HRV neonatal infections were 0.0943 [70/(371 x 2)] and 0.0216 (8/371) episodes per infant day while the infants were in the hospital and after the infants were discharged, respectively. We did not monitor for asymptomatic HRV infections among older infants interned in the hospital. Nevertheless, we obtained stool specimens from 341 infants without diarrhea who visited the community clinics in the same suburb TABLE 1. Incidence rates of HRV infection during the neonatal period and early infancy HRV infection acquired from:

Hospital Community Community

ge

No. of episodes/ infant day (10-O)

1-3 days 6-14 days .. .1

5 6

1*w , . _ >s

ROTAVIRUSES AMONG NEONATES AND OLDER INFANTS

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S2-9 11 2 3 4 5 6

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s

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FIG. 2. Electropherotypes of HRV isolated from neonates. Five distinct electropherotypes were isolated from 74 neonates. The electropherotype designations were as described by Tam et al. (13). They were compared with electropherotypes of the prototype strains Wa and S2. The locations of segments 1 to 11 of the rotavirus genome are as indicated.

between November 1983 and December 1985. None of the control infants excreted HRV, however. As compared with the excretion of HRV by the neonates between days 6 and 14 after birth, after they were discharged from the hospital, it was found that HRV infection indeed occurred significantly more frequently among the neonates than it did among the older infants in the same community. Of 371 neonates tested, 8 excreted HRV isolates in their stool specimens, whereas none of the controls was found to excrete HRV (x2, 7.437; P < 0.01). This contention was supported by the results of a prospective serological study of the same cohort (18), showing that HRV infection occurred constantly throughout the 2 years of the study period at an incidence rate of 0.0037 episodes per infant day, with the majority of infants being asymptomatic (Table 1). Thus, HRV infection seemed to become less frequent after the neonatal period. Stool specimens from 74 of the neonates were adequate for electropherotyping (Fig. 2), and 62 of them were also adequate for serotyping by dot hybridization by using cDNA derived from segment 9 of the genomes of serotype 1 to 4 prototype viruses (Fig. 3) as probes. These specimens yielded five distinct electropherotypes, two of which were "short" electropherotypes (IA1 or IA11) that are characteristic of subgroup 1 rotavirus. These isolates hybridized specifically with cDNA derived from the serotype 2 virus. The other isolates (IIA2, IIA6, and IIA20) had "long" electropherotypes. IIA2 isolates were not adequate for dot hybridization. Isolates with the other two electropherotypes hybridized specifically with the probe derived from the serotype 4 virus. The results obtained with the neonatal isolates were compared with those obtained similarly in Queen Mary Hospital, which is located on Hong Kong Island, from 418

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FIG. 3. Determination of the serotype specificities of neonatal HRV isolates by dot hybridization. The cDNA probes used were derived from total RNA from serotype 1 to 4 viruses (total) or segment 9 of the genome of the prototype rotavirus strains Wa (Wa-9), S2 (S2-9), YO (YO-9), and Hochi (Hochi-9). The RNAs of the neonatal HRV isolates, strains IA1 and IA11, were spotted onto column 1 and the RNA of strain IIA6 was spotted onto column 2, rows A to H, in panel A. RNAs of strain IIA20 were spotted onto columns 1 to 5, rows A to H, and column 6, rows A to D, in panel B. The results were compared with those obtained concurrently with the prototype viruses in columns 3, row A (Wa), row B (S2), row C (Yo), and row D (Hochi), as described above for panel A, or in columns 6, row D (Wa), row E (S2), row F (Yo), and row G (Hochi), as described above for panel B.

infants with diarrhea caused by HRV and 66 ambulatory patients with diarrhea caused by HRV who visited the community clinics at Kwun Tong during the same period (Table 2). The virus population that was prevalent in these older infants was genetically and antigenically diverse, much more so than those isolated from the neonates. A total of 44 distinct electropherotypes were detected among the hospitalized patients, and 19 distinct electropherotypes were detected among the ambulatory patients. There were 6 distinct short electropherotypes, all of which were found to hybridize specifically with the cDNA probe derived from the serotype 2 virus. The other isolates had long electropherotypes, most of which hybridized with the cDNA probe from serotype 1, 3, or 4 virus. A small number of these isolates hybridized simultaneously with serotype 1 and 4 probes, but we were not able to determine whether these isolates had a distinct serotype specificity. Since all isolates with the same electropherotypes also consistently gave the same results by dot hybridization, it was possible to correlate the results

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J. CLIN. MICROBIOL.

TAM ET AL.

TABLE 2. Distribution of electropherotypes and serotypes of HRV isolates among neonates and older infants ertes

1

Electro-

pherotypea RIA1 IIA7

No. of observed (no. of expected) cases of infection seen in: Hospitalized Community- Neonates Total infants based infants

Others

13 (16) 25 (26) 15

8 (2) 10 (4) 4

lAi IA5 lA11 Others

4 (7) 49 (43) 0 (1.5) 9

2 (1) 9 (7)

3

1ID3 Others

4

IIA6 IIA20b LICi Others

2

NT

IIA2 Others

Total

0 (3) 0 (5) 0

21 35 19

2

3 (1) 0 (8) 2 (0.3) 0

9 58 2 il

21 (17) 16

2 (3) 9

0 (3) 0

23 25

38 (36) 0 (42) 148 (117) 34

1 (6) 0 (7) 9 (18) 3

10 (7) 57 (8)

49 57

5 (6)

1 (1) 6

41

418

0 (0.2)

66

0 (22) 0

157 37

2 (1) 4

8 51

78

562

a The other isolates were minor electropherotypes isolated from older infants only; they included 8 serotype 1 electropherotypes (IIA9, IIA10, IIA12, IIB1, IIB3, IIC4, IIE1, and IIE4); 4 serotype 2 electropherotypes (IA2, IA3, IA4, and IA6); 4 serotype 3 electropherotypes (IIA3, IIC2, IID2, and IID4); 10 serotype 4 electropherotypes (IIA4, IIA8, IIA11, IIA13, IIA14, IIB4, IIB8, IIC3, IIC5, and IIE2), and 10 electropherotypes with unknown serotypes (NT) (IIA7, IIB5, IIB7, IIA5, IIB2, IIB6, IIB9, IIC6, IIE3, and IID1). Four neonatal isolates were inadequate for serotyping or electropherotyping. b Strains of HRV were isolated from neonates only.

obtained by these methods, as shown in Table 2. The results indicate that at least four different serotypes of HRV were cocirculating among the older infants in this community during the study period, with the serotype 4 virus being the most prevalent, whereas only serotype 2 and 4 viruses were isolated from the neonates during the same period. Table 2 also shows that all the major electropherotypes were simultaneously isolated from older infants in Kwun Tong on the Kowloon Penisular and from older infants on Hong Kong Island. Although the distribution of these and other electropherotypes between the two groups of patients was different from what might be expected for the three groups of study subjects as a whole, the results nevertheless suggest that these viruses circulate freely in Kwun Tong. This was in marked contrast to the results obtained with the neonates; except for electropherotype IIA6, none of the other major electropherotypes circulating among the older infants (IIA1, IIA7, IAS, IID3, and IIC1) was isolated from the neonates. Notably, serotype 1 and 3 viruses were not isolated from the neonates. Apart from electropherotype IIA6, two other minor electropherotypes (IA1 and IIA2) were also simultaneously isolated from the neonates and older infants. The remaining two electropherotypes (IA11 and IIA20) were isolated exclusively from the neonates. These results, therefore, agree with earlier findings (1) which suggest that distinct populations of HRV might be circulating among neonates and older infants. Electropherotype IIA20 persisted in the United Christian Hospital, causing a protracted outbreak that lasted 8 months

TABLE 3. Spread of neonatal HRV within and outside the hospital No. of older Electope infants

IA11 IIA20 IA1 IIA2 IIA6 Others

0 0 6 6 39 433

No. of neonates in: Hospital Community

2 57 1 0 6 0

0 0 2 2 4 0

a The other electropherotypes, as described in footnote a of Table 2, were only isolated from older infants.

and that affected 57 neonates (Table 3). We do not know whether this virus also infected older infants that were interned in that hospital. However, despite its prevalence, this virus was not isolated in the community in Kwun Tong, where that hospital is located, or from patients in Queen Mary Hospital, which is located on Hong Kong Island. Electropherotypes IIA20 and IAll were only isolated from neonates while they were in the hospital. These two electropherotypes, presumably, were capable of infecting neonates only and, hence, were circulating within the confines of the hospital, where there is a concentration of susceptible hosts. The other three electropherotypes were isolated simultaneously from older infants and neonates and were also found to affect the neonates before and after they were discharged from the hospital. It appears, therefore, that the spread of neonatal strains of HRV beyond the confines of the hospital depends on their ability to infect older infants as well. DISCUSSION The study of neonatal HRV infection described here was part of a prospective study of infantile diarrhea carried out in a suburb of Hong Kong between 1983 and 1985 in which 371 infants were recruited at birth for a period of 13 months and followed up for the development of diarrhea until they were 2 years of age. As controls, we concurrently studied ambulatory patients with diarrhea who were less than 2 years of age and who were seen at one of three community-based clinics in the same suburb during the same period. The purpose of this study was to determine whether enrollment in the prospective study influenced the pattern of diarrheal diseases seen in the study cohort. To determine whether the pattern of disease may differ among hospitalized and ambulatory patients, we conducted, in parallel, a separate study of patients of less than 5 years of age who were admitted to a tertiary hospital in Hong Kong. The significance of isolation ofthe various enteric pathogens was evaluated by comparing the rates of isolation of the pathogens from children and infants who did not have diarrhea (nondiarrhea controls). Results from these studies taken together, therefore, allowed us to compare HRV infections as they occurred among the neonates within 14 days of birth, before and after they were discharged from the hospital, in comparison with infections which subsequently occurred among the same group of infants as well as with infections which occurred among older infants in the community at large. Electropherotyping and serotyping of the virus isolates further allowed us to determine whether the same population of viruses was capable of infecting the neonates and the older infants under the same epidemiological setting. In agreement with earlier findings (3, 5, 7, 9, 11), neonates

VOL. 28, 1990

ROTAVIRUSES AMONG NEONATES AND OLDER INFANTS

were frequently infected with HRV. A total of 78 episodes of HRV infection were detected in a cohort of 371 newborns. Consistent with earlier findings, none of these episodes was accompanied by diarrhea. The majority of these episodes (70 of 78) were acquired between days 1 and 3 of life, while the neonates were in the hospital, and only an additional 8 episodes occurred between days 6 and 14 after birth, after they were discharged from the hospital. The rate of hospitalacquired neonatal HRV infection was thus estimated to be 0.094 episodes per infant day. This substantially exceeded the rate of community-acquired neonatal infection, which was estimated to be 0.022 episodes per infant day. This is in agreement with previous findings which show that HRV isolates spread efficiently in institutions and are the most common cause of hospital-acquired diarrhea in infants and young children (13, 16). These findings established that a hospital stay is the single most important risk factor for neonatal HRV infection. In a serological follow-up study of 38 infants from the same cohort (18), we showed that HRV infection also occurs frequently throughout the first 2 years of infancy. The majority of these infections were asymptomatic. The infection occurred throughout the year, as did neonatal HRV infection. The infection rate was estimated to be 0.0037 episodes per infant day. Since serum specimens were obtained from these infants at 4-month intervals, this value may have underestimated the actual incidence of HRV infection, because the serological findings do not distinguish between one or more episodes of infection, which might have occurred in the interim periods. On the other hand, recent findings by Champsaur et al. (4) showed that HRV excretion is not invariably accompanied by a significant serological response against the virus. It is possible, therefore, that some episode or HRV infection might have occurred without being detected in the present study. Despite the inherent limitation of the serological approach, the incidence of HRV infection during the first 14 days of life was, nevertheless, substantially higher than that observed among the same group of infants as they grew older. The latter contention was supported by the finding that none of the 341 control children without diarrhea recruited from the same community excreted HRV. In contrast, 8 of the 371 neonates yielded the virus in their stool specimens after they were discharged from the hospital. Thus, under an otherwise similar epidemiological setting, community-acquired HRV infection occurred significantly more frequently among neonates between 6 and 14 days after birth than it did among older infants. Results from a previous study (1) suggest that distinct populations of HRV circulate among neonates and older infants. In another study in a hospital ward where both neonates and older infants were interned, Vial et al. (14) found that the same electropherotypes were isolated from both group of patients. The mean age ofthe neonates studied by those investigators was 25 days (range, 2 to 90 days), while the majority of neonatal infections that we observed occurred during the first 3 days of life. The difference in ages might explain the discrepancy that, contrary to the findings of Vial et al. (14), in the present study genotypically distinct populations of HRV circulated among neonates and older infants. We found that at least four serotypes of HRV comprising 44 electropherotypes circulated among older infants in this community during the study period. While these viruses circulated freely among the older infants in the community at large, only five electropherotypes with serotype 2 or 4 specificity or a hitherto undefined serotype

1037

specificity were detected among the neonates. Of the 70 episodes of hospital-acquired neonatal infections, 57 were caused by a serotype 4 virus strain with a distinct electropherotype (IIA20). This strain of HRV persisted in the United Christian Hospital, causing a protracted outbreak of infection among the neonates which lasted for 8 months. Two additional episodes of hospital-acquired infection were caused by a serotype 2 virus with a distinct electropherotype (IAll). Neither of these HRV strains was isolated from older infants. They seemed to circulate exclusively in that hospital and were not isolated in the community or in Queen Mary Hospital. Thus, these HRV strains seem to lack the ability to infect older infants or to spread in the community at large, and hence, they may persist excusively among neonates. As a corollary, neonates did not appear to be susceptible to infection with most of the HRV isolates from older infants. Thus, only one of the six major electropherotypes that were prevalent among older infants was isolated from neonates. Of the three electropherotypes which were isolated simultaneously from both groups of subjects, two were minor electropherotypes that were rarely isolated from older infants. Presumably, in acquiring an ability to infect neonates, these strains might have sacrificed some of their ability to infect older infants. The remaining strain was of a major electropherotype (IIA6) which was prevalent among hospitalized and ambulatory patients with diarrhea. The same virus with an indistinguishable electropherotype and the same serotype specificity was isolated from neonates. Coulson et al. (6) previously isolated HRV strains from neonates and older infants under the same epidemiological setting. Although the neonatal isolate and the isolate from older infants had the same serotype specificities and indistinguishable electropherotypes, they were differentiated by using a panel of monoclonal antibodies raised against HRV. This suggests that the virus may rapidly adapt to its new host as it is transmitted from older infants to the neonates, or vice versa, it may undergo antigenic changes in the process. Although we did not analyze the IIA6 isolates from neonates and older infants in the same way that Coulson et al. (6) did, it would not be surprising, in light of the findings of Coulson et al. (6), that they are also different from one another. From the information presented above, it seems that the ability of HRV to infect neonates and older infants is different between the two groups and is, to a large extent, mutually exclusive. Flores et al. (8) and Offit et al. (10) showed that the virulence of rotaviruses is determined, at least in part, by segment 4 of the viral genome. While we do not know whether the ability to infect neonates and older infants is encoded in the same or different segments of the viral genome, such a difference would give rise to distinct populations of the virus circulating among these two groups of infants. Hospitals and similar institutions with concentrations of susceptible neonates are favorable for the persistence of those viruses that have adapted to the neonates, more so than in the community at large. Consequently, stays in these institutions are the single most important risk factor for neonatal HRV infection. The spread of infection of the neonatal strains of the virus beyond the confines of these institutions may not be efficient because of the lack of a concentration of susceptible hosts. Therefore, the population of neonatal viruses which is prevalent in one institution is probably different from that which is prevalent in another institution. This might provide a rationale for the discrepant earlier findings that, while neonatal HRV infections are largely asymptomatic, there were, nevertheless, reports that

1038

TAM ET AL.

the infection was associated with severe diarrhea (15) and, on one occasion, even fatal enterocolitis (12). ACKNOWLEDGMENTS This study was supported by grants from the Croucher Foundation, the Hong Kong Jockey Club, and the World Health Organization (Geneva, Switzerland). We thank R. Bishop for testing the serotype specificities of some of the HRV isolates by an enzyme-linked immunosorbent assay using serotype-specific monoclonal antibodies. LITERATURE CITED 1. Albert, M. J., L. E. Unicomb, G. L. Barnes, and R. F. Bishop. 1987. Cultivation and characterization of rotavirus strains infecting newborn babies in Melbourne, Australia, from 1975 to 1979. J. Clin. Microbiol. 25:1635-1640. 2. Bishop, R. F., G. L. Barnes, E. Cipriani, and J. S. Lund. 1983. Clinical immunity after neonatal rotavirus infection: a prospective longitudinal study in young children. N. Engl. J. Med.

309:72-76. 3. Bishop, R. F., D. J. S. Cameron, A. A. Veenstra, and G. L.

4.

5. 6.

7.

Barnes. 1979. Diarrhea and rotavirus infection associated with differing regimens for postnatal care of newborn babies. J. Clin. Microbiol. 9:525-529. Champsaur, H., M. Henry-Amar, D. Goldszmidt, J. Prevot, M. Bourjouane, E. Questiaux, and C. Bath. 1984. Rotavirus carriage, asymptomatic infection and disease in the first two years of life. II. Serological response. J. Infect. Dis. 149:675-682. Chrystie, I. L., B. M. Totterdell, and J. E. Banatvala. 1978. Asymptomatic endemic rotavirus infections in the newborn. Lancet i:1176-1178. Coulson, B. S., K. J. Fowler, R. F. Bishop, and R. G. Cotton. 1985. Neutralizing monoclonal antibodies to human rotavirus and indications of antigenic drift among strains from neonates. J. Virol. 54:14-20. Fagbami, A. H., C. O. Oyejide, and F. Enahoro. 1987. Neonatal rotavirus infection in urban and rural communities in Nigeria. Trop. Geog. Med. 39:341-344.

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Distinct populations of rotaviruses circulating among neonates and older infants.

We obtained three stool specimens from each of 371 neonates. Two specimens were obtained between days 1 and 3 after birth, while they were in the hosp...
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