EPIDEMIOLOGY OF RI (RI-67) GROUP RESPIRATORY VIRUS INFECTIONS IN RECRUIT POPULATIONS x

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1 EPIDEMIOLOGY OF RI (RI-7) GROUP RESPIRATORY VIRUS INFECTIONS IN RECRUIT POPULATIONS x BY M. B. TTTLT.EMAN, J. H. WEENEB, H. E. DASCOMB,» B. L. BUTLEB AND M. T. STEWABT» (Received for publication April, ) Acute febrile respiratory illness is a major cause of disability in military populations, particularly among recruits ( ), as well as in civilian populations. Recently this laboratory reported the discovery of a new family of antigenically heterogeneous viruses designated the RI (prototype strain RI-7) group (-7). These agents are prevalent among soldiers and appear to be responsible (-) etiologically for the majority of cases of undifferentiated acute respiratory disease (ARD) (, ) and those cases of primary atypical pneumonia (PAP) not associated with the development of cold or Streptococcus MG agglutinins. As a result of the development of suitable virological and serological methods () it has been possible to conduct epidemiological investigations of the disease and infections attributable to the viruses of the RI group. This paper presents the findings of such an investigation among recruits receiving basic training at Fort Dix, N. J., during. MATERIALS AND METHODS Composition of the military population. During the time of the present From the Department f Virus and Biekettsial Diseases, Army Medical Service Graduate School, Washington, D. C, and the Port Dir Health Center, U. S. Army Hospital, Fort Dix, N. J. Present address: Department of Medicine, Louisiana State University, New Orleans, La.»The technical assistance in these studies of L. B. Hundley, Pfc, ATJ, and E. Greene, Pfc, AtTS, is gratefully acknowledged. study the principal function of Fort Dix was to provide training, both basic and advanced, for newly inducted soldiers. Three fourths of the total post strength was comprised of an infantry division which was the training organization. Approximately two thirds of the personnel of this division were recruits in training and the rest were the operating personnel responsible for carrying out the training program. The other units on the post were organisations which operated the reception center, rendered services to the training division or maintained the post. Most of the recruits were inducted from the First Army Area in the Northeastern United States. These soldiers were principally men drafted for a -year period but also included a scattering of volunteers who had enlisted for -, - or -year periods. The majority of the men were between and years of age, with a range from to years. Only a small fraction was colored. The training program was organized in cycles which consisted of weeks of basic training followed by a similar period of advanced training. Each recruit was assigned to a training company to days after arrival at the reception center on the post and passed through a period of military orientation which lasted approximately week (precyele) before the actual training period began. Recruits were not permitted to leave the post until the end of either the fourth or fifth week of AM.J.HTO., VOL. : - Downloaded from on March

2 HTTJiKMAN, WERNER, DASOOMB, BUTLEB AND STEWABT training when each man was given a -day pass. During the sixth week of basic training cycle, each company spent a period of days in bivouac away from its permanent quarters. After completion of the basic training cycle the troops were dispersed. About one third of the men remained at Fort Dix while the remaining two thirds were sent to other posts for advanced basic or specialized training. The recruits were billeted in barracks which housed between and men, each barracks being occupied by men from the same company. Mess halls served men from one or from several (consolidated messes) companies and opportunity existed for the personnel to mingle with other units at post exchanges, service clubs, theatres, etc. Two units were selected for intensive study. Company K was chosen to represent a company activated during a high prevalence of acute respiratory illness. It was formed on January and,, and started precycle orientation on February. Basic training was completed on April after which the men were dispersed for advanced training. Company D was studied as a company organized during a period of low prevalence of respiratory disease. The company was organized on July and,, and had its basic training between August and September. Method of study. All the recruits in the two companies were bled during the second week in company (first week of basic training) and again at periodic intervals during the following (Company K) or (Company D) weeks. The few soldiers in each company who began training earlier and were being recycled were excluded from the study. Men being recycled from companies K or D for medical or other reasons were bled regardless of the fact they had left the unit. The late blood samples of men who had left the post for advanced training were obtained by medical officers at the recruit's new location. In addition, all men of these companies who were hospitalized with respiratory illness during the basic training period were bled at the time of admission to the hospital and again to weeks later. All the sera were tested for RI group antibody by the CF technique and, in addition, some of the sera were examined for neutralizing antibody. Each man in the company was observed for occurrence of respiratory illness and these findings were correlated with the results of the serological tests. All men attending sick call were seen at a dispensary by a medical officer who recorded the patient's temperature and the clinical findings. Patients with respiratory illness were hospitalized, placed on quarters status, or returned to duty depending upon the physician's judgment of the severity of the illness. Usually, but not always, patients with a temperature of F or more were hospitalized. In the present report, patients who were seen only at the dispensary are referred to as dispensary cases and those who were hospitalized after initial observation at the dispensary are called hospital cases. Clinical information was available during basic training only since the majority of the men were transferred off the post after completing their basic course.. The clinical diagnosis of the respiratory illness manifested by the patients was based usually on the most prominent features of the disease. The more common designations were acute pharyngitis, tonsillitis, bronchitis, pneumonitis or simply upper respiratory illness (URI). Designations of common Downloaded from on March

3 EI-7 EESPIBATOET INFECTIONS IN HILITABY KECKUITS cold, rhinitis or tracheitis were used less frequently. X-ray examinations of the chest were made of all men hospitalized with respiratory illness at Fort Dix. During the period of the study, roughly per cent of such patients had a demonstrable pneumonitis during their illnesses. Other than the RI group infections, there were no notable epidemics of diseases of known etiology during the entire period of the study. Routine throat cultures taken from cases of respiratory disease at the time of admission to the hospital or dispensary were positive only occasionally for beta hemolytie Streptococci and rarely for N. intracellularis. The latter finding was consistent with the low incidence of meningococcal disease at that time. Influenza was notably absent throughout the world during () except for a sporadic occurrence of influenza B and this was also true of Port Dix. Laboratory procedures Serum specimens. All samples of blood withdrawn during the course of shown. the study were collected in vacuum containers and transmitted immediately to the Army Medical Service Graduate School where the sera were separated from the clots. They were then frozen and maintained in the frozen state at C except when thawed for testing. RI group serology. The complementfixation (CF) and neutralization tests were performed according to methods described previously (). In the CF tests, RI-7 virus infected HeLa * tissue-culture () material containing group-specific CF antigen common to the entire family of RI viruses (, ) * The cultures of HeLa cells employed in these investigations were obtained from Microbiological Associates, Inc., Bethesda, Md. was employed as antigen. The neutralization tests were carried out in HeDa cell tissue culture employing the prototype RI-7 strain and also the RI-- virus. The latter agent was recovered from a patient with ARD at Fort Dix during January,. Neutralization tests performed with paired sera from human cases of RI group infection showed these two viruses to be markedly different antigenically (). Together, they appeared to cover the greater part of the range of antigenic variation among the strains which cause illness in soldiers during the contemporary period. RESULTS Occurrence of respiratory illness at Fort Dix. The incidence of admissions for all respiratory disease at Fort Dix, N. J., during the period from September,, through December,, is shown by weeks in figure. The usual seasonal pattern of occurrence with high rates during the cold months and low rates during the warm season is clearly The peak incidence occurred during the first week in February when the annual rate per, men exceeded. As indicated on the chart, the studies made with Companies K and D were, respectively, during periods of high and low prevalence. Previous observers (-) have shown that the incidence of respiratory disease in recruits is related to the season of the year, the over-all prevalence of respiratory illness on the post and the stage of the training cycle. These observations are clearly substantiated by the present study as is illustrated in figure. It is seen that a sharp epidemic of respiratory illness occurred in Company K in early training and reached a rate of per, per week Downloaded from on March

4 HTTITJKMAN, WEBNEB, DAHB, BUTLEB AND STEWABT o 7- eoo WEEK.: SEPT BLEEBNO DATES' COMPANY K COMPANY D I I I I I I I I I I I I I I ' I I I I I II M I I I I I I I I I I I I I I I (mj F M A M J C^J A S N D FIGURE. Admission rates, "total respiratory disease," Port Dix, New Jersey, showing periods when epidemiological investigations were made. COUPANYX (F B -IURCH) FIOITBB. Hospital admission rates, "total respiratory disease," among recruits in two companies dnring winter or summer training. Downloaded from on March

5 BI-7 RESPIBATOBT INPBOTIN IN MIUTABT BECBUIT TABLE Frequency tuer dittribution of RI group CF antibody in sera of recruits bled at periodic intervals, Fort Dix, New Jersey, {"Vim Tf TIT Date bled Week in company *. No. of sen ahowing titer S Number podtire Ueomeinomean K ( men) // / / / Raw recruits ( men) // Precompany (day - on poet) D ( men) // / / / * Numbers are reciprocals of serum titers, equals lees than in., the lowest serum dilution tested. by the second week of training (, per, per year) with rapid decline thereafter. By contrast, there were very few cases of respiratory illness in Company D which trained during the summer months when the over-all prevalence on the post was low. In this company, only sporadic cases of respiratory disease occurred during the entire -week period of observation. Development of BI group CF antibody in recruits. The distribution of recruits according to RI group CP antibody at various periods during their training is shown for Companies K and D in table. Of the men in Company K trained between February and May, ( per cent) had detectable CF antibody in their initial specimen drawn weeks after activation of the company. At the end of the eighth week in company, this had increased to ( per cent) and showed no further increase during advanced training. At the same time as the proportion of men showing CF antibody decreased, the mean titer of the group also rose from in at week to in 7 at week. This declined to in by the seventeenth week. These findings indicate that infection with the BI group viruses was common during the basic training period and reached its peak by the eighth week. Since the first bleeding of the men in Company K was not made until the second week in company, there was ample opportunity for infection and development of CF antibody among the men after arrival on the post and before the initial sera were obtained. In order to estimate the extent to which this might have taken place, raw recruits were bled within days of arrival on Downloaded from on March

6 HILIiEMAN, WESNEB, DASCOMB, BUTLEE AND STEWABT the post during the same general time period and tested for RI CF antibody. In this group, the proportion of sera which was positive was only slightly below ( per cent) that found in Company K during their second week. Thus it is reasonable to assume that the serological pattern among the men in Company K at the initial bleeding had not changed appreciably from that on arrival at Port Dix weeks earlier. The findings among the men of Company D trained during August through October presents a sharp contrast to those of Company K. As in Company K, roughly one half of the men had CF antibody at the time of the initial -week bleeding and the mean titer was in but only a small number of men developed detectable CF antibody during the -week period of observation. This suggested that the rate of infection with RI group viruses was very low among soldiers who underwent training during the late summer. Correlation of increase in RI antibody with respiratory Ulness. The CF findings with the sera collected in the routine samplings as well as the acute and convalescent specimens from patients who were hospitalized were analyzed to determine what proportion of the recruits developed diagnostic increase (-fold or greater) in antibody during winter (Company K) or summer (Company D) training. These data which are summarized in table and presented graphically in figure revealed that 7 ( per cent) of the men in Company K showed a significant increase in antibody titer during the 7-week training period while TABLE Development of significant* increase in RI CF antibody among recruits during.winter or summer training, Fort Dix, New Jersey, Composite All men in company Group I. Men with initially negative CF tertt Group II. Men with initially positive CF tertt Company K. February-May, Total strength No. weeks in company No. men showing significant rise in titer (cumulative) 7 Company D. August-October, Total strength No. weeks in company No. men showing significant rise in titer (cumulative) * Significant increase in CP titer is -fold or greater, f Two weeks in company. Downloaded from on March

7 EI-7 RESPIRATORY INFECTIONS IN MILITARY RECRUIT COMPOSITE ALL MEN IN COMPANY GROUP I. MEN WITH INITIALLY NEGATIVE CF. TET GROUP a. MEN WITH INITIALLY POSITIVE CF. TET COMPANY K- FEBRUARY-MAY IS PERCENTAGE IHOWDM SIGNIFICANT RISE IN WEEK IN COMPANY ui o - LJ g «H X o. 7 7 COMPANY - AUGUST-OCTOBER MEN MEN IOB MEN 7 WEEK IN e COMPANY FIOUEE. Percentage of recruits with significant increase in RI group complementfliation antibody during winter (Company K) or summer training (Company D), according to time of rise and referrable respiratory illness. * Clinical information not available for men who showed increase in antibody after the eighth week (Company K) or ninth week (Company D). only ( per cent) failed to do so. This finding would seem to indicate that at least per cent of the men suffered an infection with RI group viruses during their training. Thirty-nine per cent of the soldiers showed increase in titer by the fourth week of residence in the company and an additional per cent between the fourth and eighth weeks; only per cent developed a rise in titer during the final - to 7-week period when most of the men were no longer at Port Dix and when the respiratory disease rates on the post were falling sharply. In contrast to Company K, only ( per cent) of the men in Company D who trained during the summer period showed an increase in Downloaded from on March

8 HUJLEMAN, WERNER, DASOOMB, BUTLER AND STEWART RI CP antibody during the first weeks in company, indicating that the infection rate during the summer was very low as compared with that during the winter. The extent to which clinically apparent illness or inapparent disease accompanied infection with RI group viruses is summarized in table and is shown graphically in figure. Since the companies were dispersed after the basic training period and most of the men transferred to other stations, clinical data were available for Company K only during the first weeks in company and for Company D during the first weeks. The increase in RI antibody can be correlated precisely with the occurrence of the illness of the cases which were hospitalized since blood specimens were taken at the time of hospital admission and again during convalescence (see table ). The relation between titer elevation and the occurrence of respiratory illness which, was treated without hospitalization at the dispensary is less precise since only routine samplings of blood were collected from these men. TABLE Correlation between respiratory illness and antibody increase among recruits during winter or summer training, Fort Dix, New Jersey, * Person* ihowinjz significantf increase in CF titer by end oi given period in company Composite, All men in company Group I. Men with initially negative CF test Group II. Men with initially positive CFtest Company K. February-May, Total strength No. weeks in company Preceding illness (cumulative) Hospital! Dispensary! None 7 7 Company D. August-October, Total strength No. weeks in company Preceding illness (cumulative) Hospital! Dispensary! None to to * No clinical information available for Company K, weeks through 7, or for Company D, weeks through. t Significant rise in titer is -fold or greater.! Increase in titer can be related to illness. Downloaded from on March

9 BI-7 RESPIBATOBT INFECTIONS IN MUJTABY RECRUITS 7 It is possible, therefore, to make only a rough estimate of the mutual relationship between antibody increase and respiratory illness handled at the dispensary. The findings with Company K showed that per cent of the men who developed significant rise in antibody titer did so while they were hospitalized with a respiratory disease. An additional per cent of the men who showed significant antibody increase were treated at the dispensary for a respiratory sickness which could be related in time to the positive serological findings. The remaining per cent of the individuals who developed increased amounts of BI antibody failed either to report to the dispensary or to enter the hospital and it is inferred that the majority of these persons suffered either a mild or an inapparent infection. During the period of study there was remarkably little respiratory illness among the men in Company K requiring medical attention which could not be related temporally to a significant increase in RI antibody. Only 7 per cent of the men in the company were admitted to the hospital or TABLE RI CF test results obtained in the cases of hospitalized respiratory Ulness among recruits in two companies Company K ( men) D ( men) Total number of cam Cues showing tfterrise* (-fold or greater) No. Per cent Cues not showing significant titer rise* (-fold or MS) No. Per eent * Acute-phase illness and week-blood specimens compared. Significant increase in titer is -fold or greater. TABLE Results of neutralization tests with sera from SI recruits in Company K who showed significant* increase in RI CF antibody Recruit* with rise in CF antibody Status Hospitalized casesf No illness Total DO. No. of recruits showing significant* inorease in neutralising antibody against RI-«7 7 RI-- RI-7or RI-- No. 7 Per cent Significant increase in CF titer is -fold or greater. t Includes cases treated at the dispensary. dispensary with respiratory illness presumably caused by agents other than the RI viruses. As would be expected, the occurrence of hospital and dispensary illness in Company D was infrequent and presented roughly the same proportions of apparent and inapparent illness as shown in Company K. The significance of the relationship between the occurrence of respiratory disease and a rise in antibody titer is supported by the data obtained when the sera from all the hospitalized cases in the company are studied. Thus, as shown in table, men from Company K were hospitalized with respiratory disease during the first weeks in the company and of these ( per cent) showed a diagnostic increase in CF titer during the course of their illnesses. The significance of increase in amount of CF antibody was substantiated further by the neutralization test results summarized in table. The sera of of the hospitalized cases were tested for rise in neutralizing antibody. Twentyone ( per cent) of these showed significant rises against the RI-7 or RI- - strains. The CF antibody in- Downloaded from on March

10 HILLEMAN, WEBNEB, DASCOMB, BUTLEB AND STEWART TABLE Distribution, CF and neutralizing antibody in acutephase serum samples, SS hospitalized patients* (company K) who showed subsequent rise in CF and neutralizing antibody CF titer for RI viruses ot.j Totals Ot Neutralization titer against RI-7 t o o to o Ot RI-- * Includes patients treated at the dispensary., in the neutralization tests means titer less than in, and in the CF teat, less than in., the lowest dilutions of serum tested. t Numbers are reciprocals of CF or neutralizing antibody titers. creases in 7 of cases of no illness ("inapparent infection") were similarly confirmed by the neutralizing antibody tests. It was observed further (table and figure ) that roughly one half of the men in both companies K and D had detectable antibody in their initial serum specimens. The occurrence of subsequent CF antibody titer increase and of respiratory illness, however, was not appreciably influenced by the presence or absence of CF antibody in the initial serum specimen. A reasonable explanation for these seemingly paradoxical findings lies in the observation that most of the sera which contained CF antibody on the initial bleeding were devoid of neutralizing antibody against the strains of virus -which were encountered during the study. Thus, as shown in table, only acutephase serum samples from serologically proved cases of RI infection contained demonstrable neutralizing anti- n body for the RI-7 strain and none of these had neutralizing antibody for strain RI- which was also prevalent at the time even though they presented CF titers ranging from to in. It is reasonable to assume that the CF antibody which was present resulted from prior infection with other viruses of the RI family which differed antigenically from the test strains. Serological 'pattern in RI growp infections. To determine the serological pattern in RI group infections, sera collected from hospitalized cases of the disease during the acute illness and at varying time periods thereafter were tested for neutralizing and CF antibody. The patients chosen for study were from the epidemic which occurred at Fort Leonard Wood ( cases) during - (7) or in the present study at Fort Dix ( cases). All showed a significant (-fold or greater) increase in both CF and neutralizing antibody in their convalescent sera. The findings summarized in table 7 revealed that the CF and neutralizing antibody titer rises during convalescence (weeks through 7) were roughly of the same magnitude and the serum titers did not decline appreciably by the end of to months. Both the CF and neutralizing antibody titers diminished during the year following; however, all specimens still contained CF antibody and of the demonstrated neutralizing capacity. These tests indicated that the CF and neutralizing antibodies were about equally persistent. DISCUSSION It has been known for many years that newly inducted soldiers provide a fertile field for the development of acute respiratory illness, particularly during the winter months (-). The Downloaded from on March

11 EI-7 RESPIRATORY INFECTIONS IN MILITARY RECRUITS TABLE 7 Pattern of CF and neutralizing antibody in hospitalized patients with RI group infections, individual liter values Location of patients Time of collection of serum sample.» No. showing CF titer Geometric mean titer Fort Leonard Wood, Mo., Acute week year Fort Dix, N. J., Acute -7 week - month 7 7 No. showing neutralization titer (RI-7) * Fort Leonard Wood, Mo. Acute week year Fort Dix, N. J. Acute -7 week month 7 * Numbers are reciprocals of serum titers. occurrence of these illnesses appears to be conditioned principally by bringing together a large number of susceptibles at an unfavorable season of the year. This occurred in the present study and the assembling of the raw recruits in Company K during February promptly resulted in an epidemic of acute respiratory illness which had its peak in the second week after the men were first brought together in the company. The initial sera from the men in Company K were obtained at the height of an epidemic of acute respiratory disease weeks after their training began. At that time, per cent showed detectable CF antibody and this increased to per cent by the end of the eighth week. During this period, 77 per cent of the men showed significant (-fold or greater) rises in antibody titer as measured by the CF test. These rises in antibody occurred in the presence of illnesses of varying severity and in recruits who had no apparent disease. It is inferred that all persons showing significant antibody increase during this period were infected with RI group viruses. About one fourth of these men had illnesses which required hospitalization and a similar proportion had illnesses which were treated on an out-patient basis at the dispensary. The remaining one half did not seek medical attention at any time. It would seem that this latter group can be classed as having very mild or inapparent infections. One factor of unquestioned importance in the incidence of acute respiratory disease is the season of the year. Thus, it has been commonly observed Downloaded from on March

12 HEUiBMAN, WEBNEB, DASCOMB, BUTLEE AND STEWART (-) that units which underwent training during the warm months of the year experienced a low incidence of acute respiratory disease in contrast to the high rates which were experienced by units training during the winter. This was also true of Company D in the present investigation and, as might be expected, the incidence of infection with viruses of the HI group was also low; only per cent of the men presented evidence of infection during their first weeks in company. It was shown in studies carried out by the Commission on Acute Respiratory Diseases (, cf., ) at Port Bragg during the years through that battalions which began training during late summer and fall, when the over-all respiratory disease rates were low, did not experience epidemics until the following December or January after they had completed to months of training. The epidemics which occurred at this time were more irregular and less sharply denned but the total admission rates were comparable to those of battalions which arrived during the winter. Because of the dispersal of the troops in Company D in this study to permanent assignments after training was completed, it was not possible to determine whether or not these men also experienced high respiratory rates during the following winter. The low rate of infection with RI group viruses seemed to indicate very little increased resistance to these agents and the great majority of the men in the company would be expected to be quite susceptible to RI group infection during the following winter season. Thus, they could not be considered "seasoned" with respect to the RI viruses. The CF test for RI group infections measures antibody against a noninfectious "soluble" component which is smaller in size than the viral elementary bodies and may be separated readily from them (). The apparent lack of effect of antibody against the "soluble" component in preventing RI infection among the soldiers in the present study is similar to the absence of protective effect of "soluble antigen" antibody in other viral diseases such as influenza, vaccinia and lymphoeytic choriomeningitis (see ). In view of the absence of significant amounts of neutralizing antibody against the epidemic RI strains in the present group of men, it seems likely that the CF antibody which was present in the soldiers at the beginning of their military experience resulted from prior experience with other agents of the general RI family such as the latent tonsil and adenoid degenerative viruses described by Rowe, Huebner and their associates (, ). The human population appears to be a reservoir of viruses of the RI family. The present findings' of a low but continued prevalence of RI infections among the recruits in Company D during summer and fall training together with the previously reported () occurrence of proved RI disease throughout all seasons of the year suggest that person-to-person contact between susceptibles and individuals with clinically apparent or inapparent disease would be sufficient alone to maintain the virus in human populations. An additional source of infection might be in the activation of "masked" virus in the respiratory tract where, as shown by Rowe, Huebner et al (, ), certain agents of this family of viruses may exist in latent or inapparent form. The persistence of CF and neutralizing antibody for periods of year or more after infection suggests that both the CF and neutralization tests may Downloaded from on March

13 EI-7 RESPIRATORY INFECTIONS IN MILITARY RECRUITS be of value in serological surveys to determine prior experience of the population with these agents. The CP test is of advantage because of its simplicity and rapidity of performance. However, this test measures antibody against the group-specific "soluble" component (, ) of viruses of the RI family and a positive test must be interpreted to indicate prior experience with one or more members of this family of antigenically heterogeneous agents. For the purpose of detecting previous infection with any particular one of these viruses, the highly type-specific neutralization test must be employed. SUMMARY Infection with viruses of the RI family (RI-7 prototype) was highly prevalent among soldiers who underwent basic training at Fort Dix, New Jersey, during the winter of. Seventyseven per cent of the men developed significant increases (-fold or greater) in CF antibody for these agents during the first weeks at camp and per cent during the first 7 weeks; it is inferred that all these persons had become infected with RI viruses during that period. The CF titer rise in a representative sample of the sera was confirmed by similar increase in neutralizing antibody against one or both of two viral strains which were predominant in the epidemic. Roughly one fourth of the men who became infected had a corresponding respiratory illness which required hospital treatment while the disease in another one fourth of the persons was sufficiently mild to permit treatment at the dispensary alone. The remaining soldiers did not seek medical attention and had very mild or inapparent infections. In contrast to the winter findings, only per cent of a group of recruits who trained at Fort Dix during the summer of showed an increase in RI antibody. These men had little experience with the RI viruses during their basic training and would not be expected to be "seasoned" to the RI agents as were the soldiers who trained during the winter. Roughly per cent of the men who trained at Fort Dix had detectable CF antibody in the initial serum sample but neutralizing antibody for the strains of virus predominant in the epidemic was notably absent. The CF antibody was against a "soluble" group-specific component of the family of RI viruses and did not appear to exert a "protective" effect either in preventing subsequent increase in titer or clinical illness. In cases of RI infection, the maximal levels of neutralizing and CF antibody were reached by the second to fourth week after onset of illness and declined gradually to low but detectable levels during the following year. A reservoir of viruses of the RI group clearly resides in the humaj population and the disease may be maintained by contact between infected and susceptible individuals. The possible activation of latent "masked" virus from healthy in-. dividuals might also constitute a reservoir of infection. REFERENCES. Commission on Acute Bespiratory Diseases. Acute respiratory disease among new recruits. Amer. Jour. Pub. Health,, : -.. Commission on Acute Bespiratory Diseases. Epidemiology of atypical pneumonia and acute respiratory disease at Fort Bragg, North Carolina. Amer. Jour. Pub. Health,, : -.. Sartwell, P. E. Common respiratory disease in recruits. Amer. Jour. Hyg.,, S: -. Downloaded from on March

14 HXLLEMAN, WEBNEB, DASCOMB, BUTLER AND STEWABT. Duff, F. L. The Effects of Geography, Season and Length of Military Service upon Common Respiratory Disease in the United States Army. Thesis submitted to the School of Hygiene and Public Health of the Johns Hopkins University in conformity with the requirements for the degree of Doctor of Public Health,, pp.. Hilleman, M. R., and Werner, J. H. Becovery of new agent from patients with acute respiratory illness. Proc. Soc. Exper. Biol. and Med.,, : -.. Hilleman, M. R., Werner, J. H., Daseomb, H. E., and Butler, R. L. Epidemiologic investigations with respiratory disease virus RI-7. Amer. Jour. Pub. Health,, : Hilleman, M. R., Werner, J. H., Adair, C. V., and Dreisbach, A. R. Outbreak of acute respiratory illness caused by RI-7 and influenza A viruses, Fort Leonard Wood, -. Amer. Jour. Hyg.,, : -7.. Dingle, J. H., Ginsberg, H. S., Badger, G. F., Jordan, W. S., Jr., and Katz, S. Evidence for the specific etiology of "acute respiratory disease (ARD)." Trans. Ass'n Amer. Physicians,, 7: -.. Davis, D. J. Occurrence of influenza, July to June. Pub. Health Rep.,, :.. Scherer, W. F., Syverton, J. T., and Gey, G.. Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. Jour. Exper. Med.,, 7: -7.. Hilleman, M. R., Tousimis, A. J., and Werner, J. H. Biophysical properties of respiratory disease virus RI 7. Abstract, to be published in Bact. Proceedings,.. Hilleman, M. R., Werner, J. H., and Stewart, M. T. Antigenic variation among RI-7 group viruses: diagnostic problems. Abstract, to be published in Federation Proceedings,.. Smadel, J. E. Serologic reactions in viral and rickettsial infections. Chapter, Viral and Rickettsial Infections of Man, edited by T. M. Rivers. Second edition. J. B. Lippincott Co., Philadelphia,, pp. -.. Rowe, W. P., Huebner, R. J., GUmore, L. K., Parrott, R. H., and Ward, T. G. Isolation of a cytopathogenic agent from human adenoids undergoing spontaneous degeneration in tissue culture. Proc. Soc. Exper. Biol. and Med.,, : Huebner, R. J., Rowe, W. P., Ward, T. G., Parrott, R. H., and Bell, J. A. Adenoidal-pharyngeal-conjunctival agents. A newly recognized group of common viruses of the respiratory system. New Eng.' Jour. Med.,, S: 77-. Downloaded from on March