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With Respiratory Diseases New Viruses Observed in Children With Respiratory Diseases ROBERT M. CHANOCK, M.D., ROBERT H. PARROTT, M.D., JOSEPH A. BELL, M.D., WALLACE P. ROWE, M.D., and ROBERT J. HUEBNER, M.D. EVENTUAL control of the common respir- children, 8 of whom were studied in Washing- atory diseases depends on the determina- ton, D. C., hospitals and 27 of whom were in- tion of their etiology. Despite recent notable volved in an outbreak of febrile respiratory ill- advances in delineating the viral etiology of ness in a nursery group of a District of Co- such illnesses-at least 70 newly recognized lumbia welfare institution (Junior Village). viral agents have been described since 1948- When throat swabs were collected on one day the causes of most remain to be found. The from all infants in the affected nursery and preliminary report outlined here presents data tested for HA viruses, epidemiological analysis on two new respiratory viruses which have been indicated that there was a significant association found in children with respiratory illnesses and of type 1 HA virus isolations with febrile ill- which, while biologically related to influenza nesses (chi-square test indicated P== 0.03), thus and mumps, are also quite distinct. strongly suggesting but not proving an etio- Previously unrecognized myxoviruses classi- logical relationship. The illnesses were charac- fied in two serologic groups were isolated from terized by fever of 2 to 3 days' duration and children with respiratory illnesses during Oc- cough. Nearly half of the cases had moist tober and November 1957 (1). These two new medium to fine rales; several had coarse breath groups of agents, provisionally called hemad- sounds and rhonchi. sorption (HA) viruses types 1 and 2, were iso- Type 2 HA virus was isolated from three in- lated in monkey kidney cultures with the use fants with acute laryngotracheobronchitis of the hemadsorption technique recently intro- (croup), and more experience will be required duced by Vogel and Shelokov (2,3). Prelimi- with this agent before its etiological import- nary clinical and epidemiological observations ance in disease can be determined. indicated that these agents might be responsible Acute and convalescent serum specimens for a proportion of the common acute respira- from patients yielding either type 1 or type 2 tory illnesses in children which remain largely virus showed substantial antibody rises in unexplained despite recent advances exempli- complement fixation and hemagglutination fied by the discovery of adenoviruses (4, 5) and inhibition tests. Specimens from 82 hospital- other new agents (6-9). ized patients without respiratory illnesses did The type 1 HA virus was isolated from 35 not yield the two viruses. The contribution of the HA viruses to the Dr. Chanock, Dr. Bell, Dr. Rowe, and Dr. Huebner total respiratory disease picture cannot be as- are all with the Laboratory of Infectious Diseases, sessed at this time. However, serologic data National Institute of Allergy and Infectious Diseases, suggest that the contribution of these agents to Public Health Service. Dr. Parrott is physician-in- childhood respiratory illnesses may be substan- chief of Children's Hospital, Washington, D. C., with tial. Preliminary surveys for antibodies which Dr. Chanock is also associated. against HA viruses in the serums of 55 adults, Vol. 73, No. 3, March 1958 193 nearly all young males, showed that all had receptors sensitive to RDE (receptor destroy- neutralizing antibodies to type 1 virus, and 39 ing enzyme of Vibrio cholerae filtrate), and had neutralizing antibodies to type 2. they were sensitive to ether. The following properties indicated that the Studies of the serologic relationships of HA HA viruses are members of the myxovirus viruses to other myxoviruses, as determined by family. Both types 1 and 2 HA viruses agglu- the use of specific animal serum, are reported tinated guinea pig and chicken red cells: They elsewhere (1). The table shows distinct im- propagated in the amniotic cavity of the em- munological differences from influenza A, B, bryonated hen's egg, they possessed erythrocyte and C, mumps, and croup associated (CA) Relationship of types 1 and 2 hemadsorption (HA) virus to certain myxoviruses, as shown by rep- resentative complement fixation tests with human serums Reciprocal of CF antibody titer with 4 units of indicated antigen Infection, patient, Influenza Sendai Mumps and serum HA HA Influenza Influenza C chick CA type 1 type 2 A Asian B CAM embryo MK MK MK CAM antigen 2 extract CAM Allantoic CAM Allantoic antigen 1 antigen I antigen 1 antigen 2 antigen3 antigen fluid antigen fluid antigen antigen _-- ... Type 1 HA Patient Ha: Acute ---- <8 <8 <8 <8 <8 <8 <8 <8 <8 <8 Convalescent 64 <8 <8 <8 <8 <8 <8 <8 <8 <8 Patient Mo: Acute -- <8 <8 <8 <8 <8 <8 <8 <8 <8 <8 Convalescent 64 <8 <8 <8 <8 <8 <8 <8 <8 <8 Type 2 HA Patient Sc: Acute- <8 <8 <8 <8 <8 <8 <8 <8 <8 <8 Convalescent 64 64 <8 <8 <8 <8 32 <8 <8 <8 Patient Se: Acute 16 <8 <8 <8 <8 <8 <8 <8 <8 <8 Convalescent -- 64 64 <8 <8 <8 <8 32 <8 <8 <8 Influenza A Asian Patient Su: Acute 16 <8 <8 Convalescent -- 16 <8 32 Patient Bu: Acute 16 <8 <8 Convalescent- 16 <8 <32 Influenza B Patient Ba: Acute 8 8 <8 Convalescent -- <8 <8 64 Patient St: Acute 32 16 <8 Convalescent - 32' 8 64 Influenza C Patient Tr: Acute 8 <8 <8 Convalescent -- 8 <8 64 1 Monkey kidney tissue culture antigen. 2 Chorio-allantoic membrane extract antigen centrifuged for 1 hour at 20,000 r.p.m.-group specific antigen. 3 Chick embryo extract antigen centrifuged for 1 hour at 30,000 r.p.m. 194 Public Health Reports viruses, as shown through use of paired acute (2) V'ogel, J., and Shelokov, A.: Adsorption-hemag- and convalescent serums from patieints witl glutinatioin test for influenza virus in monkey kidney tissue culture. Scieince 126: 358-359, HA. and influenza virus infections. Aug. 23, 1957. In representative complement fixation tests, (3) Shelokov, A., V'ogel, J., and Clii, L.: Hemiadsorp- persons infected with both type 1 and type 2 tion (adsorption-hemiiagglutination) test for slhowed no rises to influenza, A, B, or C whlen viral agents in tissue culture. In press. tested against the grouLp-specific CF antig,ens (4) Rowe, W. P., Huebner, R. J., Hartley, J. W., Ward, T. G., and Parrott, R. H.: Studies of of these agents. Type 1 HA virus was showni to the adenoidal-pharyngeal-conjunctiv.lI (APlC) be different from Sendai, mumps, and CA group of viruises. Am. J. Hyg. 61: 197-218 viruses by these same serums. Type 2 IIA (19-55). virus was not related to mumps or CAi virus, (5) Huebner, R. J., Bell, J. A., and Rowe, W. P.: but slhowed a relationship to Sendai virus, The importance of adenoviruses as agents of proto- respiratory and ocular disease. In Cellular which has recently been proposed as the biology, nucleic acids, and viruises. Speciall pub- type influenza D virus (10). Childreniwho lication of the New York Ac,ademy of Sciences. were infected witlh type 2 HA virus, ancd who New York, N. Y., 1957, vol. 5, Pp. 393-402. developed complement fixing antibody for the (6) Chanock, R. MI.: Association of a new type of homologouis virus, also developed antibody for cytopathogenic myxovirus with infantile croup. J. Exper. Med. 104: 555-576 (1956). Sendai viral antigen but not for the Sendai (7) Chanock, R. M., Roizmiian, B., and Myers, R.: Re- chorio-all antoic membrane extract (soluble) covery from infants with respiratory illiness of anitigen. Guiniea pigs immunized with Sendai a virus irelated to clhimpanzee coryz.a agent. virus also developed CF an-tibody to type 2 I-IA 1. Isolations, properties, anid characterization. Amll. J. Hyg. 66: 281-290 (1957). virus, but in the hemiiagglutination inihibition (8) Price, W. H.: The isolation of a new virus asso- anid neutralizationi tests these ag,enits were ciated with respiratory clinical disease in shown to be distinct (1). hummains. Piroc. Nat. Acad. Sc. 42: 892'-896 (1956). (9) Pelon, W., Mogabgab, W. J., Phillips, I. A., aind REFERENCES Pierce, W. E.: A cytopathogenic agent isolated froiam Naval recruits waith niild respiratory ill- (1) Chanock, R. AI., Parrott, R. H., Cook, AM. K., An- miess. Proc. Soc. Exper. Biol. & Med. 94: 262- drews, B. E., Bell, J. A., Reichelderfer, T., 267 (1957). Kapikian, A. Z., an(d Huebner, R. J.: Newly (JO))Jensen, K. E., M1inuse, E., and Ackerinainn, recognized myxoviruses from childreii with re- W. W.: Serologic evideimce of Amiiericani experi- spiratory disease. New England J. Med. 25S: ence with inewborn pineuna)intiitis v-irulis (type 207-213, Jan. 31, 1958. Sendali). J. Iliimiuimol. 7.5: 71-77 (1955). International Classification of Diseases Revised Tlhe sevenithi revision of the Anaiiuial of the International Statistical Classification of Diseases, Inijiuries, anid Causes of D)eath, effective January 1958, to be used by the IUni.ted States and othier memilbers of the WVorld Ilealthi Organization for thle niext 10 years, is niow available in two voluimes, at $3.5() for thie set. Tlle first voluime conitainis the classification: the sec- on(l, the alphabetical inidex. The Ptiblic Health Conference oni lVecords and Statistics is agrain couisoli(lating) orders in the I7nite(l States. Orders and(I chiecks payable to that orgalaiza- tioni i-ay be addiesse(d c/o T)epartinent of Health, Eduicationi, and Welfare, National Office of Vital Statistics, Washilnlg- toll 25, 1)..C. Vol. 73, No. 3, March 1958 195 New Members of the PHR Board of Editors Dr.
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