Spread of influenzaviruses A/England/42/72 and A/Hong Kong/1/68

Bull. Org. nwnd. Sant6 1 1974, 50, 475-478 Bull. Wid Hlth Org. Spread of influenzaviruses A/England/42/72 and A/Hong Kong/1/68 A serologic study in Nepal and Calcutta, India * V. 0. SOUSA,1 I. L. GRAVES,2 & S. PYAKURAL 3 Seroconversion for A/England/42/72 (H3N2) virus occurred in a child in Calcutta in August 1971, one month after the virus was first isolated in India. During the following 5 months a small increase was observed in the geometric mean titres (GMT). In mid-1972 the virus was in Kathmandu, Nepal, where the children had a higher GMT than the adults. The GMT increased sharply during 1972 and early 1973 and this increase was accompanied by an increased number of hospital admissions for respiratory diseases. Among the people in the isolated village of Lang Tang (3 500 m elevation), the GMT and prevalence for both A/England/42/72 and A/Hong Kong/1/68 (H3N2) were less than 50 % of the Kathmandu values. After July 1968, worldwide recurrent outbreaks of influenza were reported (4) to be associated with the virus A/Hong Kong/1/68 (H3N2). The virus A/England/42/72 (H3N2) was first isolated in Coonoor, South India, in July 1971 (11) and was responsible for influenza outbreaks in Malaysia, Singapore, the South Pacific area, and Australia, as well as in the United Kingdom, France, and the Federal Republic of Germany in 1972 (5). In the USA several outbreaks, confirmed by virus isolation, occurred in civilian and military populations. The Center for Disease Control reported that in the first week of January 1973, pneumonia-influenza deaths in 122 US cities exceeded the expected levels and this increase persisted for 10 weeks (1). MATERIALS, METHODS, AND RESULTS The presence of A/England/42/72 and A/Hong Kong/1/68 influenzaviruses in India and Nepal was serologically examined by means of standard tech- * Requests for reprints should be addressed to The Johns Hopkins CMR, 550 N. Broadway, Baltimore, Maryland 21205, USA. 1 I.R.A.P. Fellow, The Johns Hopkins CMR, Kath- mandu, Nepal. ' Associate Professor, Department of Pathobiology, The Johns Hopkins University, Baltimore, Maryland. ' Head, Veterinary Division, H.M.G. Ministry of Agri- culture, Kathmandu, Nepal. niques. Sera that gave antibody titres > 1/40 when treated with a receptor-destroying enzyme and tested with type 0 human erythrocytes were considered to be positive (8 units of antigen were used) (7). All comparisons were based on haemagglutination inhibition (HI) tests that were carried out simulta- neously. The geometric mean titre (GMT) of the positive sera was found to be a more sensitive mea- surement than the prevalence (i.e. (number posi- tive/total tested) x 100) for determining whether A/ England/42/72 antibody was present in the popu- lations examined. In addition to prevalence, Hoskins et al. (8) also used the GMT for determining whether A/England/42/72 or A/Hong Kong/1/68 antibodies were present in the sera before and after vaccinations. In Kathmandu, which is 1 340 m above sea level, 328 sera collected in August and September 1972 from donors aged 2-45 years were compared with 105 sera taken from a population of similar age structure between November 1972 and January 1973. The age-specific prevalences and GMT of HI anti- bodies for A/England/42/72 and A/Hong Kong/1/68 are given in Table 1. Included in Table 1 for com- parison are data on 57 sera taken in October 1972 from residents, aged 16-45 years, of Lang Tang village. These sera represent approximately 30% of the population of the village, which is located 50'km due north of Kathmandu at an altitude of 3 500 m. To compare the data from Nepal with those from India, tests were performed on sera from children 3213 - 475 V. 0. SOUSA ET AL. Table 1. Prevalences a and geometric mean titres of haemagglutination inhibition antibodies for influenzaviruses A/England/42/72 and A/Hong Kong/1/68 in sera from Kathmandu and from Lang Tang village, 1972-73 A/England/42/72 A/Hong Kong/i /68 Place and age group Aug.-Sep. 1972 Nov. 1972- Au.-Sep. 1972 Nov. 1972-(years) Jan. 1973 Au-e.a92 no. 1972- prevalence GMT prevalence GMT prevalence GMT prevalence GMT Kathmandu 0-9 72 947 63 453 66 246 56 74(23/32) (10/16) (21/32) (9/16) 10-19 63 193 78 525 71 80 78 238(26/41) (7/9) (29/41) (7/9) 20-29 56 126 83 218 71 84 73 146(100/177) (43/52) (126/177) (38/52) 30-39 49 89 75 320 56 89 75 143(29/59) (18/24) (33/59) (18/24) 40-49 53 190 75 320 73 114 75 101(8/15) (3/4) (11/15) (3/4) all ages 57 164 77 284 68 96 71 138(188/328) (81/105) (223/328) (76/105) Lang Tang b 16-45 30 77 32 59(17/57) (18/57) a Expressed as percentages; within parentheses b These sera were taken in October, 1972. 0-12 years of age. Sera were collected in Kathmandu during 2 periods of 4 months each (June-September 1972, and mid-October 1972-mid-February 1973), and in Calcutta during periods of 2 months (August and September 1971) and 4 months (October 1971- January 1972). In Nepal, 3 places were chosen so that comparisons could be made: Pokhara, a city 160 km west of Kathmandu at an altitude of 790 m; Biratnagar, a town lying on the Nepali-Indian border at 150 m; and Tangboche, a monastery 110 km east of Kathmandu at 4 100 m. The GMTs and the prevalences of A/England/42/72 and A/Hong Kong/ 1/68 antibodies in the sera of the children tested are presented in Fig. 1. Paired sera collected during July-October 1971 from 21 children in Calcutta were tested for A/ England/42/72 and A/Hong Kong/1/68 antibodies. In one 21/2-year-old male child's serum taken on 26 July 1971, the HI titre for A/England/42/72 anti- body was less than 1/40. A second serum sample taken on 16 August 1971 had an antibody titre of 1/60. In all, 63 sera were tested and the GMT of 32 that were positive for A/England/42/72 was are the proportions No. positive/total tested. 80, whereas the GMT of 19 that were positive for A/Hong Kong/1/68 was 83. Thirteen of the 21 paired sera had HI antibodies, and 10 pairs were tested on single radial diffusion plates (10) with X-31 (H3N2) WonIKK I s i it1 1. AaTemEMMI A i I I A Fig. 1. Titres of haemagglutination inhibition antibodies for A/England/42/72 (H3N2) and A/Hong Kong/1/68 (H3N2) influenzaviruses in children from India and Nepal, and the ratios of No. positive/No. tested during 1971-73 476 SPREAD OF INFLUENZAVIRUSBES MJ J^S O ND J F MA M JJ A S UN DJ F MAM"J J AS 0 Fig. 2. Ratios and percentages of No. of admissions for respiratory diseases except tuberculosis/total No. of admissions to the Children's Hospital, Kathmandu, Nepal, during 1971-73 virus. Antibody rises were detected in 3 children, one of whom showed the rise in HI antibody men- tioned above. From the records of the Kanti Hospital (Kath- mandu Children's Hospital), the ratios of the number of admissions for respiratory disease, excluding tuberculosis, to the total number of admis- sions were determined for each month (Fig. 2). D)ISCUSSION The appearance of influenzavirus A/England/42/72 in July 1971 raised the possibility that its spread might become worldwide. Its predecessor, A/Hong Kong/1/68, had spread considerably in India having been reported from Madras (12), Vellore (9), and Assam (3). The present task was to determine if A/England/42/72 virus was spreading in India and Nepal by comparing the GMT and the prevalences of antibody for it with those for A/Hong Kong/1/68 virus. The seroconversion among hospitalized children in Calcutta indicated the presence of A/England/42/ 72 virus 1 month after it had been isolated in Coo- nloor, South India. The sensitivity of the radial diffusion test over that of the HI test for detecting the relative differences in antibody concentration was also apparent (11). The two samples drawn from the Kathmandu population during August and September 1972 and from November 1972 to early January 1973 showed that the GMT for A/England/42/72 virus was higher than that for A/Hong Kong/1/68 virus in every case but one. The highest titres were found in the young- est and oldest age groups. The increases in the over- all prevalence and in the GMT were greater for A/ England/42/72 virus than for A/Hong Kong/1/68 virus during the periods when the epidemic was spreading in Kathmandu (Table 1). The GMTs were consistently lower for the Lang Tang residents than for the Kathmandu population (Table 1). Although the Lang Tang valley is physic- ally remote from Kathmandu, it is possible for its residents to walk to Kathmandu in 4 days. The sera studied were obtained from 2 villages in Lang Tang valley near the airfield. The remoteness was prob- ably responsible for the fact that the prevalence and GMT of A/England/42/72 antibodies in the sera from Lang Tang villagers were lower than those from residents of Kathmandu. As the epidemic in Kathmandu affected mostly the younger age groups, a comparison with the titres in children from Calcutta between 2 periods of time could reflect how rapidly A/England/42/72 virus was spreading in India and Nepal. In Calcutta, the GMT of A/England/42/72 antibodies rose from 111 to 162 while A/Hong Kong/1/68 antibodies rose from 108 to 138 over the same 3 months period. Cross-reactions were probably responsible for the latter increase (7). By the next spring there was evidence that the virus A/England/42/72 was in Nepal; antibody was found in the sera of children in 3 widely separated communities, but the antibody titres were low. However, during the following summer and autumn, the GMT of antibodies for A/England/42/72 virus rose from 224 to 435 while that for A/Hong Kong/1/68 virus rose only from 125 to 199. Thus, from July 1972 till January 1973 there was an epidemic of A/England/42/72 virus in Kathmandu. With time, the GMT exceeded 400 and the prevalence of antibodies among children 0-12 years of age reached 96%, whereas, earlier in Cal- cutta, the epidemic did not spread as rapidly (Fig. 1). Respiratory infections appeared to be a major reason for the hospitalization of children in Kath- mandu. The increase in the number of hospital admissions for all respiratory diseases except tuber- culosis in 1972 (Fig. 2) corresponded in time with the increased GMT and prevalence of A/England/ 42/72 virus (Fig. 1). An unknown proportion of the admissions was due to infection with this same virus. Moreover, there was an annual increase in admis- sions which coincided with the monsoon season (June till September). Similarly, an increased rate of isolation of most respiratory viruses was shown repeatedly to occur during the monsoon seasons in 477 478 V. 0. SOUSA ET AL. West Bengal, India (2). Thus, the epidemic in Kath- mandu, as in Europe (6), appeared to be short-lived with only a slight increase in the numbers of hospital admissions. Perhaps the high prevalence of antibody for A/Hong Kong/1/68 virus in the Kathmandu population had some protective value like that observed by Hoskins et al. (8) under more controlled conditions. Although the clinical data are limited, it is possible that the low prevalence and low GMT for A/Hong Kong/1/68 virus among Lang Tang villagers (Table 1) may have helped to produce more severe A/England/42/72 virus infections (1). In another study, HI antibodies for equine and avian strains of influenza were not found in human sera from Nepal. However, radial diffusion tests showed that antibodies for H3N2 antigens were present in cattle and goats in West Bengal and in water buffaloes, yaks, and cattle in Kathmandu. The direction of transmission between the species is unknown (13). ACKNOWLEDGEMENTS The authors gratefully acknowledge the assistance given by Dr L. Paudayl, Central Health Laboratory, Kathmandu; Dr P. L. Rajbhandari, Kanti Hospital, Kathmandu; and Dr K. Giri, Maternity Hospital, Kathmandu. This investigation was supported by Public Health Service Grant 5 R07AI 10048-13. RoSUMt PROPAGATION DES VIRUS GRIPPAUX A/ENGLAND/42/72 ET A/HONG KONG/1/68: ETUDE SEROLOGIQUE AU NEPAL ET A CALCUTTA (INDE) En aofit 1971, un mois apres le premier isolement du virus A/England/42/72(H3N2) en Inde, on a d6cel6 une s6roconversion a l'egard de ce virus chez un enfant de Calcutta. Au cours des 5 mois qui ont suivi, la moyenne g6om6trique des titres a subi une l6gere augmentation. Vers le milieu de 1972, la pr6sence du virus a 6t6 cons- tat6e au Nepal. A Katmandou, la moyenne g6om6trique des titres 6tait plus 6lev6e chez les enfants que chez les adultes. On a not6 une 6l6vation marqu6e de cette moyenne en 1972 et au d6but de 1973 avec, simultan6ment, un nombre accru d'admissions pour affections respiratoires dans les h6pitaux. Chez les habitants d'un village isole, Lang Tang, situ6 a 3 500 m d'altitude, la moyenne g6o- m6trique des titres et la pr6valence des infections A virus A/England/42/72 et A/Hong Kong/1/68(H3N2) 6taient inferieures de plus de la moiti6 aux valeurs relev6es a Katmandou. L'6pid6mie de Katmandou a et6 de courte dur6e. REFERENCES 1. CENTER for Disease Control, Morbid. Mort. wkly Rep., 22: 134 (1973). 2. CENTER for Medical Research and Training Report, 1971-72. The Johns Hopkins University, Baltimore. 3. CHAKRAVARTY, M. S. ET AL. Bull. Calcutta Sch. trop. Med., 18: 100-101 (1970). 4. COCKBURN, W. C. ET AL. Bull. 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