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Original Articles Indian Pediatrics 2000;37: 714-719 |
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AGE RELATED SEROPREVALENCE OF ANTIBODIES TO VARICELLA IN INDIA |
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Key words: Varicella Zoster virus, Seroepidemiology. Varicella is a highly infectious exan-thematous disease caused by Varicella Zoster VSirus (VZV) with a secondary attack rate of 85-90%. It is considered to be a benign disease in childhood, lasting for 1-2 weeks with a typical papulo-vesicular rash, mild-moderate fever and occasionally constitutional symp-toms. Varicella has world-wide distribution with an annual incidence estimated to be equal to the birth cohort(1). However, there is considerable interest in the disease due to epidemiological variations between geographic locations, espe-cially between temperate and tropical regions of the world. In temperate countries, it is consi-dered to be a childhood disease with almost universal seroconversion by early adolscence. Nearly 100% seropositivity to VZV has been documented by 11-13 years in USA(2,3). Numerous reports point to a different age distribution pattern of VZV infection in tropical countries with greater morbidity in adults(4). Studies from South East Asia, namely, Singapore(5), Thailand(6,7), Malaysia(8) and Philippines(9) have reported the same. How-ever, limited data is available on the prevalence of antibodies to varicella in India. Reports from South India(10,11) have revealed that close to 30% of adolescents above 15 years are susceptible to VZV infection. With the availability of vaccines against varicella, recently there has been renewed interest in the epidemiology of this disease. This study was therefore conducted to determine the age-specific prevalence of VZV antibodies in the Indian Population.
This study was a cross-sectional multi-centric study conducted from September 1998 to December 1998, according to The Declara-tion of Helsinki and Good Clinical Practice guidelines. The study population consisted of 1609 healthy male and female volunteers from 0 to 40 years. They were recruited in 4 metropolitan cities of India, namely, Calcutta (patients recruited from hospital outpatient clinic), Lucknow (subjects recruited among walk-in patients to a diagnostic laboratory who consented to give a blood sample, orphanage and factory workers), Mumbai (recruitment of subjects from hospital outpatient clinics) and Bangalore (subjects recruited from outpatient clinics and walk-in patients to a diagnostic laboratory who consented to give a blood sample). A written informed consent was taken from the subjects or the parents/guardians of the subjects prior to enrolment into the study. Subjects were medically examined, checked for inclusion and exclusion criteria, a questionnaire was completed with background socio-economic strata in the form of permanent address, type of residence chawl/apartment/bungalow; monthly family income; and past and family history of Varicella. All the subjects enrolled were healthy volunteers residing permanently in the area. The exclusion criteria were: acute illness, fever >38.5°C, recent administration of immuno-globulins, blood products or immuno-suppressive therapy and suspected or confirmed immuno-suppressive conditions. Serum was separated by centri-fugation at 1500 rpm for 5 minutes immediately after blood sample was collected. Serum samples from all the centers were transported to Mumbai under strict cold chain conditions and then stored at –20°C until tested at Speciality Ranbaxy Laboratories, Mumbai. Enzyme Linked Immunosorbent Assay (ELISA) was used to measure VZV specific IgG qualitatively. We used a commercial kit (Anti VZV IgG-Enzygnost, Behringwerke, Marburg, Germany) according to manufac-turers specification. Delta absorbance readings of >0.2 were taken as positive to indicate immunity to VZV infection; values <0.1 were considered negative and indicated susceptibility to VZV infection. Values between 0.1 and 0.2 obtained twice on the same samples were classified as equivocal.
A total of 1609 volunteers were enrolled into the study. Of these 56 subjects were excluded because of hemolysed blood samples and 7 were excluded because they were more than 40 years of age. This left a total of 1546 subjects for final analysis. The demographic characteristics of the population under study are listed in Table I. The overall seroprevalence rate was 68.2%. The seroprevalence rate of VZV antibodies increased with age (Table II ) from 29% in 1-5 years group to 71.2% at age 11-15 years and 91.1% at age 31-40. We did not find a link between socio-economic stratification and anti-VZV seroprevalence. Table I__Demographic Characteristics
Table II__Age Related Seroprevalence of Varicella Antibodies
N = Number of subjects in each age group; % SP = % Seropositive, 95% CI = 95% Confidence interval.
The different epidemiology of primary vari-cella infection between tropical and temperate countries is a known fact; VZV sero-positivity is reached earlier in temperate countries and later in life in tropical countries. Our results reveal that prevalence of antibodies to varicella gradually increases through childhood, adole-scence and adulthood. An overall seropositivity rate of >70% was reached between the ages of 11-15 years which increased to nearly 90% at the age of 30 years. This is in contrast to tem-perate countries, where studies have reported near universal seropositivity by early adole-scence. For the USA reports mention 100% seropositivity by the age of 13 years(2) or only 6% susceptible 11 to 19 year olds(3). Similar inferences are forthcoming from epidemio-logical and serological studies in other tem-perate countries. In the UK >90% of individuals were infected by the age of 15 years(12); there was 80% seropositivity by the age of 7 years in Spanish children(13) and 83% sero- conversion by the age of 9 years in Japanese children(14). Our results are comparable to those reported for other tropical countries (Table III ). In our study Varicella susceptibility extended even into the 30-40 years of age group. In Singapore investigators found that only 41% of those aged 15-24 years had protective antibodies and >90% seroprevalence was not reached until 35 years of age(5). In Thailand, two groups reported that many adolescents and young adults lack protective antibodies, with seropre-valence reaching >90% only in those above 30 years(6,7). Similar results have been reported from Malaysia and the Philippines with only 50-58% seroconversion below 15 years of age(8,9). An earlier study from Vellore, India, showed an age related seropositivity rate of 54% in the age group 5-14 years and of 72% in the age group 15-25 years, with a median age of acquiring the infection of 12.5 years(10). Among student nurses in Vellore (aged 17-20) only 29% tested seropositive to anti-VZV(11). It is postulated that high ambient temperature and humidity in the tropics decreases VZV transmission by inactivating the virus in the cutaneous lesions. Alternatively, it is possible that because of high prevalence of certain other childhood viruses in tropical coun-tries, there is interference with the transmission of VZV and the age of varicella infection is postponed(15). In conclusion, VZV seroprevalence in-creases with age in the Indian population and a significant proportion of adolescents are still susceptible to varicella infection. In older sub-jects the disease is more severe and prolonged and has a 15-25 times higher mortality than in children(16). Consequently, any varicella vaccination strategy in Indian population should include susceptible adolescents along with children. Contributors: MRL, AA, SDS, MSC, AVRP, RCS and NS conducted the study in respective regional centers; SK co-ordinated the study and drafted the manuscript; HB was responsible for design and conduct of the study and drafting the manuscript; and JW helped in designing, conducting and co-ordinating the study and drafting the paper; he will act as the guarantor.Funding: SmithKline Beecham Biologicals, Rixensort, Belgium. Competing interests: JW, HB and SK were employees of SmithKline Beecham Biologicals at the time the study was conducted. Smithkline Beecham Biologicals market Varicella vaccine.
Table III__Age
Related Seroprevalence (%) of Varicella Antibodies in Some South
East Asian Countries
We are grateful to Ms. Jayaprabha at CDMCI, Bangalore for statistical analysis and Ms. Jeroze Dalal, Clinical Operations Manager and Mala Srivastava, Clinical Research Associate, SmithKline Beecham, Bangalore for the help rendered in monitoring and ensuring smooth conduct of the study.
1. Varicella Zoster Infections. In: Red Book; Report of the Committee on Infectious Diseases, 24th edn. Ed. Peter G. American Academy of Pediatrics, Elk Grove Village Illinois, 1997; pp 573-585. 2. Munech R, Nassim C, Nikku S. Sero-epidemiology of varicella. J Infect Dis 1986; 153: 153-155. 3. Wharton M. The epidemiology of varicella zoster virus infections. Infect Dis Clin North Ame 1996; 10: 571-581. 4. Flisser A, Quintanilla GF, Magos C, Conyer TR. The last 10 years: Changing epidemiology of varicella virus. Virus Life 1997; 16: 12-15. 5. Ooi PL, Goh K-T, Doraisingham S, Ling AE. Prevalence of varicella zoster virus infection in Singapore. Southeast Asian J Trop Med Public Health 1992; 23: 22-25. 6. Bhattaraskosol P, Chantarabul S, Pittayathikum K, Mung-Mee V, Punnarugsa V. Prevalence of anti-varicella zoster IgG antibodies in post graduate students. Asia Pacific J Allergy Immunol 1996; 14: 129-131. 7. Migasena S, Simasthien S, Desakorn V, Phonrat B, Suntharasamai P, Pitisuttitham P, et al. Seroprevalance of varicella zoster virus anti-bodies in Thailand. Int J Infect Dis Children 1997; 2: 26-30. 8. Khairnullah NS, Wang CK, Koh CG. Pre-valence of varicella zoster virus antibodies in the University Hospital, Kuala Lumpur, Malaysia. Proceedings of 5th Western Pacific Congress on Chemotherapy and Infections Diseases, 1996; p 184. 9. Barzaga NG, Roxas JR, Florese RH. Varicella zoster virus prevalence in Metro Manila, Philippines. J Am Med Assoc (SEAsia) 1994; 274: S633-S635. 10. Venkitaraman AR, John J. Measurement of antibodies to varicella zoster virus in tropical population by enzyme linked immunosorbant assay. J Clin Microbiol 1984; 20: 582- 583. 11. Venkitaraman AR, John J. The epidemiology of varicella in staff and students of a hospital in the tropics. Int J Epidemiol 1984; 13: 502-505. 12. Fairly CK, Miller E. Varicella zoster virus epidemiology–A changing scene. J Infect Dis 1996; 174 (Suppl): S314-S319. 13. Eguliz GC, Trallero EP, Garcia Arenzang JM. Seroepidemiology of varicella zoster in children in Spain. J Infect Dis 1987; 156: 851. 14. Taylor-Weidmen J, Yamashita K, Miyamura K, Yamazaki S. Varicella zoster virus prevalence in Japan: No significant change in the decade. Japenese J Med Sci and Biology 1989; 42: 1-11. 15. Lee BW. Review of
varicella zoster epidemio-logy in India and South East Asia. Trop
Med Int Health 1998; 11: 886-903. |
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