Review of varicella zoster seroepidemiology in India and South-east Asia

Authors


Lee Paediatric Department, National University Hospital, Lower Kent Ridge Road, Singapore

Abstract

Summary Varicella zoster virus (VZV) predominantly affects children in temperate countries, with near-universal seroconversion occurring by late childhood. However, in tropical regions, VZV infection is common in adolescents and adults. This review identifies age-related VZV seroprevalence patterns in a number of Asian countries which indicate that seroconversion in tropical countries occurs at a later age than in temperate countries. Seasonal and regional variations in acute disease within some Asian countries suggest that temperate climates might favour transmission of the varicella virus, with incidence peaking during cooler months and in cooler, more temperate regions. VZV infection is often more severe in adults than in children, suggesting that tropical countries may be at risk of greater morbidity and mortality as a result of later-age seroconversion. Susceptibility of pregnant women and their infants, and of people infected with HIV/AIDS is also cause for concern. Vaccination may be beneficial in reducing the impact of VZV in Asian populations.

Introduction

The varicella zoster virus (VZV) is a highly contagious agent responsible for chickenpox, a disease primarily affecting young children. Although varicella occurs worldwide, the epidemiology of the disease is markedly different in tropical and temperate countries. In temperate countries such as the US and the UK, the vast majority of the population have seroconverted to VZV by adolescence. Preblud (1986) found that at least 90% of Americans have encountered the virus by 15 years of age, while Muench et al. (1986 ) identified 100% seropositivity by 13 years of age in a study based in Seattle. Wharton (1996) found that only 6% of those aged 11–19 years were susceptible to VZV infection, and in a study of US Navy and Marine Corps recruits aged 15–29 years ( Struewing et al. 1993 ), only 6.7% were found to be seronegative to VZV. In other temperate countries the age-specific seroprevalence is similar. Fairley & Miller (1996) found in their UK study that > 90% of individuals had been infected by 15 years of age, and Eguiluz et al. (1987) demonstrated 80% seroprevalence to VZV by seven years of age in Spanish children. Seroprevalence is also high in Japanese children ( Taylor-Wiedeman et al. 1989 ), 83% of whom have seroconverted by 9 years of age.

Tropical countries, however, experience different age-related VZV seroprevalence patterns. Serological studies of immigrants from tropical countries ( Hastie 1980; Kjersem & Jepsen 1990) and of resident tropical populations ( Garnett et al. 1993 ) suggest that seroconversion generally occurs in late adolescence and adulthood. Further evidence that first contact occurs at a later average age in tropical countries was provided by Maretic & Cooray (1963), who found that acute infection in adults is more common in tropical countries than in temperate climates.

Studies from temperate countries show that varicella infection causes greater morbidity in adults than in children ( Guess et al. 1986 ; Baren et al. 1996 ), and greater mortality ( Preblud 1981; Preblud et al. 1984 ; Ventura 1997). Although the statistical evidence from tropical countries is sparse, a number of authors clearly believe that adulthood varicella is more severe than childhood varicella in tropical countries (White 1978; Lee & Tan 1995; Wharton 1996). Further investigation is necessary to clarify this important point.

Due to late seroconversion in tropical countries there is a relatively high proportion of women of child-bearing age who are susceptible to VZV during pregnancy. Infected mothers may pass the virus on to their unborn child, causing congenital varicella syndrome ( Preblud 1986; Enders et al. 1994 ). The possibility of postnatal disease also increases with adult disease.

Also susceptible to varicella are people with HIV/AIDS. Those who have not been in contact with VZV are regarded as particularly susceptible to primoinfection ( Sans et al. 1994 ), and these patients often become severely ill ( Peronee et al. 1990 ). Varicella zoster is one of the major viral pathogens reactivated in patients with HIV/AIDS ( Snoeck et al. 1994 ). Asian countries with a high prevalence of HIV/AIDS may have a greater morbidity and mortality associated with VZV.

Taken together, these factors indicate that the potential impact of VZV on public health in tropical countries is high, and that it has significant implications for vaccination programs in regions such as SE Asia. Vaccination may limit the morbidity and mortality associated with adult and neonatal disease and help to reduce the individual, social, and economic costs incurred by these countries as a result of their unique prevalence patterns.

The goal of this review is to confirm that several Asian countries experience VZV prevalence patterns typical of tropical countries. Data were obtained from published papers identified through a Medline search (1966–97) using the search items varicella, chickenpox, herpesvirus 3-human, Asia-South-eastern and India. Further studies were identified from the references of retrieved papers, while additional data were provided by members of the Steering Committee for the Prevention and Control of Infectious Diseases in Asia.

VZV prevalence in India and SE Asia

Seroprevalence studies conducted in a number of Asian countries have indicated that a significant proportion of the population remain susceptible to VZV infection well into adulthood. A summary of these studies is given in Table 1. Figure 1 contrasts age-related seroprevalence patterns in Asian countries with those in the temperate countries of the USA and the UK.

Table 1.   A summary of varicella seroprevalence studies in SE Asia Thumbnail image of
Figure 1.

 Age-related VZV seroprevalence in SE Asia, UK and USA. u Singapore ( Ooi et al. 1992 ); ▪ Malaysia ( Malik & Baharin 1995); ▵ India ( Venkitaraman et al. 1986 ); ▴ Philippines ( Barzaga et al. 1994 ); • UK ( Fairley & Miller 1996); ○ USA ( Muench et al. 1986 ).

Singapore

The incidence of varicella in Singapore has been increasing since the mid 1980s. While this may be partly due to better notification of disease ( WHO 1992), Chow et al. (1993 ) proposed that the upsurge could be attributed to the emergence of new VZV strains spreading among susceptible populations. A survey conducted between 1989 and1990 ( Ooi et al. 1992 ) revealed that less than half of the cohort had protective antibodies to VZV, confirming a low level of herd immunity. While the overall incidence of VZV has increased, age-specific data indicate a growing incidence among adolescents and adults. In a 1992 weekly Epidemiological Record, the WHO reported that while the highest incidence rate was seen in children aged 5–14 years from 1977 to 1982, this pattern changed in subsequent years, with the highest rate occurring in young adults aged 15–24 years, from 1985 to 1990. Seroprevalence data confirm the susceptibility of adolescents and adults to varicella. Ooi et al. (1992 ) found that only 41% of those aged 15 to 24 years had protective antibodies to VZV, and that > 90% seroprevalence was not reached until 35 years and over.

Malaysia

The prevalence pattern in Malaysia appears similar to that in Singapore, with relatively low seroconversion among children and > 90% seroconversion only in those over 30 years of age. Malik & Baharin (1995) found a progressive increase in seroprevalence from childhood to adulthood: 25.6% of the 1–5 years age group had seroconverted, compared with 47.2% of the 6–10 years age group and 50.8% of the 11–15 years age group. This rate increased to 70.0% in young adults aged 16–20 years, and to 79.0% in those 21–30 years of age, while more than 90% of those over 30 years possessed antibodies.

Philippines

A study conducted in the early 1990s in metropolitan Manila ( Barzaga et al. 1994 ) established that seroprevalence increased with age, progressing from 30% in children under 5 years of age to 57% in those <15 years of age. Prevalence continued to increase incrementally up to 30 years of age, with 92–95% prevalence found in those over the age of 30. In an earlier study, Nassar & Touma (1986) demonstrated that only 88% of adult, expatriate Filipino nurses working in Lebanon had seroconverted, compared with 97% of their Lebanese counterparts.

Thailand

In a seroprevalence study among university students ( Bhattarakosol et al. 1996 ), only 74% of those tested were found to possess anti-VZV antibodies, leading the authors to conclude that one in four young Thai adults remained susceptible to infection. Migasena et al. (1997 ) confirmed that many adolescents and young adults lacked protective antibodies, with seroprevalence reaching > 90% only in those over 30 years of age. In their survey of both immunocompromised and healthy children and young adults, Kositanont et al. (1985 ) concluded that 74% of children and 29% of young adults were susceptible and at high risk of varicella infection.

There is some evidence to suggest that the epidemiology of VZV infection in Thailand varies according to climate. In its 1995 Annual Epidemiological Surveillance Report, the Ministry of Health indicated that each year during the period 1989–95, more cases of chickenpox were reported in the north of the country than in other regions. In 1995, incidence per 100 000 population was approximately 100 in the north, compared to approximately 55 in the central region and 65 in the south. With its higher latitude, the northern climate is more characteristic of temperate countries and higher incidence here may suggest that transmission of the virus is favoured by this climate. However, it is also possible that other factors, such as increased crowding in homes in a cooler climate, may favour transmission because of larger inocula.

India

Venkitaraman et al. (1986 ) found a progressive increase in seroprevalence with age: 16% of children aged 1–4 years, compared with 54% of children aged 5–14 years, and 72% of those aged 15–25 years had been infected. Venkitaraman & John (1984) also found evidence of later-age seroconversion when only 29% of student nurses aged 17–20 years tested seropositive to VZV.

High infection rates in early adulthood and beyond suggest that much of the population do not encounter VZV during childhood. In one incidence study ( Sinha 1976), 63% of people in rural West Bengal with acute VZV infection were at least 15 years old, with a mean age of 23.4 years. In a second study ( Balraj & John 1994), 24% of people infected during an epidemic in rural Southern India were 16 or older.

It appears that there is some seasonal variation in acute cases of varicella in India. In a number of studies, incidence was found to peak during the cooler times of the year while dropping off in the summer months. In Kerala White (1978) found that most varicella cases are reported in January and February, the coolest months of the year. A surveillance report of the National Smallpox Eradication Programme ( Basu et al. 1979 ) showed a seasonal increase in cases of varicella in India during the months of March and April. Balraj & John (1994) also noted peak incidences at this time in their study of a varicella epidemic in southern India, with 190 of 292 cases occurring in the months of March and April. In a hospital-based study at Vellore, Venkitaraman & John (1984) noted that the incidence of varicella among hospital personnel peaked in March and September and dropped off in May, June and July, correlating these findings with low temperatures and humidity.

Discussion

The data presented in this review confirm the low prevalence of VZV among children in the tropical climates of Singapore, Thailand, Malaysia, the Philippines and India, compared to that in temperate countries. The relatively low rates of seroconversion found among children in these tropical countries may result from reduced VZV transmission. Garnett et al. (1993 ) proposed that the transmission potential of the VZV virus might be adversely affected by a combination of high ambient temperatures and humidity in tropical regions. There is indirect evidence to support this notion in the seasonal and regional variations in acute disease found within some SE Asian countries. Outbreaks of varicella appear to be more common in the cooler months of the year in India ( White 1978; Basu et al. 1979 ; Venkitaraman & John 1984; Balraj & John 1994) and in Thailand; incidence rates are highest in the temperate northern region of the country ( Ministry of Public Health 1995). Data from studies outside SE Asia also support the notion of reduced VZV transmission in hot, humid climates. For example, in their study of a Sri Lankan population, Maretic & Cooray (1963) found that the number of chickenpox admissions to a regional hospital in the cool, dry season more than doubled compared to the hot monsoon period. However, in other countries such as Singapore incidence does not seem to vary according to season ( WHO 1992).

An alternative explanation for the relatively low transmission of VZV in tropical countries is that the intense transmission of viruses among children in tropical countries creates competition among viruses for the same ‘soil’, leading to the postponement of some infectious diseases ( Bang 1975); however, it seems unlikely that varicella would be affected in this manner but not other viral infections transmitted by the same route. A third possibility is that closely related infections – such as herpes simplex virus – generate cross-immunity, as there is some serological evidence of cross-antigenicity between these viruses ( Edson et al. 1985 ).

Regardless of the mechanism by which VZV transmission is diminished in tropical countries, a case in support of VZV vaccination in India and SE Asian countries can be made on the basis of several factors: Indian and SE Asian seroprevalence studies suggest that a significant proportion of individuals are infected with VZV for the first time during adolescence and adulthood. VZV infection in adolescents and adults may be associated with higher morbidity and mortality than in children. In tropical countries, a high proportion of pregnant women and their infants are susceptible to VZV. VZV infection is frequent and can be severe in people infected with HIV/AIDS, and countries with a high incidence of HIV/AIDS may have a greater morbidity and mortality associated with VZV. Countries such as Singapore have experienced a progressive increase in the incidence of VZV since the mid-1980s. Although further investigation is needed to confirm the severity of VZV infection in adolescents and adults in tropical climates, it appears that vaccination against VZV could play an important role in improving public health in India and SE Asia.

Acknowledgements

The authors acknowledge financial assistance from SmithKline Beecham Biologicals for expenses associated with meetings of the Steering Committee.

Appendix

Appendix 1

Steering Committee for Prevention and Control of Infectious Diseases in Asia

Graham Cooksley, Clinical Research Centre, Royal Brisbane Hospital, Queensland, Australia; Veronica Chan, College of Public Health, Manila, Philippines; Ilina Isahak, Department of Medical Microbiology and Immunology, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia; Jacob John, Department of Clinical Virology and Immunology, Christian Medical College Hospital, Vellore,Tamil Nadu, India; Prayura Kunasol, Department of Communicable Disease Control, Ministry of Public Health, Nonthaburi, Thailand; Somsak Lolekha, Paediatric Department, Ramanthibodi Hospital, Bangkok, Thailand; Estrella Paje-Villar, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines; Yong Poovorawan, Paediatric Department, Chulalongkorn University, Bangkok, Thailand; Ng Han Seong, Department of Gastroenterology, Singapore General Hospital, Singapore; H Ali Sulaiman, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia

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