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.
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.
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.
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.
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.
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.