Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study

Varicella, or chickenpox, is an infectious disease caused by the ubiquitous varicella-zoster virus (VZV). It used to be considered a relatively benign communicable disease of childhood [1]. However, serious complications can occur, including secondary bacterial skin and soft tissue infections, cerebellitis, encephalitis, pneumonia and coagulopathy [1, 2]. Hospitalization rates due to chickenpox are considerably high in developed countries, especially among children. The reported chickenpox complication rates range from 40.7% to 83.3% of children hospitalized with the condition in various studies [3‐5]. Furthermore, a mortality rate of 2-3 per 100,000 affected persons has been reported [1]. Therefore, varicella remains an important public health issue worldwide. Despite the availability of a safe and effective varicella vaccine since 1986, there is no recommendation for universal vaccination against varicella in Hong Kong [6‐8].

It has been reported that the epidemiology of varicella appears to vary among different geographic regions, climatic belts, population densities, and degrees of socioeconomic development [9‐11]. A number of studies have been conducted to investigate the possible association between the occurrence of varicella infection and various environmental factors, such as temperature, rainfall and humidity. Wu et al has shown that season and temperature are significantly related to varicella incidence in Taiwan [12]. Another study performed by Kokaze et al demonstrated that the annual temperature variation affected the seasonal variations of varicella incidence in Japan [13]. In Hong Kong, the rates and characteristics of chickenpox in children have not been clearly described.

The objective of this study was to investigate the local epidemiology and seasonal trend of varicella in hospitalized children in Hong Kong. Furthermore, the possible underlying association between varicella incidence and various climatic factors was also explored using time series methodology.

A retrospective study was conducted to analyse the clinical information of all children and adolescents aged below 18 years who were hospitalized for varicella at Princess Margaret Hospital, a tertiary referral hospital for paediatric infectious diseases, between 1 January 2004 and 31 December 2008. Cases were identified by reviewing hospital discharge records retrieved using the relevant International Classification of Diseases 9^th Edition (ICD-9) principal or secondary discharge diagnostic codes for varicella or chickenpox, as in other epidemiological studies [2, 3]. The inclusion criteria were: children aged below eighteen years; principal or secondary discharge diagnostic codes being either varicella or chickenpox; and patients being admitted for varicella to Princess Margaret Hospital during the period from 1 January 2004 to 31 December 2008. All hospital admissions, not limited to emergency admissions, were included for time series analysis. Cases of herpes zoster were excluded.

Hospital discharge records for all the cases fulfilling the inclusion criteria were retrieved. Relevant demographic, clinical and admission data were extracted from the hospital discharge records. Relevant demographic data included age and gender of the patients. Relevant clinical data included the presence or absence of associated complications and the type of complications of the patients. Important admission data included the month and year of hospital admission and the length of hospitalization. The diagnosis of encephalitis was based on clinical features (decreased consciousness and seizure or focal neurologic deficit), cerebrospinal fluid pleocytosis, electroencephalographic changes and neuroimaging findings [14]. The diagnosis of cerebellitis was based on clinical findings of ataxia and other cerebellar signs. The diagnosis of pneumonia is based on clinical, laboratory and radiological features [14]. The diagnosis of skin and soft tissue infections was based on clinical signs (cellulitis, skin abscess, myositis or necrotizing fasciitis), and surgical scarlet fever was based on clinical features (sandpaper-like erythema, strawberry tongue and Pastia's lines).

Meteorological data including monthly mean air temperature, monthly mean relative humidity and monthly total rainfall were obtained from the overall monthly reports of meteorological observations during the study period from the website of Hong Kong Observatory [15].

This is the first time series study exploring the possible assoication between paediatric varicella hospitalization and weather factors in Hong Kong. Our dataset is relevant because the involved hospital, Princess Margaret Hospital, is a tertiary referral hospital for paediatric infectious diseases. The involved hospital received not only patients in its locality, but also patients transferred from other public hospitals. Age-specific hospitalization rates vary between studies and generally peak in children aged 1-4 years as they did in the present study [3, 4, 18]. The complication rates reported in literature among children hospitalized for varicella infection range from 40.7% to 83.3% [3‐5]. In the present study, the complication rate was 47%. The distribution of different complications in this study was similar to that reported in other paediatric series, with skin and neurological complications occurring most commonly [4, 5, 14, 18].

Time series analysis has been used extensively to study the effect of weather factors on various infectious diseases [19‐23]. In the current study, Poisson regression with generalized estimating equations (GEE) was used to examine the potential effect of various weather factors on the incidence of chickenpox in paediatric patients hospitalized in a tertiary hospital in Hong Kong during the period of 2004 to 2008. Monthly mean relative humidity, especially in cool seasons, was found to be inversely correlated with the number of varicella cases in the same month.

It has been suggested that the transmission potential of the VZV virus might be adversely affected by a combination of high ambient temperatures and humidity in tropical regions [24]. A review of data from Southeast Asia showed that the peak incidence of varicella infection occurred during cooler months and in cooler, more temperate regions [25]. Outbreaks of varicella appear to be more common in the cooler months of the year in India and in Thailand; incidence rates are highest in the temperate northern region of the country [26‐28]. Data from studies outside Southeast Asia also support the notion of reduced VZV transmission in hot, humid climates [29]. For example, Maretic and Cooray 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 in their study of a Sri Lankan population [30]. Lolekha et al reported that the age-adjusted seroprevalence was significantly higher in the cooler than in the warmer regions in Thailand [31]. Wu et al has shown that season and temperature are significantly related to varicella incidence in Taiwan [12]. Another study performed by Kokaze et al demonstrated that the annual temperature variation affected the seasonal variations of varicella incidence in Japan [13].

Varicella patients excreted the virus from their respiratory tract or vesicles and disseminated the virus to the environment via an aerosol route [32]. VZV can be transmitted via airborne spread [33]. However, the exact mechanism for the potential association between relative humidity and varicella incidence and transmission is not known. One could hypothesize that with a lower relative humidity, the density of air particles would be lower and hence the VZV could have stayed longer in the air during its airborne transmission to a long distance. Another possibility could be that in a dry environment with more dry skin, the patients with chickenpox could suffer from excessive itchiness where more skin scratching would facilitate more viral spread to the environment. In addition, the more common respiratory symptoms such as cough and sputum production in the dry season could enhance the aerosol spread of the VZV. However, all these hypotheses warrant further studies to explore the mechanism underlying the association between relative humidity and varicella infection.

Our study may have some limitations. First, it is based on hospitalization discharge records, and therefore children with mild disease and complications may have been excluded due to the absence of hospitalization. The potential climatic association with varicella might have been dampened by this selective sample. Second, using discharge diagnoses codes for data collection might result in errors due to the possibility of miscoding. But studies investigating the accuracy of ICD-9 codes for various diseases in different countries suggested that this is a useful tool for epidemiological studies [4, 34, 35]. In addition, chickenpox is considered to be a easily recognisable disease [2, 36]. Third, as the weather fluctuation in Hong Kong is relatively small, the potential effect of weather factors might have been better captured by decreasing the data interval, for instance, a weekly or daily basis, or increasing the study period. It should be acknowledged that varicella transmission is multifactorial [37‐39]. Apart from potential weather attributes, other environmental and host factors may also affect the incidence and transmission of the disease. Further studies to incorporate more variables such as age, geographic location, and frequency of contact expressed by population density and school contact patterns are warranted in the future.

In conclusion, varicella is a disease that can provoke serious complications and long hospital stays, even in healthy children. Lower relative humidity, especially in the cool seasons, is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong.

The authors declare that they have no competing interests.