Secular trends of chickenpox among military population in Israel in relation to introduction of varicella zoster vaccine 1979–2010

Abstract

Chickenpox is a contagious disease caused by the varicella zoster virus. There is scarce data on long-term trends of chickenpox and its relation to vaccinations practices. We aimed to evaluate trends of chickenpox in a military population during the period 1979–2010 and to assess temporal associations in relation with the introduction of varicella zoster vaccine to the civilian population in Israel in 2000. The archives of the Epidemiology Section of the Israel Defense Forces, where chickenpox is a notifiable disease, were reviewed for all cases of chickenpox from January 1, 1979–December 31, 2010. Annual and monthly incidence rates were calculated and analyzed in relation to vaccine introduction. Between 1979–2000, incidence rates fluctuated around 10 cases per 10,000 soldiers without a clear trend. Since 2000 there has been a dramatic 10-fold decline in incidence, especially notable since 2008, from eight per 10,000 soldiers in 2000 to the lowest rate ever recorded, in 2009, of 0.57 cases per 10,000 soldiers. A seasonal sinusoidal pattern was clearly demonstrated, with rising incidence from November to May followed by a gradual decline to October. The results of this long-term study suggest that the rates of chickenpox in the military population have significantly declined since the introduction of the vaccine to the civilian population in Israel and almost disappeared completely since 2008 as the vaccine was included in the state-funded routine childhood immunization schedule. These findings underscore the need for a strong surveillance system and will aid in determing vaccination policies.

Keywords: :

• young adult
• vaccine
• vaccination policy
• epidemiology
• seasonality
• chickenpox
• varicella zoster virus

Introduction

Chickenpox is a contagious disease caused by the varicella zoster virus (VZV). The causative agent is a DNA alfa-herpesvirus that is a part of the Herpesviridae family.¹ This virus can cause two distinct clinical syndromes: varicella (chickenpox) and after endogenous reactivation, herpes zoster (shingles). Chickenpox is predominantly a childhood disease that is characterized by an incubation period of 10–21 d followed by a pruritic vesicular exanthema.¹ Systemic symptoms such as fever, headache, loss of appetite and malaise are frequent. The disease usually follows a benign course with complete resolution, however complications occur, albeit infrequently. The most frequent complication is secondary bacterial infection, mainly caused by group A β-hemolytic Streptococci or Staphylococcus aureus,² which can be invasive and life threatening. Other fatal complications include meningoencephlaitis and stroke caused by intracranial vasculitis.³

Chickenpox is highly communicable, with an attack rate ranging from 61–100% among susceptible individuals.⁴ The virus spreads through direct contact, droplet or airborne spread of vesicle fluid or respiratory secretions. The period of communicability for chickenpox cases is as long as 5 d, usually starting 1–2 d before onset of the rash, and continuing until all lesions are crusted. The combination of effective aerosol spread and a high attack rate is of great significance in crowded populations such as the military.⁵ The fact that the case-fataility rate from chickenpox among adults is 25 times greater than that in children, makes it an even more significant issue.⁶

A live attenuated VZV vaccine was first developed in 1975 in Japan.⁷ The vaccine was licensed and made available in Israel in 2000, where it was subsidized for children (but not soldiers) by supplementary health insurance plans, and became widely popular, only for private purchase. The VZV vaccine was eventually included in the state-funded routine childhood immunization schedule in September 2008. The current schedule includes two doses of live attenuated VZV vaccine to be given with measles-mumps-rubella vaccine at age 1 and 6–7 y.⁸ We have previously reported declining seroprevalence to varicella among recruits to the Israeli Defense Forces (IDF) in 2003 compared with 1992.⁹ Data on long-term secular and seasonal trends of chickenpox in adult populations with relation to the impact of childhood vaccination are scarce, as in most countries the disease in either not a notifiable disease, or has only recently been added to the mandatory reporting list. Based on this background, we analyzed chickenpox surveillance data in the IDF, where the disease is mandatorily reported since 1979. The primary objective of this study was to evaluate secular trends of chickenpox in the military population during 1979–2010 relative to the introduction of VZV vaccine. Our secondary objective was to assess seasonal trends in chickenpox morbidity.

Results

Military conscipts aged 18–21 comprised 78% of the study population (male 53%, female 25%) and career personnel aged 22–45 represented 22% (male 19%, female 3%).

Annual epidemiology

The secular trends in annual incidence rates can be crudely divided into three periods (Fig. 1). The period between 1978 and 2000 was characterized by relatively high incidence rates that fluctuated around 10 cases per 10,000. Rates declined significantly (more notable after 2005) during 2001–2008 period to annual rates around 2–7 cases per 10,000. After 2008, the disease disappeared almost completely. Overall, we observed a dramatic, more than 10-fold decline in annual incidence from eight per 10,000 to an all time low of 0.57 cases per 10,000 in 2009.

Figure 1. Varicella zoster in the Israel Defense Forces: Annual incidence rates per 10,000 soldiers, 1979–2010. Changes in VZV vaccination schedule are marked in arrows.

Seasonal epidemiology

The average monthly seasonal incidence rate of chickenpox in the military population is presented in Figure 2. The average monthly rates varied from a low of 0.20 cases per 10,000 in October and November to a high of 1.20 cases per 10,000 in May. A clear sinudoidal seasonal pattern was observed as rates increased steadily between November and May and decreased steadily until October.

Figure 2. Varicella zoster in the Israel Defense Force: average monthly incidence rates per 10,000 soldiers, 1979–2010.

Discussion

The results of this long-term epidemiologic study suggest that the rates of chickenpox in the IDF have significantly declined since the introduction of the vaccine to the civilian population in Israel in 2000. A further pronounced decline has been observed since 2005 (the first year of vaccine subsidization) at which time the vaccine uptake increased significantly with an annual number of vaccinees that has grown 2.6-fold as compared with previous year.¹⁰ However, this marked decrease cannot be definitely related to the increased vaccine coverage and may reflect a normal secular trend of varicella disease. Following the introduction of the routine childhood vaccination in September 2008, there was almost a complete disappearance of the disease. Prior to the introduction of the vaccine, we observed a seasonal pattern of rising incidence between November and May, followed by a gradual decline until October.

The epidemiology of chickenpox differs in temperate and tropical climates.¹¹ In temperate climates, the disease is more frequent among children whereas in tropical climates, adults are at higher risk. The disease is characterized by year-to-year variation in incidence, and epidemics occur at intervals of 2–5 y.^12,13 The annual epidemiology of chickenpox has changed considerably since the introduction of the vaccine. Active surveillance performed in the United States showed a dramatic decline in disease incidence in all age groups.¹⁴ This fact has special importance for our population of military personnel, as chickenpox is a more severe disease among adults: the course of the disease is protracted, the risk of severe complications is greater and mortality rates are higher. It has been estimated that the risk for death from chickenpox in adults is 23–29 times higher than that in children.¹⁵ A seroepidemiological study performed in Israel between the years 2000–2001 discovered varying seropositivity rates across age categories. While the overall rate of seropositives was 90.2%, this proportion increased with age from 68.9% at age 4 to 96.6% at age 12.¹⁶ Another seroprevalence study in Israel conducted in 2003 among 536 military recruits at age 18 y found a seroprevalence of 94.6%, which was significantly lower than the percentage observed in the same population in 1992 (98.4%).⁹ As stated above, the vaccine was licensed and made available in Israel in 2000. The vaccine was subsidized for children (but not soldiers) by supplementary health insurance plans, and became more and more popular, especially after 2005, however, only for private purchase. The VZV vaccine was eventually included in the state-funded routine childhood immunization schedule in September 2008. To the best of our knowledge, vaccination of our population prior to or during military service was rare, as the vaccine was marketed mainly for children. As was the case following the introduction of other vaccines among infants, such as hepatitis A and measles-mumps-rubella, a significant decline in rates among adults became apparent shortly after vaccine introduction.^17,18 The probable explanation for this observation is that vaccination of infants plays an important role in diminishing the viral reservoir, thus disrupting the chains of infections. The impressive magnitude of decline underscores the benefits for adults of childhood varicella vaccination. It is important to note that introduction to routine childhood vaccination after 2008 was related with almost complete disappearance, while wide use during earlier periods was associated only with a significant reduction in incidence. This is an important finding supporting routine childhood varicella vaccination. Such evidence is especially important in light of concerns raised regarding the effect of childhood vaccination on shingles incidence in the elderly.¹⁹

The decline in incidence rates found in this study should not be regarded as a sign that chickenpox is no longer a threat to adults in our population. Indeed, the decreasing chickenpox seroprevalence previously found among IDF recruits indicates that the adult population is more susceptible now than in the past, at least until cohorts of those vaccinated in childhood reach adulthood. Several studies indicate that humoral immunity persists for many years after immunization in healthy children, particularly when circulation of wild-type VZV continues to oocur.²⁰ However, as learned from mumps and other pathogens, surveillance and sero-prevalence efforts should be continued and sometimes even extended for vaccinated populations, as waning immunity, decrease in natural exposure, immigration or other reasons may lead to unexpected breakthrough illness in the future.^21,22 Indeed, the civilian notification system in Israel was changed in 2011 as chickenpox became indvidually reported to the Ministry of Health. The overall incidence (missing first 2 wks of 2011 and last month of 2012) for 2011 and 2012 were 1 case per 10,000 and 1.7 cases per 10,000, respectively.²³

Chickenpox is highly contagious and tends to appear in clusters, thereby placing military populations at greater risk of disease. Therefore, the IDF Medical Corps continues to perform surveillance and control efforts with an increased vigilance. Each case of chickenpox is isolated until vesicles become dry and crusted. Post-exposure prophylaxis with VZV vaccine is considered for susceptible individuals following exposure to chickenpox, depending on the timing of notification. VZV immunoglobulin is considered for high-risk persons who were in close contact with cases, a rare scenario in our population.

There are some possible limitations of this study. Physician-reported cases of chickenpox are not necessarily laboratory-confirmed, as clinical diagnosis is often sufficient for case management. However, it is unlikely that the rate of laboratory confirmation changed over time, so this would not affect the validity of the analysis. Another possible bias is missed or non-reported cases of chickenpox in soldiers who did not seek medical care or who were treated by a non-military physician while on leave. However, since the signs and symptoms of clinical chickenpox are apparent and not easily ignored, and since only a military physician can order sick leave from service, we can safely assume that were seen by a military physician and that only a marginal proportion of cases went unseen.

We found that the gradual increase in vaccine uptake starting in 2000, which culminated in routine childhood vaccination in 2008, has resulted in a dramatic 10-fold reduction in the occurrence of chickenpox among our population of young adults, leading almost to complete disapperance. This finding strengthens the need for a strong surveillance system and will aid in determing VZV vaccination policies, giving evidence to their positive impact on unvaccinated adult population.

Patients and Methods

The archives of the IDF Epidemiology Section were carefully reviewed for all documented cases of chickenpox from January 1, 1979 (start of mandatory notification)–December 31, 2010 (latest available data). Our analysis covered all compulsory and career IDF personnel. Since military service is mandatory in Israel for males and females, the study population represents a sample of the young adult population in Israel, excluding ultra-orthodox Jews and Israeli Arabs as well as people with severe chronic illnesses who are largely exempted from service, and are thus under-represented in the study population. Reserve personnel were excluded from the study. Geographically, the state of Israel is located at a latitude of 29°–33° north and is characterized by a subtropical climate. The rainy season extends from October to early May, and rainfall peaks in December through February.

The diagnosis of chickenpox in the IDF is based on the clinical presentation, relevant epidemiologic data and when there is a specific clinical or epidemiological necessity, confirmation by laboratory tests. For the present study, cases were identified using military physician-reported notification forms.

The civilian reporting system in Israel is separate from that of the military, and notification is mandatory only for the occurrence of at least two cases linked to a single source. Therefore, the overall rates of the civilian sector are unknown.

Statistical Analysis

The annual rates of chickenpox cases were calculated by dividing the number of cases reported through the military reporting systems each year by the respective mean annual population size. The average monthly rates of chickenpox cases were calculated by dividing the number of cases each month by the mean annual population for the corresponding year and averaging like months over the study period. All rates are presented per 10,000 population. All statistical tests were performed with WINPEPI Computer Programs for Epidemiologists (Abramson, J.H. WINPEPI updated: computer programs for epidemiologists and their teaching potential. Epidemiologic Perspectives and Innovations 2011, 8:1).

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.