• View in gallery

    Overall HAV seroprevalence rate by age group (χ2 test for the trend P < 0.001).

  • 1

    WHO, 2000. Hepatitis A vaccines, WHO position paper. Wkly Epidemiol Rec 75 :38–44.

  • 2

    Battegay M, Gust ID, Feinstone SM, 1995. Hepatitis A virus. Mandell JL, Benett JE, eds. Principles and Practice of Infectious Disease. New York: Churchill Livingstone 1636–1656.

  • 3

    Hadler SC, 1991. Global impact of hepatitis A virus infection changing patterns. Hollinger FB, Lemon SM, Margolis H, eds. Viral Hepatitis and Liver Disease. Baltimore: Williams & Wilkins, 14–20

  • 4

    Gust ID, 1992. Epidemiological patterns of hepatitis A in different parts of the world. Vaccine 10 :S56–S58.

  • 5

    Gay NJ, Morgan-Capner P, Wright J, Farrington CP, Miller E, 1994. Age-specific antibody prevalence to hepatitis A in England: implications for disease control. Epidemiol Infect 113 :113–120.

    • Search Google Scholar
    • Export Citation
  • 6

    Werzbeger A, Mensch B, Kuter B, Brown L, Lewis J, Sitrin R, Miller W, Shouval D, Wiens B, Calandra G, 1992. A controlled trial of formalin-inactivated hepatitis A vaccine in healthy children. N Engl J Med 327 :453–457.

    • Search Google Scholar
    • Export Citation
  • 7

    Innis BL, Snitbhan R, Kunasol P, Laorakpongse T, Poopatanakool W, Kozik CA, Suntayakorn S, Suknuntapong T, Safary A, Tang DB, Boslego JW, 1994. Protection against hepatitis A by an inactivated vaccine. JAMA 271 :1328–1334.

    • Search Google Scholar
    • Export Citation
  • 8

    Andre FE, D’Hondt E, Delem A, Safary A, 1992. Clinical assessment of the safety and efficacy of an inactivated hepatitis A vaccine: rationale and summary of findings. Vaccine 10 (Suppl 1):S160–S168.

    • Search Google Scholar
    • Export Citation
  • 9

    Andre F, Van Damme P, Safary A, Banatvala J, 2000. Inactivated hepatitis A vaccine: immunogenicity, efficacy, safety and review of official recommendations for use. Expert Rev Vaccines 1 :9–23.

    • Search Google Scholar
    • Export Citation
  • 10

    Lebanese decree no 8733. Fixing the minimum wages of the employees and workers as well as the increase of the cost of living. Lebanese Official Gazette (in Arabic: Jaride Al Rasmiye) Lebanon, Published on 8 July 1996.

  • 11

    Shammaa MH, Abu-Samra S, Salameh V, Nassar NT, 1982. The significance of anti-HAV in different population sectors in Lebanon: a comparative seroepidemiologic study. Int J Epidemiol 11 :406–409.

    • Search Google Scholar
    • Export Citation
  • 12

    Kalaajieh W, Rima A, Dennaoui M, Al Khodayry R, 2000. Seroprevalence of hepatitis A antibodies in Lebanese children. Med Mal Infect 30 :757–761.

    • Search Google Scholar
    • Export Citation
  • 13

    Tanaka J, 2000. Hepatitis A shifting epidemiology in Latin America. Vaccine 18 (Suppl 1):S57–S60.

  • 14

    Poovorawan Y, Theamboonlers A, Sinlaparatsamee S, Chaiear K, Siraprapasiri T, Khwanjaipanich S, Owatanapanich S, Hirsch P, 2000. Increasing susceptibility to HAV among members of the young generation in Thailand. Asian Pac J Allergy Immunol 18 :249–253.

    • Search Google Scholar
    • Export Citation
  • 15

    Tufenkeji H, 2000. Hepatitis A shifting epidemiology in the Middle East and Africa. Vaccine 18 (Suppl 1):S65–S67.

  • 16

    Green MS, Aharonowitz G, Shohat T, Levine R, Anis E, Slater PE, 2001. The changing epidemiology of viral hepatitis A in Israel. Isr Med Assoc J 3 :347–351.

    • Search Google Scholar
    • Export Citation
  • 17

    Halliday ML, Kang LY, Zhou TK, Hu MD, Pan QC, Fu TY, Huang YS, Hu SL, 1991. An epidemic of hepatitis A attributable to the ingestion of raw clams in Shanghai, China. J Infect Dis 164 :852–859.

    • Search Google Scholar
    • Export Citation
  • 18

    WHO, 1995. Public health control of hepatitis A: memorandum from a WHO meeting. Bull WHO 73 :15–20.

  • 19

    McMahon BJ, Beller M, Williams J, Schloss M, Tanttila H, Bulkow L, 1996. A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine. Arch Pediatr Adolesc Med 150 :733–739.

    • Search Google Scholar
    • Export Citation
  • 20

    Salleras L, Bruguera M, Buti M, Domingez A, 2000. Prospects for vaccination against hepatitis A and B in Catalonia (Spain). Vaccine 18 (Suppl 1):S80–S82.

    • Search Google Scholar
    • Export Citation
  • 21

    Germinario C, Lopalco PL, Chicanna M, Da Villa G, 2000. From hepatitis B to hepatitis A and B prevention: the Puglia (Italy) experience. Vaccine 18 (Suppl 1):S83–S85.

    • Search Google Scholar
    • Export Citation
  • 22

    Fishman RH, 1998. Hepatitis A vaccine for Israeli children. Lancet 352 :88846.

  • 23

    Dominguez A, Salleras L, Carmona G, Batalla J, 2003. Effectiveness of a mass hepatitis A vaccination program in pre-adolescents. Vaccine 21 :698–701.

    • Search Google Scholar
    • Export Citation
  • 24

    Demicheli V, Carniglia E, Fucci S, 2003. The use of hepatitis a vaccination in Italy: an economic evaluation. Vaccine 21 :2250–2257.

  • 25

    Ginsber GM, Slater PE, Shouval D, 2001. Cost-benefit analysis of a nationwide infant immunization programme against hepatitis A in an area of intermediate endemicity. J Hepatol 34 :92–99.

    • Search Google Scholar
    • Export Citation

 

 

 

 

HEPATITIS A IN LEBANON: A CHANGING EPIDEMIOLOGICAL PATTERN

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  • 1 St. Georges Hospital, Beirut, Lebanon; Hotel Dieu De France Hospital, Beirut, Lebanon; Hammoud Hospital, Saida, Lebanon; Nini Hospital, Tripoli, Lebanon; GlaxoSmithKline Biologicals, Rixensart, Belgium

In this multicenter study in Lebanon, hepatitis A virus (HAV) seroprevalence rates were surveyed by age, gender, and socioeconomic factors. Blood samples collected from 606 subjects aged 1 to 30 years were analyzed for anti-HAV IgG. Age was the most important factor influencing HAV seroprevalence. HAV seroprevalence rates in the current study were about 78% in the ≥ 21 years age group, 28% in the 6–10 years age group, and 11% in the 1–5 years age group as compared with 97.7% in adults, 85% in children aged 6–12 years, and 40% in children aged 1 to 5 years in previous studies, demonstrating a shift in HAV seroprevalence from the younger to the higher age groups. In light of the severity of the disease in adults and availability of safe and effective vaccines against HAV infection, introduction of HAV vaccination into the national immunization schedule of Lebanon should be considered.

INTRODUCTION

Hepatitis A virus (HAV) is a major cause of disease throughout the world, with an estimated 1.5 million cases annually.1 Although infection by the hepatitis A virus is often asymptomatic or accompanied by mild, nonspecific illness in young children, in adults the disease can be severe. Fatal acute liver failure is a well-known complication of HAV infection but fortunately uncommon. The prevalence of HAV is very closely related to the socioeconomic status of the population and may vary within the same country according to changes in hygienic conditions. In developing countries, exposure to HAV is virtually universal before the age of 10 years.2 With improving socioeconomic conditions, these countries enter a transition phase in which the virus is still prevalent in the population, but improving hygienic conditions delay the average age of infection.35 It is important to detect such shifts because disease severity increases with older age, and adults are thus more likely to experience morbidity when infected, leading to greater disease burden and significant health problems.

Safe and effective hepatitis A vaccines have been available for more than a decade and have proven to reduce disease burden and offer protection to at-risk populations.68 However, the epidemiologic shift in hepatitis A infection observed in intermediate endemic regions has driven the development of universal preventive strategies to be added to the targeting of at-risk groups.9 Very few epidemiologic studies to observe the pattern of HAV prevalence have been conducted in Lebanon. The current study was designed to detect changing patterns in age-related HAV seroprevalence in Lebanon. The effects of socioeconomic factors such as family type, ownership of the house, education level, and income were also explored in this study.

MATERIALS AND METHODS

This was a cross-sectional study conducted at four centers in Lebanon: Hotel Dieu De France Hospital, Beirut; Nini Hospital, Tripoli (North Lebanon); Hammoud Hospital, Saida (South Lebanon); and St. Georges Hospital, Beirut. Administratively, Lebanon is divided into five governorates, Al Biqa, Al Janub (South), Ash Shamal (North), Beirut, and Jabal Lubnan (Lebanon Mountain). Beirut and Jabel Lubnan are usually considered as forming greater Beirut. Data was collected from all governorates except Al Biqa (which represents about 20% of the total population of Lebanon). Hotel Dieu de France and St. George’s Hospitals serve Greater Beirut, Nini Hospital serves North Lebanon, and South Lebanon is served by Hammoud Hospital. The study protocol and the statement of informed consent were approved by the ethics committee of each center, and written informed consent was obtained from all subjects prior to study start. The study was conducted between 1 September 1999 and 31 July 2000, in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines in force at the time.

Enrollment and data collection.

Healthy volunteers aged 1 to 30 years of both sexes and varying socioeconomic and education status were invited to participate in this study. Subjects were recruited randomly from hospital staff and parents of patients and children coming for regular check-up at the above-mentioned study hospitals. After the signed informed consent was obtained from the participants or from their parents or guardians (in cases of minors), subjects were medically examined and checked for predefined inclusion/exclusion criteria. Subjects were excluded from participating in the study if they had jaundice at the time of entry into the study or if they had previously received vaccination against hepatitis A. Subjects with gastric, hepatic, or skin diseases were excluded from the study. No more than one individual per household was enrolled. A questionnaire was used to collect data from the subjects or parents/guardians of the subjects on age, gender, and various socioeconomic factors such as family type, ownership of the house, education level, and monthly income.

DEFINITIONS

Family type.

Study subjects were categorized into three groups: 1) parents and children living with subject, 2) parents, children, and relatives living with subject, and 3) subject is single and living alone.

Education level.

Education level of the parents/guardians was taken into consideration for subjects in the age group of 1–20 years, and the education level of the subject was taken into consideration for subjects in the age group of ≥ 21 years. Subjects/parents/guardians were classified as illiterate if they had no formal schooling or literate if they had. The literate subjects/parents/guardians were further classified by their schooling level into 1) subject/ parent/guardian has attended primary school, 2) subject/parent/guardian has attended secondary school, and 3) subject/parent/guardian has been in university.

Monthly income.

Subjects were stratified into one of the three income levels on an ad hoc basis using the minimum monthly salary [300,000 Lebanese pound (L£)] according to Lebanese laws10: low-income group was < 500,000 L£ for singles and < 700,000 L£ for families, medium-income group was 500,000 L£ to 1,500,000 L£ for singles and 700,000 L£ to 2,000,000 L£ for families, and high-income group was > 1,500,000 L£ for singles and > 2,000,000 L£ for families. During the study period, 1 US$ was about 1,500 L£.

Specimen collection and handling.

Blood samples were taken from healthy subjects (3 mL from children < 12 years and 5 mL from subjects ≥ 12 years) and stored at –20°C until tested at Hotel Dieu De France Hospital.

Serology.

Serum samples were analyzed for anti-HAV IgG antibodies using a commercial Microparticle Enzyme Immuno Assay kit (MEIA, Abbott Park, IL) from Abbott Laboratories. The assay cutoff for seropositivity was a reactivity ratio [(i.e. sample rate/cutoff rate (S/CO)] where cutoff rate is 50% of index calibrator value between 0 and 1.00. A subject was determined to be seropositive for anti-HAV antibodies when the reactivity of the assay was 0 < S/CO < 1.00.

Data handling and statistics.

Statistical analyses were performed using SAS ver. 6.12 (SAS, Cary, NC). The population included in these analyses was subjects whose demographic and serological data were available and who complied with the protocol-defined procedures. The percentage of subjects who were seropositive for hepatitis A was tabulated along with 95% confidence interval (95% CI). Anti-HAV seroprevalence was studied in subjects for the effect of age, gender, and various socioeconomic factors including family type, ownership of the house, education level, and monthly income. A multiple logistic regression analysis that included all factors found significantly influencing anti-HAV prevalence in univariate model was performed. The final model included age, gender, education, and family income level. The effects of all two-way interactions were checked among these significant factors. Significance level of 0.05 was used for all statistical tests in the analysis.

RESULTS

Study population.

Of 608 subjects enrolled, two were excluded from analysis as they were outside the protocol-defined age range of 1–30 years. Thus, HAV seroprevalence was studied in 606 subjects. About 45% of the study subjects were males. There were 43 (7.1%) subjects from center 1 (Hotel Dieu De France Hospital), 176 (29.0%) subjects from center 2 (Nini Hospital), 185 (30.5%) subjects from center 3 (Hammoud Hospital), and 202 (33.3%) subjects from center 4 (St. Georges Hospital) (Table 1).

HAV seroprevalence.

Of the 606 serum samples tested, 262 (43.2%) were seropositive for anti-HAV antibodies (95% CI: 39.2, 47.3%). Except for study center 1, where the number of subjects was too small to compare with the others, anti-HAV seropositivity rate was not different among study centers.

Multiple logistic regression analysis was performed on 599 subjects, who had no missing values with respect to factors included in the analysis (Table 2). Age, followed by education level, income, and gender (with gender being significant only in the univariate model) were the significant factors that were found to be influencing HAV seroprevalence. However, all two-way interactions among these significant factors were checked and none of them was significant. The other factors such as family type and ownership of the house did not show any such trend on influencing HAV seroprevalence.

Age.

Anti-HAV seroprevalence was studied in 1–5, 6–10, 11–15, 16–20, and ≥ 21 years age groups. Figure 1 shows that anti-HAV seropositivity rate increased considerably from lower age group to older age group (Univariate χ2 test for the trend P < 0.001). Approximately 78% of subjects in the age group of ≥ 21 years were seropositive for anti-HAV antibodies compared with children aged 1–10 years (11% in 1–5 years and 28% in 6–10 years). The probability of being anti-HAV seropositive was significantly higher for subjects ≥ 21 years when compared with that for subjects aged 1–5 years [odds ratio 65.1 (28.8, 146.9), adjusted for other factors] (Table 2).

Gender.

Overall, significantly fewer male subjects were seropositive for anti-HAV antibodies than females; 37% versus 49%, (P < 0.01; univariate χ2 test). However, gender, after controlling for confounding factors, was not significant and as such it can be concluded that there was no significant difference in probability of being anti-HAV seropositive between females and males.

Education level.

Education level was a significant factor influencing a subject’s anti-HAV seropositivity status. Based on multiple logistic regression analysis, seroprevalence rate was significantly higher in illiterates (AOR = 16) and subjects/parents/guardians who had attended primary school (AOR= 4) compared with subjects/parents/guardians who had received university education.

Monthly income.

On univariate analysis, HAV seroprevalence was found to be significantly different with HAV seroprevalence rate in low-income group being significantly higher (55%) than that observed in medium- (36%) and high-income groups (42%) (P < 0.01; univariate χ2 test). Based on multiple logistic regression analysis, the odds of being anti-HAV seropositive for subjects in low-income group was moderately higher [AOR = 1.6 (0.9, 2.9)] than that in high-income group. However, the odds of being anti-HAV seropositive was similar for subjects in medium-income group compared with those in high-income group [AOR = 0.7 (0.4, 1.2)].

DISCUSSION

The HAV prevalence pattern as observed in this multi-center study was of intermediate endemicity and was representative of the population in governorates that constitute about 80% of the Lebanese population. The seroprevalence of hepatitis A in Lebanon was last documented in 1982,11 although data on children aged 6 months to 15 years was updated in a study conducted in North Lebanon during 1996–1998.12 HAV seroprevalence rate in 1982 was 97.7% and 40% in Lebanese adults and children aged 1–5 years, respectively, as compared with 78.1% and 10.5%, respectively, in the current study. HAV seroprevalence rate was 85% in children aged 6–12 years in 1982 as compared with 30.8% to 37.6% in children aged 7–12 years in 1996–1998 and 27.7% in children aged 6–10 years in the current study. Although different populations were studied and sampling and assay methodology varied between the current study and the previous studies, this decrease in anti-HAV seroprevalence over the years indicates a shift in HAV seroprevalence from the younger to the older age groups.

The percentage of uninfected children was even higher for those belonging to medium- and high-income groups. A higher prevalence of anti-HAV antibodies was also detected in populations with lower education levels. Furthermore, no relation was found between anti-HAV seropositivity rate and gender, confirming data from an earlier study in Lebanon.12

This trend toward a shift in HAV seroepidemiological pattern from high to intermediate or even low endemicity has been a well-known epidemiologic feature in developing countries that underwent socioeconomic and hygienic improvements,1316 particularly in regions such as Latin America, Middle East, and Southeast Asia. Due to this gradual shift from high to intermediate endemicity for hepatitis A, there is a drop in HAV circulation and consequently the immunity to HAV infection falls rapidly, resulting in a growing pool of susceptible people. The probability of HAV epidemics increases due to the significant number of individuals susceptible to infection. The transition from high to low endemicity in HAV prevalence in developing countries has previously led to explosive outbreaks due to viral cross-contamination from endemic to nonimmune sectors of the population via food or water.17 The use of effective hepatitis A vaccination as a public health tool has become more and more essential as increasing numbers of individuals reach adolescence and adulthood without natural immunity to the disease and are therefore at risk of hepatitis A morbidity and mortality.1,18 Vaccines against hepatitis A have been developed and have been shown to provide long-term protection against the disease.6,19 The WHO position paper on hepatitis A vaccines1 states that in countries of intermediate endemicity, large-scale childhood vaccination should be considered as a supplement to health education and improved sanitation. Such immunization programs against hepatitis A have already been implemented in several countries including Spain,20 Italy,21 and Israel.22 The effectiveness and cost-benefit analysis of hepatitis A vaccination programs proved to be both medically and economically justifiable in these countries.2325

Currently, Lebanon does not have a national immunization policy against hepatitis A. The shift in epidemiologic pattern observed in Lebanon and the availability of safe and effective hepatitis A vaccines stress the need to consider appropriate vaccination strategies to reduce the risk of hepatitis A morbidity and mortality in susceptible children and adolescents. A follow-up study to evaluate the impact and feasibility of population-based hepatitis A vaccination programs is recommended, with due consideration to the implementation of hepatitis A vaccination program in the national immunization schedule of Lebanon.

Table 1

HAV prevalence rate by study center

CenterNumber of subjectsPercent seropositive (%)95% CI
95% CI, 95% confidence interval, lower and upper limits.
Greater Beirut
    Hotel Dieu de France Hospital4314.05.327.9
    St. George’s Hospital20241.634.748.7
North Lebanon
    Nini Hospital17649.441.857.1
South Lebanon
    Hammoud Hospital18545.938.653.4
Total60643.239.247.3
Table 2

Crude and adjusted odds ratios for the association between selected sociodemographic factors and anti-HAV seropositivity

VariablesNo. of subjects (N = 599)*Percent seropositive (%) (N = 599)Crude OR (95% CI)Adjusted OR† (95% CI)
OR, odds ratio; CI, confidence interval.
* Seven subjects had incomplete data on factors included in the analysis.
† Adjusted for all other variables in the model.
Age
    1–5 years17210.511
    6–10 years11227.73.3 (1.7–6.2)3.3 (1.7–6.3)
    11–15 years12257.411.5 (6.3–21.1)12.7 (6.7–24.1)
    16–20 years9770.120.1 (10.4–38.6)22.4 (11.1–45.1)
    ≥ 21 years9678.130.6 (15.4–60.7)65.1 (28.8–146.9)
Gender
    Male27137.311
    Female32849.11.6 (1.2–2.3)1.1 (0.7–1.7)
Education level
    University19441.211
    Secondary20041.51.0 (0.7–1.5)2.3 (1.3–4.2)
    Primary19847.01.3 (0.8–1.9)3.6 (1.9–7.0)
    Illiterate785.78.5 (1.0–72.3)15.9 (1.5–173.6)
Income
    High17541.711
    Medium22836.00.8 (0.5–1.2)0.7 (0.4–1.2)
    Low19654.61.7 (1.1–2.5)1.6 (0.9–2.9)
Figure 1.
Figure 1.

Overall HAV seroprevalence rate by age group (χ2 test for the trend P < 0.001).

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 73, 2; 10.4269/ajtmh.2005.73.453

*

Address correspondence to Remon Abu-Elyazeed, GlaxoSmithKline Biologicals, 150 Beach Road, #22-00 Gateway West, Singapore 189720. E-mail: remon.abu-elyazeed@gsk.com

Authors’ addresses: Robert G. Sacy, St. Georges Hospital, Achrafieh, Lebanon, Telephone: + 961 1 585700, Fax: + 961 1 582560, E-mail: rsacy@lb.refer.org. Mirna Haddad, Hotel-Dieu Hospital, Achrafieh, Lebanon, Telephone: + 961 1 615300 ext. 8725/8735/8730, Fax: + 961 6 448442, E-mail: germanos@inco.com.lb. Ghassan Baasiri, Hammoud Hospital, Saida, Lebanon, Telephone: + 961 7 723111, Fax: + 961 7 725833. Adlette Khoriati, Nini Hospital, Maarad Street, Tripoli, Lebanon, Telephone: + 961 6 628434, Fax: + 961 6 448442, E-mail: khorina@dm.net.lb. Bernard J. Gerbaka, Hotel-Dieu Hospital, Achrafieh, Lebanon, Telephone: + 961 1 615400, Fax: + 961 1 611636, + 961 9 933277, E-mail: pedhdf@usj.edu.lb. Remon Abu-Elyazeed, GlaxoSmithKline Biologicals, 150 Beach Road, #22-00 Gateway West, Singapore 189720, E-mail: remon.abu-elyazeed@gsk.com.

Acknowledgments: The study was supported by GlaxoSmithKline Biologicals. The authors thank Dr. Hussein Makki and Drs. Carlo Akatcherian and Raymond Michael for their significant contributions in recruiting subjects at Hammoud Hospital, Saida, and Hotel Dieu de France Hospital, Beirut, respectively; and Mr. Vincent Mazraanin for his assistance in conducting all the necessary laboratory procedures at Nini Hospital, Tripoli, North Lebanon.

REFERENCES

  • 1

    WHO, 2000. Hepatitis A vaccines, WHO position paper. Wkly Epidemiol Rec 75 :38–44.

  • 2

    Battegay M, Gust ID, Feinstone SM, 1995. Hepatitis A virus. Mandell JL, Benett JE, eds. Principles and Practice of Infectious Disease. New York: Churchill Livingstone 1636–1656.

  • 3

    Hadler SC, 1991. Global impact of hepatitis A virus infection changing patterns. Hollinger FB, Lemon SM, Margolis H, eds. Viral Hepatitis and Liver Disease. Baltimore: Williams & Wilkins, 14–20

  • 4

    Gust ID, 1992. Epidemiological patterns of hepatitis A in different parts of the world. Vaccine 10 :S56–S58.

  • 5

    Gay NJ, Morgan-Capner P, Wright J, Farrington CP, Miller E, 1994. Age-specific antibody prevalence to hepatitis A in England: implications for disease control. Epidemiol Infect 113 :113–120.

    • Search Google Scholar
    • Export Citation
  • 6

    Werzbeger A, Mensch B, Kuter B, Brown L, Lewis J, Sitrin R, Miller W, Shouval D, Wiens B, Calandra G, 1992. A controlled trial of formalin-inactivated hepatitis A vaccine in healthy children. N Engl J Med 327 :453–457.

    • Search Google Scholar
    • Export Citation
  • 7

    Innis BL, Snitbhan R, Kunasol P, Laorakpongse T, Poopatanakool W, Kozik CA, Suntayakorn S, Suknuntapong T, Safary A, Tang DB, Boslego JW, 1994. Protection against hepatitis A by an inactivated vaccine. JAMA 271 :1328–1334.

    • Search Google Scholar
    • Export Citation
  • 8

    Andre FE, D’Hondt E, Delem A, Safary A, 1992. Clinical assessment of the safety and efficacy of an inactivated hepatitis A vaccine: rationale and summary of findings. Vaccine 10 (Suppl 1):S160–S168.

    • Search Google Scholar
    • Export Citation
  • 9

    Andre F, Van Damme P, Safary A, Banatvala J, 2000. Inactivated hepatitis A vaccine: immunogenicity, efficacy, safety and review of official recommendations for use. Expert Rev Vaccines 1 :9–23.

    • Search Google Scholar
    • Export Citation
  • 10

    Lebanese decree no 8733. Fixing the minimum wages of the employees and workers as well as the increase of the cost of living. Lebanese Official Gazette (in Arabic: Jaride Al Rasmiye) Lebanon, Published on 8 July 1996.

  • 11

    Shammaa MH, Abu-Samra S, Salameh V, Nassar NT, 1982. The significance of anti-HAV in different population sectors in Lebanon: a comparative seroepidemiologic study. Int J Epidemiol 11 :406–409.

    • Search Google Scholar
    • Export Citation
  • 12

    Kalaajieh W, Rima A, Dennaoui M, Al Khodayry R, 2000. Seroprevalence of hepatitis A antibodies in Lebanese children. Med Mal Infect 30 :757–761.

    • Search Google Scholar
    • Export Citation
  • 13

    Tanaka J, 2000. Hepatitis A shifting epidemiology in Latin America. Vaccine 18 (Suppl 1):S57–S60.

  • 14

    Poovorawan Y, Theamboonlers A, Sinlaparatsamee S, Chaiear K, Siraprapasiri T, Khwanjaipanich S, Owatanapanich S, Hirsch P, 2000. Increasing susceptibility to HAV among members of the young generation in Thailand. Asian Pac J Allergy Immunol 18 :249–253.

    • Search Google Scholar
    • Export Citation
  • 15

    Tufenkeji H, 2000. Hepatitis A shifting epidemiology in the Middle East and Africa. Vaccine 18 (Suppl 1):S65–S67.

  • 16

    Green MS, Aharonowitz G, Shohat T, Levine R, Anis E, Slater PE, 2001. The changing epidemiology of viral hepatitis A in Israel. Isr Med Assoc J 3 :347–351.

    • Search Google Scholar
    • Export Citation
  • 17

    Halliday ML, Kang LY, Zhou TK, Hu MD, Pan QC, Fu TY, Huang YS, Hu SL, 1991. An epidemic of hepatitis A attributable to the ingestion of raw clams in Shanghai, China. J Infect Dis 164 :852–859.

    • Search Google Scholar
    • Export Citation
  • 18

    WHO, 1995. Public health control of hepatitis A: memorandum from a WHO meeting. Bull WHO 73 :15–20.

  • 19

    McMahon BJ, Beller M, Williams J, Schloss M, Tanttila H, Bulkow L, 1996. A program to control an outbreak of hepatitis A in Alaska by using an inactivated hepatitis A vaccine. Arch Pediatr Adolesc Med 150 :733–739.

    • Search Google Scholar
    • Export Citation
  • 20

    Salleras L, Bruguera M, Buti M, Domingez A, 2000. Prospects for vaccination against hepatitis A and B in Catalonia (Spain). Vaccine 18 (Suppl 1):S80–S82.

    • Search Google Scholar
    • Export Citation
  • 21

    Germinario C, Lopalco PL, Chicanna M, Da Villa G, 2000. From hepatitis B to hepatitis A and B prevention: the Puglia (Italy) experience. Vaccine 18 (Suppl 1):S83–S85.

    • Search Google Scholar
    • Export Citation
  • 22

    Fishman RH, 1998. Hepatitis A vaccine for Israeli children. Lancet 352 :88846.

  • 23

    Dominguez A, Salleras L, Carmona G, Batalla J, 2003. Effectiveness of a mass hepatitis A vaccination program in pre-adolescents. Vaccine 21 :698–701.

    • Search Google Scholar
    • Export Citation
  • 24

    Demicheli V, Carniglia E, Fucci S, 2003. The use of hepatitis a vaccination in Italy: an economic evaluation. Vaccine 21 :2250–2257.

  • 25

    Ginsber GM, Slater PE, Shouval D, 2001. Cost-benefit analysis of a nationwide infant immunization programme against hepatitis A in an area of intermediate endemicity. J Hepatol 34 :92–99.

    • Search Google Scholar
    • Export Citation

Author Notes

Reprint requests: Dr. Remon Abu-Elyazeed, GlaxoSmithKline Biologicals, 150 Beach Road, #22-00 Gateway West, Singapore 189720, E-mail: remon.abu-elyazeed@gsk.com.
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