Cost-effectiveness of Universal Infant Hbv Vaccination

To evaluate the cost-effectiveness of four infant vaccination strategies aimed at protecting the Thai population against hepatitis B virus (HBV) infection, vaccination and giving hepatitis B immunoglobulin (HBIg) to high-risk infants were compared with universal vaccination of infants and no vaccination. An analytic decision model was used to estimate the clinical and economic consequences of HBV for a hypothetical cohort of newborns for each of the immunization strategies. The model focused on the numbers and the costs of cases prevented. The decision model examined four different HBV management strategies: 1. screening for HBsAg, and vaccination; 2. screening for HBsAg, then HBeAg, and vaccination; 3. universal vaccination of all neonates; and 4. no vaccination. The cost-effectiveness per case prevented for Strategy 1 was 292.79 baht; for Strategy 2, 264.34 baht; for Strategy 3, 151.05 baht; and for Strategy 4, 0 baht. The incremental cost comparing Strategy 3 to Strategy 4 was 6,521 baht; comparing Strategy 2 to Strategy 3, 20,000 baht; and comparing Strategy 1 to Strategy 2, 95,000 baht. There is no socially acceptable threshold value for cost per case prevented to guide decisions on funding health care interventions. Strategy 3 should certainly be continued. Nevertheless, based on these results, Strategy 2 may be considered, despite the incremental cost being about 2 times that of Strategy 3, as it might represent a worthwhile investment of public funds. mucous membrane penetration around the time of delivery (Goudeau et al, 1983). In countries highly endemic for HBV, such as in Southeast Asia, perinatal transmission of HBV from infected mothers to their infants often leads to severe long-term sequelae. The rate of hepatitis B transmission from mother to child is increased if the mother has had acute hepatitis B infection in the last trimester of pregnancy, or if she is carrying the hepatitis B ‘e’ antigen (HBeAg) in addition to HBsAg. The transmission rates are 85%, if HBeAg positive, and 15-20%, if HBeAg negative; 85-95% of infected infants become chronic carriers (Beasley et al, 1977, 1983; Stevens et al, 1979, 1985). Most neonatal infections are asymptomatic or mild. The risk for these carrier children to die in adulthood of primary hepatocellular carcinoma (HCC) or cirrhosis is approximately 25% (Shiraki et al, 1977; Beasley et al, 1982, 1984). Their deaths always coincide with maximum familial and financial responsibilities, and these children become carSOUTHEAST ASIAN J TROP MED PUBLIC HEALTH 694 Vol 36 No. 3 May 2005 rier mothers themselves, perpetuating the cycle of perinatal transmission (Kane et al, 1988). Prevention of perinatal transmission is possible if immunoprophylaxis is administered to babies-at-risk, shortly after birth (Beasley et al, 1981, 1983; Tada et al, 1982; Wong et al, 1984; Stevens et al, 1985). The vaccine, as well as the simultaneous administration of the vaccine and HBIg, have proven to be highly immunogenic and effective in preventing vertical transmission (Poovorawan et al, 1989, 1992). Prenatal HBsAg screening would identify infected mothers, thus allowing for immunization of their newborns with hepatitis B immunoglobulin (HBIg) and hepatitis B vaccine – a regimen that is 85-97% effective in preventing the development of a chronic HBV carrier state (Beasley et al, 1983; Wong et al, 1984; Stevens et al, 1985, 1987; Poovorawan et al, 1989, 1992). Use of vaccine alone can prevent the chronic carrier state in 70-95% of such infants (Wong et al, 1984; Xu et al, 1985; Poovorawan et al, 1990). The Global Advisory Group of the Expanded Program on Immunization has recommended, with World Health Assembly endorsement, that countries with a prevalence of HBV carriers exceeding 2% should add hepatitis B vaccine to their routine infant immunization schedules (World Health Assembly, 1992). Universal immunization remains the only strategy capable of efficiently reducing the numbers of acute hepatitis patients and chronic carriers; hence, decreasing the long-term disease burden, such as with HCC. In addition, universal hepatitis B vaccination, as an integral part of the national Expanded Program on Immunization (EPI), has been found to provide long-term protective immunity (Poovorawan et al, 2002). In countries with high prevalence and evidence of HBV vertical transmission, such as China, Southeast Asia, and the Far East, the first dose of hepatitis B vaccine needs to be administered as soon as possible after birth, preferably within 24 hours. The Thai Ministry of Public Health (MoPH) has included the control of HBV infection as part of the EPI since 1992. HB vaccine is given, along with the other EPI vaccines, at birth and at the age of 2 and 6 months. Universal immunization of all neonates in Thailand has markedly reduced the carrier rate to 0.7% (Poovorawan et al, 2000). However, cost-effectiveness studies of maternal HBsAg screening and the vaccination of babies at risk have never been undertaken in the context of health care service in Thailand. Routine HBsAg screening of all pregnant women may be initiated as part of regular antenatal checkups, where the facilities are available. However, selective passive-active immunization also requires a supply of HBIg. This study was carried out to estimate an economic rationale for introducing routine prenatal HBsAg screening and prescribing combined passive-active immunization to babies-at-risk. MATERIALS AND METHODS Models and strategies We developed an analytic decision model, to estimate the clinical and economic consequences of HBV, for a hypothetical cohort of newborns with respect to each of the immunization strategies from the health care provider’s perspective. The model focused on the number and the cost of cases prevented. The decision model examined four different HBV management strategies as follows (see details in Fig 1). Strategy 1. Screening for HBsAg, then vaccination: a mixed-population strategy of screening all pregnant women, before or during labor, for evidence of active HBV infection (HBsAg positive); then administering HBV vaccine and hepatitis B immunoglobulin (HBIg) to those HBsAg positive, but administering only HBV vaccine to those negative for HBsAg. Strategy 2. Screening for HBsAg then HBeAg if HBsAg positive, and vaccination: a mixed-population strategy of screening all pregnant women, for evidence of active HBV infection (HBsAg positive) then for evidence of HBeAg (HBeAg positive) if HBsAg positive; and administering HBV vaccine and hepatitis B immunoglobulin (HBIg) to those positive for HBeAg, but administering only HBV vaccine to those negative for HBsAg, or those HBsAg positive but HBeAg negative. Strategy 3. Universal vaccination: vaccination of all neonates. COST-EFFECTIVENESS OF UNIVERSAL INFANT HBV VACCINATION Vol 36 No. 3 May 2005 695 Strategy 4. No vaccination. Since universal vaccination has now been implemented in Thailand and the risk of HBV infection is high, the ‘no vaccination’ strategy was considered in the decision tree for comparison purposes. The target population was a representative cohort of the 800,000 neonates that are born annually in Thailand. The decision model used in this analysis was developed after a critical review of the literature, with input from HBV experts to ensure accuracy and validity. Cost Data for 2004 on actual average payments of patients for outpatient hospital care, diagnostic tests, and HBIg were obtained from King Chulalongkorn Hospital (a publicly funded university hospital in Bangkok). Costs of HBV vaccines were obtained from the Disease Control Department, Ministry of Public Health, where the vaccine was bought and supplied to the hospitals in the EPI. The details of the cost are shown in Table 1. The model was based on the perspective of the health care provider and was confined to direct medical costs. Direct non-medical costs, such as travel costs incurred in the course of receiving medical care, and indirect costs were excluded from the analyses. Incremental outcome effectiveness and costeffectiveness Incremental cost-effectiveness was calculated to compare each alternative management strategy (Strategies 1-3) to Strategy 4 (no vaccination) and was expressed as the difference in cost (Thai baht) incurred per additional case prevented.