Third Dose Of Hepatitis Research Articles

Antibody Response against Vaccine Antigens in Children after TCRαβ-Depleted Haploidentical Stem Cell Transplantation: Is It Similar to That in Recipients with Fully Matched Donors?

Recipients of hematopoietic stem cell transplantation (HSCT) with HLA-mismatched donors are more immune suppressed than those with fully matched donors. The immunologic response to vaccines also may differ in HLA-mismatched haploidentical HSCT recipients. In this study, we aimed to evaluate the antibody response to vaccines in pediatric TCRαβ-depleted haploidentical HSCT recipients. This longitudinal study included a study group of 21 children who underwent haploidentical HSCT without CD19 depletion and with TCRαβ depletion and a control group of 38 children who underwent fully matched donor HSCT. Antibody levels were quantified by serologic tests before vaccination and after each dose against tetanus, diphtheria, pneumococcus, hepatitis B, hepatitis A, measles, rubella, mumps, and varicella. The median recipient age was significantly lower (P=.037) and the median donor age was significantly higher (P=.000) in the haploidentical group compared with the fully matched group. At the months 1, 3, 6, 9 and 12 post-transplantation, the median CD4, CD8, and CD19 cell counts and lymphocyte counts were similar in the haploidentical and fully matched groups. The median natural killer cell count was higher in the haploidentical group at the months 1, 3, and 6 post-transplantation (P=.001, .006, and .004, respectively). The median time to first vaccination was similar in the 2 groups (12.5 [range, 11 to 14] months for the haploidentical group and 11 [range, 9 to 13] months for the fully matched group; P=.441). Seroprotection rates were 100% in both groups after the second and third doses of diphtheria vaccine, the third dose of tetanus vaccine, the third dose of hepatitis B vaccine, the second and third doses of pneumococcal conjugate vaccines (PCV13), and pneumococcal polysaccharide vaccine (PSPV23), although lower after the initial doses and before vaccination. Seroprotection for hepatitis A, rubella, and varicella was >90% in the fully matched group and 100% for the haploidentical group after the second doses. Measles and mumps seroprotection rates were >80% in the haploidentical group and approximately 70% for the fully matched group after the second dose. Antibody response and seroprotection rates against vaccine antigens were similar in the haploidentical group and the fully matched when revaccination was started at 12 months post-transplantation. These findings support the idea that TCRαβ-depleted haploidentical HSCT recipients can be revaccinated according to the same vaccination schedule as fully matched HSCT recipients. Revaccination earlier after transplantation and vaccine responses for recipients of different types of HSCT should be evaluated in future studies.

Immunogenicity of aluminum-adsorbed hepatitis A vaccine (Havrix®) administered as a third dose after primary doses of Japanese aluminum-free hepatitis A vaccine (Aimmugen®) for Japanese travelers to endemic countries.

Hepatitis A vaccination is recommended for travelers to endemic countries. Several inactivated aluminum-adsorbed hepatitis A vaccines are available worldwide, but only one licensed hepatitis A vaccine is available in Japan. This vaccine is a lyophilized inactivated aluminum-free hepatitis A vaccine (Aimmugen®). The standard schedule of Aimmugen® is three doses (at 0, 2-4 weeks, and 6 months). Japanese people will go abroad after receiving 2 doses of Aimmugen®. Some long-term travelers will receive the third dose of hepatitis A vaccine at their destination, at 6-24 months after 2 doses of Aimmugen®. Aimmugen® is not available in countries other than Japan. They receive inactivated aluminum-adsorbed hepatitis A vaccine instead of a third dose of Aimmugen®. This study was undertaken to determine whether the booster vaccination with an aluminum-adsorbed hepatitis A vaccine is effective following two doses of Aimmugen®. Subjects were healthy Japanese adults aged 20 years or older who had received two doses of Aimmugen®. Subjects received a booster dose of Havrix®1440 intramuscularly as the third dose. Serology samples for hepatitis A virus antibody titers were taken 4-6 weeks later. Anti-hepatitis A virus antibody titers were measured by an inhibition enzyme-linked immunosorbent assay. Subjects were 20 healthy Japanese adults, 6 men and 14 women. The mean age ± standard deviation was 37.2 ± 13.3. The seroprotection rate (SPR, anti-hepatitis A virus antibody titer ≥10 mIU/mL) was 85% at enrollment, and increased to 100% after vaccination with Havrix®. The geometric mean anti-hepatitis A virus antibody titer increased from 39.8 mIU/mL to 2938.2 mIU/mL. The three scheduled doses consisting of two doses of Aimmugen® plus a third dose with Havrix® is more immunogenic than using only two doses of Aimmugen®. The vaccination with Havrix® could be allowed to be used instead of a third dose of Aimmugen®. (UMIN000009351).

Epidemiology of viral hepatitis

Understanding the country-specific epidemiology of disease, which may vary greatly among countries, is crucial for identifying the most appropriate preventive and control measures. An overview of the local epidemiology of viral hepatitis in Croatia is given in this paper. The overall prevalence of hepatitis B in Croatia is low (less than 2% HBsAg carriers in the general population). Hepatitis B incidence and prevalence began to decline significantly following the introduction of universal hepatitis B vaccination in 1999. Information on HBsAg seroprevalence is derived from routine testing of certain subpopulations (pregnant women, blood donors) and seroprevalence studies mostly targeted at high-risk populations. Universal childhood vaccination against hepatitis B remains the main preventive measure. We recommend testing for immunity one to two months after the third dose of hepatitis B vaccine for health-care workers. The incidence and prevalence of hepatitis C have also been declining in the general population. The main preventive measures are ensuring safety of blood products, prevention of drug abuse, and harm reduction programs for intravenous drug users. Hepatitis A incidence has declined dramatically since fifty years ago, when thousands of cases were reported annually. In the last five years, an average of twenty cases have been reported per year. The reduction of hepatitis A is a consequence of improved personal and community hygiene and sanitation. Hepatitis D has not been reported in Croatia. The risk of hepatitis D will get to be even smaller as the proportion of population vaccinated against hepatitis B builds up. Hepatitis E is reported only sporadically in Croatia, mostly in persons occupationally in contact with pigs and in travelers to endemic countries. In conclusion, Croatia is a low prevalence country for hepatitides A, B and C. Hepatitis D has not been reported to occur in Croatia and there are only sporadic cases of hepatitis E. Since hepatitis A is a rare disease occurring sporadically, which is a consequence of improved sanitation and hygiene, hepatitides B and C are the main causes of viral hepatitis in Croatia. The introduction of universal mandatory hepatitis B vaccination of schoolchildren in 1999 resulted in a decrease in the incidence of hepatitis B, which is most pronounced in adolescents and young adults, and further decrease in the incidence and prevalence is expected as the pool of susceptible individuals decreases through vaccination. The incidence of hepatitis C is decreasing as well. In spite of a relatively favorable epidemiological situation, hepatitis B and C are still a significant public health burden with an estimated 25,000 persons chronically infected with HBV and about 40,000 persons chronically infected with HCV in Croatia.

Randomized Trial of the Immunogenicity and Safety of the Hepatitis B Vaccine Given in an Accelerated Schedule Coadministered with the Human Papillomavirus Type 16/18 AS04-Adjuvanted Cervical Cancer Vaccine

The human papillomavirus type 16/18 (HPV-16/18) AS04-adjuvanted cervical cancer vaccine is licensed for females aged 10 years and above and is therefore likely to be coadministered with other licensed vaccines, such as hepatitis B. In this randomized, open-label study, we compared the immunogenicity of the hepatitis B vaccine administered alone (HepB group) or with the HPV-16/18 AS04-adjuvanted vaccine (HepB+HPV group) in healthy women aged 20 to 25 years (clinical trial NCT00637195). The hepatitis B vaccine was given at 0, 1, 2, and 12 months (an accelerated schedule which may be required by women at high risk), and the HPV-16/18 vaccine was given at 0, 1, and 6 months. One month after the third dose of hepatitis B vaccine, in the according-to-protocol cohort (n = 72 HepB+HPV; n = 76 HepB), hepatitis B seroprotection rates (titer of ≥10 mIU/ml) were 96.4% (95% confidence interval [CI], 87.5 to 99.6) and 96.9% (CI, 89.2 to 99.6) in the HepB+HPV and HepB groups, respectively, in women initially seronegative for anti-hepatitis B surface antigen (HBs) and anti-hepatitis B core antigen (HBc). Corresponding geometric mean titers of anti-HBs antibodies were 60.2 mIU/ml (CI, 40.0 to 90.5) and 71.3 mIU/ml (CI, 53.9 to 94.3). Anti-HBs antibody titers rose substantially after the fourth dose of hepatitis B vaccine. All women initially seronegative for anti-HPV-16 and anti-HPV-18 antibodies seroconverted after the second HPV-16/18 vaccine dose and remained seropositive up to 1 month after the third dose. Both vaccines were generally well tolerated, with no difference in reactogenicity between groups. In conclusion, coadministration of the HPV-16/18 AS04-adjuvanted vaccine did not affect the immunogenicity or safety of the hepatitis B vaccine administered in an accelerated schedule in young women.

Immunity to hepatitis B vaccine among health care workers

The aim of this study was to determine the level of anti-HBsAg (hepatitis B surface antigen) in vaccinated high risk group. We measured anti-HBsAg concentration in blood sera of adult students aged from 19 to 37 years old. Five milliliters (5 ml) of blood sample was taken from 210 cases four months after the second dose and 126 out of 210 cases three months after the third dose of hepatitis B vaccination. All blood samples were analyzed for anti-HBsAg by ELISA method. 125 out of 210 samples (59.5%) showed anti-HBsAg concentrations higher than 20 mIu/ml and considered immune after the second dose of hepatitis B vaccination. Also, 99.2% of samples had anti-HBsAg higher than 20 mIu/ml three months after the third dose of the vaccination. Non-immune cases in males were more than females (41.2% vs.40.1%). In conclusions, our results reinforce the importance of hepatitis B vaccine in adolescents and suggest that three dose of hepatitis B vaccine is necessary to increase the seropositive rate of anti-HBsAg in adults.

Improved immunization practices reduce childhood hepatitis B infection in Tonga

Background Hepatitis B infection is hyper-endemic in Tonga and 19% of pregnant women test positive for hepatitis B surface antigen (HBsAg). Routine childhood immunization against hepatitis B was introduced in 1989 and the target for elimination was set at <1% HBsAg prevalence in children. A study conducted in 1998, a decade after the introduction of hepatitis B immunization, found the HBsAg prevalence to be 3.8% in pre-school children. The finding resulted in the strengthening of the delivery of hepatitis B vaccine with emphasis on providing the first dose within 24 h after birth. The aim of this study was to measure the impact of improved immunization practices on the prevalence of hepatitis B infection in pre-school children, and to assess the progress towards hepatitis B elimination in Tonga. Measured outcome Prevalence of HBsAg antigen. Type of study Cross-sectional study. Methods Children aged 6–59 months who were admitted to Vaiola Hospital, Nuku’alofa, Tonga, and had blood collected for clinical investigation, were tested for HBsAg with a rapid serological test (Abbott Determine ®). A total of 449 children were recruited and interviewed and 375 (84%) were tested for HBsAg. Convenience testing was chosen, as it was likely to be a relatively unbiased method in this situation where all children on the island have good and equitable access to hospital services. Immunization status was checked against the children's immunization cards and cross-checked against the records kept by the public health nurses. Information about socio-economic status, parent education, blood transfusion, breast-feeding, mode of delivery, and place of birth was collected through interviews with mothers using a standardized questionnaire. Results Three children tested positive for HBsAg resulting in a prevalence of 0.8% (CI 0.2–2.5%). Hepatitis B 1 (Hep B 1) immunization coverage was found to be high, 99.1% (CI97.7–99.7) and 91.9% (CI 88.9–94.2) of children received the first dose of hepatitis B vaccine within 24 h after birth. Coverage for the third dose of hepatitis B vaccine was 97.6% (CI 95.5–98.7) and of the children with complete immunization 84.7% (CI 80.9–87.9) had received all three doses by 6 months of age. Conclusions The results show that the instituted changes in the delivery of hepatitis B vaccine have been effective in reducing the transmission of hepatitis B to children and indicate that Tonga appears to have achieved the elimination target of less than 1% HBsAg prevalence in children. This convenience survey used a simple, cost effective and reproducible study design. Convenience testing can be recommended for surveillance of the effectiveness of immunization programmes in settings where the population has good access to health services.

Couverture vaccinale des enfants de CM2 (10-11 ans) du Finistère, France, en 2004

Within the context of a cross-sectional survey to study the health status of 10 & 11-year-olds in Finistere (western France) in 2004, their vaccination status was also investigated. A random sample of 1003 children was selected, and 992 completed questionnaires were returned in response to the status of tuberculosis vaccination. 67% of children's cases corresponded to the acceptable vaccination status according to the French 1990 guidelines, including the BCG test. Prime injections were correctly carried out (ranging from 95% for measles to 97.7% for trivalent diphtheria, tetanus, and poliomyelitis [DTP] vaccines). Vaccine coverage rates were seen to decrease with the follow-up doses of injections required: 89% for the fourth dose of pertusis (whooping cough) vaccine and 91.9% for the fifth does of DTP. Coverage was remarkably lower for the third dose of hepatitis B vaccine and the second dose of trivalent measles, mumps, and rubella which have both been recommended later in France. The community and living environment (urban & rural) is a common factor found closely associated with vaccination compliance and coverage rates. For the most part, the vaccination rates for these children in Finistère were higher than the national ones.

Vaccination Coverage in 14-Year-Old Adolescents: Documentation, Timeliness, and Sociodemographic Determinants

The objective of this study was to measure the coverage and influencing determinants of hepatitis B virus, measles-mumps-rubella, and Meningococcus serogroup C vaccination in 14-year-old adolescents in Flanders, Belgium, in 2005. A total of 1500 adolescents who were born in 1991 and were living in Flanders were selected with a 2-stage cluster sampling technique. Home visits to copy vaccination documents and complete a questionnaire on sociodemographic and other related factors were conducted by trained interviewers. Only documented vaccination dates were accepted. Missing data were, when possible, retrieved through medical charts of the School Health System. For 1344 (89.6%) adolescents, a home visit was performed. Vaccination coverage was 75.7% for the third dose of hepatitis B virus, 80.6% for the first dose and 83.6% for the second dose of measles-mumps-rubella, and 79.8% for Meningococcus serogroup C. Only 74.6% of the adolescents had proof of 2 measles-mumps-rubella vaccines. Although 1006 (74.8%) adolescents had vaccination data available at home at the time of the interview, only 427 (31.8%) were able to show written proof of all studied vaccines. The probably underestimated coverage rates are well below World Health Organization recommendations, but timeliness of vaccinations was respected. Univariate logistic regression showed that unemployment of the father as proxy measure of socioeconomic status was detrimental for vaccination status, in contrast to partial employment of the mother, which was a favorable factor. Previously unreported determinants of lower coverage rates inferred from this study are single divorced parents, larger families (> or = 4 children), lower adolescent educational level, enrollment in special education, and repeating a grade. Insufficient documentation is a major barrier in this vaccination coverage study. More attention should go to those with the lowest coverage rates, such as adolescents from large families, with separated parents, and with a lower socioeconomic background.

Hepatitis B vaccination among medical students

Sir, The incidence of liver disease associated with the hepatitis B virus (HBV) is a world-wide public health problem. The disease is transmitted by perinatal, parenteral, sexual routes.(1) Healthcare workers, particularly surgeons, pathologists, dentists and physicians working in hemodialysis and oncology units, are at a higher risk of contracting HBV infection via minor skin cuts and accidental needle punctures.(2) Since proper vaccination can prevent HBV infection, complete hepatitis B vaccination is necessary for medical and paramedical students. The present study was carried out to observe the attitude and practice of medical students towards hepatitis B vaccination and find out if they completed all three doses and, if not, elicit the reasons for incomplete vaccination. The study group consisted of medical students admitted in the year 2000 and 2001. After giving a brief introduction on the study, pre-tested, self-administered, anonymous questionnaires were distributed with reference to hepatitis B immunization history and reasons for non-compliance among those who had not completed three doses. The questionnaires were distributed in a single day in June 2005 in order to avoid sharing of information. The data were analysed statistically using Chi-square test. Out of the 250 questionnaires circulated, 217 (M = 130, F = 87) were returned, and the response rate was 86.8%. Among them, only 29 (22.3%) boys and 21 (24.1%) girls maintained their vaccination record. Nineteen (8.7%) (9 boys, 10 girls) students had already completed three doses and received booster dose on admission. Unfortunately, without vaccination against HBV, 12 (9.2%) boys and 3 (3.4%) girls produced certificates from qualified and registered medical practitioners. Among the rest (183), the numbers that received the first, second and third dose of hepatitis B vaccination were 109 (100%), 62 (56.9%) and 33 (30.3%) boys, respectively, and 74 (100%), 41 (55.4%) and 31 (41.9%) girls, respectively. Complete coverage was significantly (P < 0.05) more among girls. The reasons for non-compliance were many and are mentioned in Table 1. Some dominant reasons were forgetfulness (38.8%), no reminder (35.8%), lack of knowledge on hepatitis B infection (23.1%), lack of compulsion (20.1%), etc. Table 1 Reasons for non-compliance of hepatitis B vaccination Medical students are susceptible to HBV infection during their exposure to clinical cases and different procedures. Hence, medical students were advised to have vaccination against HBV before coming to clinical side, as they acquire good immune response with immune memory.(3) Three doses of vaccination are provided free of charge to all the students (both day scholars and hostelites) during the time of admission. They were provided with a vaccination card indicating the schedule for subsequent doses. For want of follow-up, reminding, monitoring and supervising systems, 119 did not complete vaccination. Hence, it is suggested that the students and their parents/family members who come on the day of admission should be educated on HBV infection and motivated for successful and effective vaccination. The process of vaccination may be completed with the help of student council. The study also highlights the need for a national policy in countries where hepatitis B vaccination to health care personnel is not made mandatory. Limitations of this study include non-availability of vaccination record in many and recall bias in addition to non-screening of their blood for hepatitis B surface antigen and antibodies too.

Status epilepticus and lymphocytic pneumonitis following hepatitis B vaccination

The case reported refers to a patient who developed status epilepticus in the day of her third dose of hepatitis B vaccination and we review the literature on this subject. A 12 year-old girl, without a relevant previous history, taking no drugs, developed a seizure attack followed by unconsciousness, and eventually died after three days of her third dose of hepatitis B (HB) vaccination. Autopsy study revealed cerebral edema with congestion and herniation and diffuse interstitial type pneumonitis. There seem to be a straight forward time relationship between the third HB vaccine, the event of convulsion and the sudden death of the patient. We suggest that, in some cases, vaccination may be the triggering factor for autoimmune and neurological disturbances in genetically predisposed individuals and physicians should be aware of this possible association.

High immunogenicity of delayed third dose of hepatitis B vaccine in travellers

Travellers often present late for the third dose of hepatitis B vaccination and measuring anti-HBs serology is common practice to ensure that these individuals are protected. We assessed the adequacy of immune response in 86 healthy travellers who had their third dose of hepatitis B (HB) vaccine performed more than 1 year (median: 3.4 years; range: 1.1–10.5 years) after the second dose. Eighty-two travellers (95.3%) had evidence of sero-protection (anti-HBs titre >10 UI/L) including 16/17 (94.1%) travellers who had an interval of more than 5 years between second and third vaccine dose. We did not find any risk factor associated with insufficient response.

Assessment of Delay in Age-appropriate Vaccination Using Survival Analysis

Assessment of delay in age-appropriate vaccination provides more information about timeliness of vaccination than up-to-date vaccination coverage. The authors applied survival analysis methods to data from a vaccination coverage survey among children aged 13-59 months conducted in Argentina in 2002. By age 19 months, 43% of children (95% confidence interval (CI): 40, 46) were vaccinated with the fourth dose of diphtheria, tetanus, and pertussis (DTP4). By age 13 months, 55% of children (95% CI: 52, 57) were vaccinated with measles-containing vaccine. By age 7 months, 33% of children (95% CI: 27, 40) were vaccinated with the third dose of hepatitis B. Compared with firstborn children, third children were more likely to be delayed for DTP4 (relative risk (RR) = 1.41, 95% CI: 1.22, 1.62), measles-containing vaccine (RR = 1.54, 95% CI: 1.32, 1.78), and the third dose of hepatitis B (RR = 1.31, 95% CI: 1.03, 1.67). Children whose caregivers had completed secondary school were less likely to be delayed for DTP4 (RR = 0.68, 95% CI: 0.52, 0.90) compared with those whose caregivers had not completed primary school. Survival analysis methods were helpful in measuring vaccine uptake and should be considered in future surveys when assessing delay in age-appropriate vaccination.

Vaccination coverage in the South-East Anatolian Project (SEAP) region and factors influencing low coverage

To determine the vaccination coverage of children living in the South-east Anatolian Project (SEAP) region; whether the vaccination coverage was similar to formal reports, other studies and other countries; and which factors influence vaccination, in order to indicate how vaccination coverage can be improved. A descriptive cross-sectional study conducted in nine provinces of the SEAP region in order to determine public health problems and their causes. A population-based sample of 1150 houses was selected from rural and urban areas of the SEAP region and visited by the researchers. Questionnaires were applied in 2001 and 2002. In the SEAP region, only 30% of children had received a complete set of vaccines. The vaccination coverage was 76.7% for Bacille Calmette-Guérin; 62.0% for the third doses of diphtheria, tetanus toxoid, pertussis and polio vaccine; 62.7% for measles; 44% for the third dose of hepatitis B vaccine in children aged 12-23 months; and 13.3% for the second dose of tetanus toxoid in women who gave birth in the last 5 years. In logistic regression analysis, residence type, number of siblings, birth interval, follow-up visits of midwives, and maternal level of education were found to influence whether children were completely vaccinated. The findings of this study indicate that vaccination coverage is not acceptable in the SEAP region. Efforts must focus on family planning services, education of women, follow-up visits and strengthening health facilities, especially in rural regions, to improve vaccination.

Recommended Childhood Immunization Schedule—United States, 2002

Since publication of the recommended childhood immunization schedule in January 1997, CDC's Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP) have changed recommended ages for administration of measles-mumps-rubella vaccine (MMR) and poliovirus vaccines. In addition, these organizations have clarified recommendations for administration of MMR, varicella vaccine, and hepatitis B vaccine during the routine visit to health-care providers for adolescents aged 11-12 years; the interchangeability of the three licensed Haemophilus influenzae type b (Hib) vaccines for primary and booster vaccination; and the timing for the third dose of hepatitis B vaccine. This report presents the recommended childhood immunization schedule for 1998 and explains the changes that have occurred since publication of the last schedule. Detailed recommendations about the use of vaccines are available from the manufacturers' package inserts, the 1997 Red Book, or ACIP statements on specific vaccines.

A simplified schedule to integrate the hepatitis B vaccine into an expanded program of immunization in endemic countries

Objective: To investigate the safety, immunogenicity, and efficacy of a simplified hepatitis B vaccination schedule. Methods: The second dose of hepatitis B vaccine and the first dose of diphtheria-tetanus-pertussis (DTP) vaccine were given simultaneously at age 6 weeks. The second dose of DTP vaccine was given at age 3.5 months. The third dose of DTP vaccine and the third dose of hepatitis B vaccine were given at age 5.5 months. One hundred three infants (group A) born to mothers without hepatitis B surface antigen (HBsAg) received DTP with whole-cell pertussis vaccine. Fifty-five infants (group B) born to mothers with HBsAg and hepatitis B e antigen received DTP with acellular pertussis vaccine. Results: By age 9 months, none of group A and 4 (7%) group B infants were seropositive for HBsAg. The protective efficacy against the hepatitis B carrier state in these infants at high risk was 92%. Antibody to hepatitis B surface antigen was 10 mIU/ml or greater in 99 (96%) of group A infants and in 50 (91%) of group B infants. Both the acellular and whole-cell DTP vaccines were immunogenic, and the incidences of adverse reactions were within an expected and acceptable range. Conclusions: The simplified vaccination schedule to integrate the hepatitis B vaccine into the Expanded Programme of Immunization was safe, immunogenic, and effective. This schedule may improve vaccine compliance and be applied to DTP and hepatitis B combination vaccines now under investigation. (J Pediatr 1997;130:981-6)

Compliance with immunization against hepatitis B. A pragmatic study in sexually transmitted disease clinics

The efficacy of a vaccine is based primarily on the adherence of the subject to the immunization schedule. This paper compares the compliance rates (CR) for the third dose of hepatitis B virus (HBV) vaccine given according to one of two vaccination schedules among subjects attending two sexually transmitted disease (STD) clinics, and the potential influence of place of vaccine administration (STD clinic or at a vaccination centre). Heterosexual, anti-HBc seronegative subjects (n=331) were randomized to a 0-1-6 month (n=i61) or a 0-1-2-12 month schedule (n=170) in this prospective, randomized, parallel pragmatic study. Some subjects (n=50) attended and were vaccinated at one STD clinic (centre A), whereas 281 attended another clinic (centre B) but were referred to a vaccination centre for administration of vaccine. About 31% (103331) of the subjects received at least three vaccine doses. On assessing the CR at the 3rd dose in all randomized subjects, we observed that administration of the vaccine at the STD clinic attended (A) was associated with a significantly better CR (p<0.01) than that of the subjects referred to a vaccination centre (B), while the CR is not affected by the schedule. On the other hand, the 0-1-2-12 schedule was associated with a significantly better CR (p=0.02) at the 3rd dose than the 0-1-6 month schedule among subjects who comply with the first two doses; the actual site of vaccine administration (in situ (A) versus referred (B)) does not affect the CR. On assessing the CR for the booster dose (month 12) in the 0-1-2-12 schedule, we observed that the CR is significantly better (p<0.001) if the vaccine is administered at the STD attending clinic (A) in all randomized subjects and among those who comply with the first three doses. We conclude that the CR could be increased by vaccinating all subjects at the STD clinic. Among those subjects who comply with the first two doses, the CR at the 3rd dose is better with the 0-1-2 schedule than with the 0-1-6 schedule. However, the need for administration of a booster dose (month 12) in the former schedule does not allow us to recommend this in preference to the latter.