D. Scott LaMontagne

Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middle-income countries

OBJECTIVE To assess human papillomavirus (HPV) vaccination coverage after demonstration projects conducted in India, Peru, Uganda and Viet Nam by PATH and national governments and to explore the reasons for vaccine acceptance or refusal. METHODS Vaccines were delivered through schools or health centres or in combination with other health interventions, and either monthly or through campaigns at fixed time points. Using a two-stage cluster sample design, the authors selected households in demonstration project areas and interviewed over 7000 parents or guardians of adolescent girls to assess coverage and acceptability. They defined full vaccination as the receipt of all three vaccine doses and used an open-ended question to explore acceptability. FINDINGS Vaccination coverage in school-based programmes was 82.6% (95% confidence interval, CI: 79.3-85.6) in Peru, 88.9% (95% CI: 84.7-92.4) in 2009 in Uganda and 96.1% (95% CI: 93.0-97.8) in 2009 in Viet Nam. In India, a campaign approach achieved 77.2% (95% CI: 72.4-81.6) to 87.8% (95% CI: 84.3-91.3) coverage, whereas monthly delivery achieved 68.4% (95% CI: 63.4-73.4) to 83.3% (95% CI: 79.3-87.3) coverage. More than two thirds of respondents gave as reasons for accepting the HPV vaccine that: (i) it protects against cervical cancer; (ii) it prevents disease, or (iii) vaccines are good. Refusal was more often driven by programmatic considerations (e.g. school absenteeism) than by opposition to the vaccine. CONCLUSION High coverage with HPV vaccine among young adolescent girls was achieved through various delivery strategies in the developing countries studied. Reinforcing positive motivators for vaccine acceptance is likely to facilitate uptake.

Sociocultural Issues in the Introduction of Human Papillomavirus Vaccine in Low-Resource Settings

OBJECTIVES (1) To synthesize sociocultural results from diverse populations related to vaccine decision-making, understanding of cervical cancer and its etiology, experience with previous vaccinations, human papillomavirus (HPV) vaccine concerns, and information needed to foster acceptance; (2) to contextualize findings in light of recent studies; and (3) to discuss implications for communication strategies to facilitate vaccine acceptance. DESIGN Descriptive qualitative synthesis of sociocultural studies in 4 countries using iterative theme-based analyses. SETTING Four developing countries: India, Peru, Uganda, and Vietnam. PARTICIPANTS Criterion-based sample of 252 focus-group discussions and 470 in-depth interviews with children, parents, teachers/administrators, health workers/managers, and community/religious leaders. A knowledge, attitudes, and practices survey was administered to 879 children and 875 parents in Vietnam. RESULTS We found that vaccine decision-making was primarily done by parents, with children having some role. Understanding of cervical cancer and HPV was limited; however, the gravity of cancer and some symptoms of cervical cancer were recognized. Vaccination and government-sponsored immunization programs were generally supported by respondents. Sentiments toward cervical cancer vaccines were positive, but concerns about quality of delivery, safety, adverse effects, and the effect on fertility were raised. Communities requested comprehensive awareness-raising and health education to address these concerns. CONCLUSION Sociocultural studies help elucidate the complexities of introducing a new vaccine from the perspective of children, parents, and communities. Strategies for introducing the HPV vaccine should address community concerns through effective communication, appropriate delivery, and targeted advocacy to make the program locally relevant.

Immunogenicity and Reactogenicity of Alternative Schedules of HPV Vaccine in Vietnam: A Cluster Randomized Noninferiority Trial

CONTEXT Human papillomavirus (HPV) vaccine programs may decrease the morbidity and mortality due to cervical cancer seen among women in low-resource countries. However, the 3-dose schedule over a 6-month period is a potential barrier to vaccine introduction in such settings. OBJECTIVE To determine the immunogenicity and reactogenicity of different dosing schedules of quadrivalent HPV vaccine in adolescent girls in Vietnam. DESIGN, SETTING, AND PARTICIPANTS Open-label, cluster randomized, noninferiority study (conducted between October 2007 and January 2010) assessing 4 schedules of an HPV vaccine delivered in 21 schools to 903 adolescent girls (aged 11-13 years at enrollment) living in northwestern Vietnam. INTERVENTION Intramuscular injection of 3 doses of quadrivalent HPV vaccine delivered on a standard dosing schedule (at 0, 2, and 6 months) and 3 alternative dosing schedules (at 0, 3, and 9 months; at 0, 6, and 12 months; or at 0, 12, and 24 months). MAIN OUTCOME MEASURES Serum anti-HPV geometric mean titers (GMT) measured 1 month after the third dose of the HPV vaccine was administered; GMT was determined by type-specific competitive immunoassay. Noninferiority of each alternative vaccination dosing schedule was achieved if the lower bound of the multiplicity-adjusted confidence interval (CI) of the type-specific GMT ratio for HPV-16 and HPV-18 was greater than 0.5 (primary outcome). Safety outcomes were immediate reactions, local reactions, fever within 7 days after each dose, and serious adverse events up to 30 days following the last dose. RESULTS In the intention-to-treat analysis, 809 girls who received at least 1 HPV vaccine dose had valid serum measurements 1 month after the third dose. After the third dose, the GMTs for those in the standard schedule group who received doses at 0, 2, and 6 months were 5808.0 (95% CI, 4961.4-6799.0) for HPV-16 and 1729.9 (95% CI, 1504.0-1989.7) for HPV-18; 5368.5 (95% CI, 4632.4-6221.5) and 1502.3 (95% CI, 1302.1-1733.2), respectively, for those whose received doses at 0, 3, and 9 months; 5716.4 (95% CI, 4876.7-6700.6) and 1581.5 (95% CI, 1363.4-1834.6), respectively, for those who received doses at 0, 6, and 12 months; and 3692.5 (95% CI, 3145.3-4334.9) and 1335.7 (95% CI, 1191.6-1497.3), respectively, for those who received doses at 0, 12, and 24 months. Noninferiority criteria were met for the alternative schedule groups that received doses at 0, 3, and 9 months (HPV-16 GMT ratio: 0.92 [95% CI, 0.71-1.20]; HPV-18 GMT ratio: 0.87 [95% CI, 0.68-1.11]) and at 0, 6, and 12 months (HPV-16 GMT ratio: 0.98 [95% CI, 0.75-1.29]; HPV-18 GMT ratio: 0.91 [95% CI, 0.71-1.17]). Prespecified noninferiority criteria were not met for the alternative schedule group that received doses at 0, 12, and 24 months (HPV-16 GMT ratio: 0.64 [95% CI, 0.48-0.84]; HPV-18 GMT ratio: 0.77 [95% CI, 0.62-0.96]). Pain at the injection site was the most common adverse event. CONCLUSIONS Among adolescent girls in Vietnam, administration of the HPV vaccine on standard and alternative schedules was immunogenic and well tolerated. The use of 2 alternative dosing schedules (at 0, 3, and 9 months and at 0, 6, and 12 months) compared with a standard schedule (at 0, 2, and 6 months) did not result in inferior antibody concentrations. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00524745.

Strategies to vaccinate against cancer of the cervix: feasibility of a school-based HPV vaccination program in Peru.

Operational research using a mixed method, cross-sectional, case-study approach assessed the feasibility and health system impact of large-scale implementation of human papillomavirus (HPV) vaccination into routine vaccine delivery by the Ministry of Health in Peru. The strategy was school-based vaccination of fifth grade girls in 527 primary schools in Piura region. Our evaluation showed that school-based HPV vaccination is feasible without major changes in existing health systems. This was reflected in the opinions of health personnel, the lack of impact on other vaccine coverage, and the high HPV vaccine coverage documented in routine records and by an independent community-based survey.

Delivery cost of human papillomavirus vaccination of young adolescent girls in Peru, Uganda and Viet Nam

OBJECTIVE To estimate the incremental delivery cost of human papillomavirus (HPV) vaccination of young adolescent girls in Peru, Uganda and Viet Nam. METHODS Data were collected from a sample of facilities that participated in five demonstration projects for hpv vaccine delivery: school-based delivery was used in Peru, Uganda and Viet Nam; health-centre-based delivery was also used in Viet Nam; and integrated delivery, which involved existing health services, was also used in Uganda. Microcosting methods were used to guide data collection on the use of resources (i.e. staff, supplies and equipment) and data were obtained from government, demonstration project and health centre administrative records. Delivery costs were expressed in 2009 United States dollars (US

Acceptance patterns and decision-making for human papillomavirus vaccination among parents in Vietnam: an in-depth qualitative study post-vaccination

). Exclusively project-related expenses and the cost of the vaccine were excluded. FINDINGS The economic delivery cost per vaccine dose ranged from US

Health systems and immunization financing for human papillomavirus vaccine introduction in low-resource settings

1.44 for integrated outreach in Uganda to US

Immunogenicity of Quadrivalent HPV Vaccine Among Girls 11 to 13 Years of Age Vaccinated Using Alternative Dosing Schedules: Results 29 to 32 Months After Third Dose

3.88 for school-based delivery in Peru. In Viet Nam, the lowest cost per dose was US

Influences on parental acceptance of HPV vaccination in demonstration projects in Uganda and Vietnam.

1.92 for health-centre-based delivery. Cost profiles revealed that, in general, the largest contributing factors were project start-up costs and recurrent personnel costs. The delivery cost of HPV vaccine was higher than published costs for traditional vaccines recommended by the Expanded Programme on Immunization (EPI). CONCLUSION The cost of delivering HPV vaccine to young adolescent girls in Peru, Uganda and Viet Nam was higher than that for vaccines currently in the EPI schedule. The cost per vaccine dose was lower when delivery was integrated into existing health services.

Parental acceptance of HPV vaccine in Peru: a decision framework.

BackgroundThe GAVI Alliance’s decision in late 2011 to invite developing countries to apply for funding for human papillomavirus (HPV) vaccine introduction underscores the importance of understanding levels of HPV vaccine acceptance in developing country settings. In this paper, we present findings from qualitative research on parents’ rationales for vaccinating or not vaccinating their daughters (vaccine acceptance) and their decision-making process in the context of an HPV vaccination demonstration project in Vietnam (2008–2009).MethodsWe designed a descriptive qualitative study of HPV vaccine acceptability among parents of girls eligible for vaccination in four districts of two provinces in Vietnama. The study was implemented after each of two years of vaccinations was completed. In total, 133 parents participated in 16 focus group discussions and 27 semi-structured interviews.ResultsFocus group discussions and in-depth interviews with parents of girls vaccinated revealed that they were generally very supportive of immunization for disease prevention and of vaccinating girls against HPV. The involvement of the National Expanded Program of Immunization in the demonstration project lent credibility to the HPV vaccine, contributing to high levels of acceptance. For parents who declined participation, concerns about side effects, the possibility that the vaccine was experimental, and the possible impact of the vaccine on future fertility rose to the surface. In terms of the decision-making process, many parents exhibited ‘active decision-making,’ reaching out to friends, family, and opinion leaders for guidance prior to making their decision.ConclusionVietnam’s HPV vaccination experience speaks to the importance of close collaboration with the government to make the most of high levels of trust, and to reduce suspicions about new vaccines that may arise in the context of vaccine introduction in developing country settings.