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Health systems and immunization financing for human papillomavirus vaccine introduction in low-resource settings
Vaccine 27 (2009) 6203–6209
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Vaccine journal homepage: www.elsevier.com/locate/vaccine
Health systems and immunization financing for human papillomavirus vaccine introduction in low-resource settings Robin Biellik a , Carol Levin b , Emmanuel Mugisha c , D. Scott LaMontagne b,∗ , Allison Bingham b , Satish Kaipilyawar d , Sanjay Gandhi e a
PATH, Tranchepied 10, 1278 La Rippe, Switzerland PATH, 1455 NW Leary Way, Seattle, WA 98107-5136, USA PATH, 1st Floor, Plot 6 (WHO Building), Hannington Road, Kampala, Uganda d PATH, 2nd Floor, State Immunization Complex, Commissionerate of Family Welfare, DM&HS Campus, Sultan Bazaar, Koti, Hyderabad, Andhra Pradesh 500 095, India e PATH, 351, Solitaire Corporate Park, Chakala, Andheri East, Mumbai 400 093, India b c
a r t i c l e
i n f o
Article history: Received 2 April 2009 Received in revised form 22 July 2009 Accepted 2 August 2009 Available online 19 August 2009 Keywords: HPV vaccine Health system Vaccine delivery
a b s t r a c t This descriptive qualitative study synthesizes health system and immunization financing assessments performed through formative research in India, Peru, Uganda, and Vietnam using a non-probability sample of national and sub-national stakeholders; and recommends appropriate and effective strategies for HPV vaccine delivery in low-resource settings. We conclude that maximum feasibility and acceptability and lowest cost for delivering HPV vaccine can be achieved by implementing through national immunization programs; by partnering with other sectors, such as education and maternal–child health; by strengthening existing human resources and cold chain infrastructures where needed; and finally, by considering schools for reaching the target population. © 2009 Elsevier Ltd. All rights reserved.
1. Introduction Two commercially available vaccines against human papillomavirus (HPV) have been shown to be safe and effective against the most common oncogenic HPV types 16 and 18 [1–4], which account for 70% of cervical cancer cases worldwide [5,6]. Clinical trial data suggest the vaccines work best when administered to women who are naïve to HPV sub-types in the vaccines, which implies prior to the onset of sexual activity [4]. For this reason, national advisory bodies generally recommend that young female adolescents aged 10–14 years be considered as the primary target group to receive the vaccines [7,8]. Recent articles have suggested particular challenges in delivering the HPV vaccines to girls in this age group because they are not the focus of traditional infant and child immunization program models and may be difficult to reach if they do not attend school [7,9,10]. The World Health Organization (WHO) has noted that successful planning for new vaccine introduction in developing-country settings requires an integrated and comprehensive approach that addresses individual and community factors for acceptance, insti-
∗ Corresponding author at: PATH, Reproductive Health, 1455 NW Leary Way, Seattle, WA 98107-5136, USA. Tel.: +1 206 285 3500; fax: +1 206 285 6619. E-mail address: [email protected] (D.S. LaMontagne). 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.08.003
tutional and infrastructure needs for appropriate and effective vaccine delivery, and the policy environment for political and financial support of the new vaccine [11]. Formative studies can be a critical first step by gathering empirical data to inform advocacy and the introduction process [12]. PATH recently completed formative research related to HPV vaccine introduction in four countries—India, Peru, Uganda, and Vietnam—as a part of the larger 5-year HPV Vaccines: Evidence for Impact project, which aims to generate evidence for decision-making and operational planning relevant to HPV vaccine introduction in low-resource settings [13]. Our formative research studies investigated three interrelated components for each country: (1) the sociocultural milieu—i.e., the social and cultural context of health and well-being that may influence support for HPV vaccination; (2) the health system structure—those institutional factors affecting successful vaccine delivery; and (3) the policy environment—structures and processes required for policy formulation for HPV vaccine introduction [14]. This paper synthesizes data from the health system structure component of the formative research. We describe each individual health system and immunization financing structure, comparing similarities and differences across the four project countries, and discuss the implications of these results in designing effective strategies for HPV vaccine delivery.
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2. Methods We designed a qualitative study that synthesized the health system components from formative research implemented in four developing countries [14–19]. In brief, the formative research was conducted from 2006 to 2008 by multidisciplinary teams in each country, and employed a qualitative, interdisciplinary, team-based approach, guided by an ecological conceptual framework [12,20]. The ecological framework adapted for HPV vaccine introduction consisted of five levels of influence—individual, interpersonal, community, institutional, and policy—that formed the basic units of analysis and defined the key target groups for comparability across sites [14]. The full methodology for the entire body of formative research and for country-specific research are being reported elsewhere [14,21,22]. 2.1. Site selection Research locations were selected based on ethnic/linguistic diversity, topographic diversity, socioeconomic characteristics, school attendance, documented experience with vaccination, and urban/rural representation. Each country research team also employed its own criteria for site selection that were locally relevant [14–19,21,22]. For example, in India, the formative study was conducted in one district in each of two selected states (Khammam in Andhra Pradesh state and Vadodara in Gujarat state) and the district selection was based on the proportion of married girls younger than 18 years, the percentage of children aged 12–35 months who were fully vaccinated, the proportion of women visited by an auxiliary nurse midwife (ANM)/health worker, the literacy rate, and the school dropout rate in grades 1–5 [15,22]. 2.2. Study populations The criteria which guided sampling in all countries aimed to engage the appropriate stakeholders required to assess country readiness for HPV vaccine introduction, according to the conceptual framework described in Ref. [14] and to obtain a wide range of experiences in order to capture the greatest variability [14,23]. Groups were selected purposively to represent a wide diversity of opinion and experience related to vaccine delivery. The study populations for the health system component included users of vaccination services (individual level); community and civic leaders (community level); teachers, head teachers and education staff, and local, district, and regional health professionals (institutional level); and political and technical leaders at national and sub-national levels (policy level) (Table 1) [15–19,21]. 2.3. Data collection and sources This study used data from comprehensive country-level technical reports of the formative research [15–19]. Data collection included focus group discussions, in-depth interviews, exit interviews of mothers utilizing immunization services, desk reviews of relevant immunization program documents, vaccination services observations, health facility records reviews, cold chain assessments, and workshops or consultations of immunization experts (Table 1). To complement these data, a rapid assessment of current and future immunization financing was conducted through consulting existing literature, interviewing key stakeholders at the central and local levels, and analyzing secondary data from country financial sustainability plans and comprehensive multiyear plans. Methods were combined as appropriate to each country setting in order to build upon and complement each other. The health system component of the formative research is based on data collected regarding the existing health services, covering
any specifically targeted young adolescents, and the current immunization program service delivery. Information was collected on human resources, health information systems, financing mechanisms, logistics and cold chain capacity for vaccine transport and storage, and possible strategies that might be most effective for HPV vaccine delivery. 2.4. Analysis of data Our synthesis utilized a general inductive approach [23–25] for which topics were developed from the formative research objectives, based on prominent health system and immunization topics noted in the vaccine research literature [7,10,11,26,27]. These topics were further validated in a 2007 workshop where country research teams highlighted these six themes as the most useful for HPV vaccine health system pre-introduction planning [14]. The technical reports were treated as textual data. Researchers carried out repeated inductive analysis using multiple iterative reviews of the reports to summarize key findings. Text segments related to each topic were pulled from each report by one researcher and organized according to topic covered. Further analysis by country was then conducted on data from each topic. The analysis was verified by at least three to four other researchers who were on the country-level health system study teams. Results are presented according to the six key topics explored: (1) health services for young adolescents; (2) current immunization systems; (3) immunization financing; (4) vaccine logistics and cold chain systems; (5) health information systems and human resources; and (6) effective delivery strategies for the HPV vaccines. 3. Results Across the four project countries, a total of 53 focus group discussions, 374 in-depth or key informant interviews, 4 consultations with immunization experts, and 45 exit interviews with users of vaccination services were conducted; these were supplemented by 10 facility assessments and 11 observations of vaccination sessions (Table 1). 3.1. Health services for young adolescents All the four countries included in our research indicated that certain health services were available to older female adolescents, defined roughly as 15 years of age and older. These services were generally free of charge and involved reproductive health care. There are, however, some programs that also serve younger adolescents. For example, the most prominent nationwide programs covering female adolescents in India were the Kishore Balika Scheme and the Kishori Shakti Yojana component of the Integrated Child Development Scheme implemented by the Ministry of Health, which is a social initiative for the development and empowerment of girls aged 11–18 years involving a range of “healthy living” interventions. Uganda utilized a different delivery mechanism—Child Days Plus or CDP (previously Child Health Days)—to reach children and adolescents of varying ages for health services. These events are programmed twice yearly, usually in April and October, and use a variety of venues, including health facilities, schools, churches, community centers, and government offices, to deliver tetanus toxoid (TT) or other catch-up vaccinations, vitamin A supplementation, de-worming with antihelminthics, and so forth. For younger adolescent populations (less than 15 years of age), the prominent health service was vaccination. The service mix and eligibility age for national vaccination campaigns varied according to national guidelines for specific diseases. For example, in India, mass Japanese encephalitis (JE) campaigns have targeted children
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Table 1 Study groups and data collection methods by study country, 2007–2008. India
Peru
Uganda
Vietnam
Education sector
Teachers: 17 FGDs Head teachers: 3 IDIs
Teachers/head teachers: 1 FGD Teachers/head teachers: 72 IDIs
Teachers: 16 FGDs
Education staff: 22 IDIs
Health sector
Health workers: 10 FGDs
Health authorities, providers: 44 IDIs
Cold chain technicians/EPI focal persons: 11 KIs Health providers: 19 KIs
EPI staff: 11 IDIs
Immunization expert workshop: 1
District/commune health leaders: 8 IDIs EPI users: 23 IDIs
Civil society groups: 16 IDIs
Community leaders: 9 FGDs Local councilors, opinion leaders, health/education officials: 40 KIs
Women’s union leaders: 14 IDIs
Health policymakers: 17 IDIs
N/A
National/regional EPI leaders: 3 IDIs
Health administrators: 18 IDIs
Civil society
Facility assessments: 10 assessments Vaccination session observations: 11 sessions Exit interviews with users: 45 users Immunization expert consultations: 3 consultations Community leaders: 11 IDIs Opinion (religious) leader: 5 IDIs
Cold chain/vaccine stores staff: 12 IDIs
Local NGO: 4 IDIs Policy sector
Policy maker: 12 IDIs Policy influencers: 9 IDIs
Note: FGD, focus group discussion; IDI, in-depth interview; KI, key informant interview; EPI, expanded program on immunization; N/A, not applicable.
and adolescents 1–15 years of age; similarly, in Peru, the mass measles–rubella (MR) vaccination campaign in 2006 and the yellow fever (YF) vaccination campaign in 2006–2007 extended delivery to all children aged 14 years and younger. Campaigns were one-time events. School settings were used by all the four countries to deliver limited health services, but completeness and frequency varied
enormously. Vietnam has a full-time school health program that provides ophthalmic and dental check-ups, HIV/AIDS prevention, drug abuse prevention, reproductive health care, parasite control, traffic safety, and scoliosis screening. TT vaccination in schools was reported by all countries, but the timing and target population varied: in Vietnam, TT was an annual campaign to 15-year-old girls; in India, TT was provided annually to children in 4th and 10th stan-
Table 2 Antigens delivered, vaccination schedules and target age groups, four study countries, 2006.a .
Surviving infants (1000s) Vaccinesb
India
Peru
Uganda
Vietnam
25,640
570
1294
1621
India c
Infants <1 y BCG DPT DPT–HepB–Hib HepB Hib OPV Measles MR Other age groups DPT DT JE (selected areas) YF (selected areas) Measles Typhoid (selected areas) TT Td
Peru Age
Coverage
Age
Coverage
Agec
Coveraged
Birth 6 w, 10 w, 14 w
78% 55%
85%
Birth 2 m, 3 m, 4 m
95% 94%
6 w, 10 w, 14 w
80%
6%
Birth, 2 m, 4 m
93%
6 w, 10 w, 14 w 9–12 m
58% 59%
99% 94% 94% NR NR 95%
Birth
6 w, 10 w, 14 w (selected areas)
Birth 3m 2 m, 4 m Birth 3m 2 m, 3 m, 4 m
2 m, 3 m, 4 m 9m
94% 93%
12 m
99%
0e , +2 m, +4 m
NR 1 y, +2 w, +1 y
NR
1y
NR 6y 5y CBAWg
NR NR 88%
10 y, 16 y, pregnancyf
d
c
Vietnam
Coverage
NR NR NR
c
Uganda
Age
16–24 m 5y 1–2 y
d
6 w, 10 w, 14 w 9m
CBAWg
86% CBAWg
d
81% 89%
88%
82%
NR, not reported separately. a Source: WHO Vaccine Preventable Diseases Monitoring System, 2008 Global Summary. b Vaccines: BCG, bacillus Calmette–Guerin; DPT, diphtheria, pertussis, tetanus; HepB, hepatitis B; Hib, Haemophilus influenzae B; OPV, oral poliovaccine; MR, measles–rubella; JE, Japanese encephalitis; TT, tetanus toxoid; YF, yellow fever. c Recommended age of administration: w: weeks, m: months; y: years. d WHO-United Nations Children’s Fund best estimate of the percentage of target age group vaccinated (if >1 dose, last dose in series). e First contact among children >5 y (age at which pertussis vaccine is contraindicated). f Two doses in each pregnancy. Coverage reported as percent “protected at birth against tetanus.” g CBAW, child-bearing age women: first contact, +1 m, +6 m, +1 y, +1 y. Coverage reported as percent “protected at birth against tetanus.”
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Table 3 Immunization financing indicators in India, Peru, Uganda, and Vietnam. Country
Health expenditure as a percentage of GDPa
Immunizations as a percentage of total health expenditurea
Cost per fully immunized childb , c
India Peru Uganda Vietnam
5.0% 4.5% 7.6% 5.0%
<1% <1% <1% <1%
US$ 12–20 US$ 20 US$ 21 US$ 7.39
a Source: WHO National Health Accounts (http://www.who.int/nha/country/ Regional Averages by WB Income group-En.xls). b Reflects costs for basic six antigens (BCG, DPT, OPV and measles vaccines). Hepatitis B vaccine is available in different presentations (mono-, tetra- and pentavalent). c These figures were estimated from the formative research technical reports [14–19].
dards (approximately 10 and 16 years old, respectively); in Peru, TT was combined with diphtheria and given as an annual campaign in the high schools to girls 15 years of age and older; and in Uganda, a pilot program for girls 12 years of age and older was reported, but implementation had yet to begin. 3.2. Current immunization systems Each country reported well-established systems for immunizations, based on WHO’s Expanded Programme on Immunization (EPI). Antigens provided, targeted age groups, and vaccination schedules were fairly consistent across countries (Table 2). Programs broadly distinguished between those targeting infants less than 1 year of age and those targeting children older than 1 year, adolescents, and adults, and varied according to local disease control priorities. With few exceptions, EPI services were delivered by trained health workers at specific health facilities and outreach sites. Vaccination coverage achievements in the four countries also varied, with the lowest coverage reported from India and the highest reported from Peru (Table 2). 3.3. Immunization financing Current expenditure levels on health and immunization varied across the four country sites, as did the sources of funding to support investments in health (Table 3). Expenditures on health as a share of gross domestic product (GDP) ranged from 4.5% in Peru to 7.6% in Uganda.1 Typically, less than 1% of total health expenditure was spent on routine immunization, and only slightly more when special campaigns were implemented [25]. India and Peru financed their EPI programs almost exclusively from internal government resources, while Vietnam and Uganda financed 25% and 50% of their programs, respectively, from external sources, such as the GAVI Alliance or other donors. The cost per fully immunized child ranged from just more than US$ 7 to US$ 21, depending on the presentation of the six core antigens2 and the inclusion of hepatitis B and Haemophilus influenzae B vaccines. Immunization budgets have increased significantly in three of the project countries, but only modestly for Vietnam (Table 3). We found differences in the allocation of program costs for immunization services between countries that were decentralized and those with more centralized implementation of their programs.
1 According to WHO National Health Accounts, the average health expenditure as a percentage of GDP is 4.1% for low-income countries and 11.2% among highincome countries (http://www.who.int/nha/country/Regional Averages by WB Income group-En.xls). 2 Hepatitis B vaccine had varying presentations across the countries. For example, it was given as a stand-alone vaccination to infants in India, but is one of the components of the pentavalent vaccine used in Uganda.
In decentralized systems, such as Vietnam, a larger proportion of program costs, especially those related to local personnel, transport, and maintenance of the cold chain were covered by local governments. In centrally sponsored immunization schemes, such as India, state governments contributed the majority of costs to the overall public health expenditure, which included paying vaccinator salaries as well as paying for cold chain and logistics costs. Decision-makers interviewed noted the challenges of co-financing obligations for supporting program costs, as well as vaccine copayments, if the HPV vaccines were introduced in the public sector. 3.4. Vaccine logistics and cold chain systems Structures and processes for vaccine delivery, transport, and storage were broadly similar across project countries, reflective of currently recommended EPI standards [26,27]. Except for India, where the vaccines were delivered by manufacturers directly to regional vaccine stores in each state, the project countries received the vaccines at national vaccine storage facilities. Vaccine distribution occurred from national stores to provincial or regional stores, then to district stores, with final distribution to health facilities occurring via cold boxes or vaccine carriers with preconditioned icepacks. Health facilities with refrigerators functioning at an appropriate temperature (+2 ◦ C to +8 ◦ C) and constant energy supplies sometimes operated as storage facilities. Vaccine distribution was implemented in accordance with the user rates and storage capacity. Respondents agreed that before introducing a new vaccine such as HPV, a systematic cold chain inventory was necessary to establish whether excess storage capacity existed to accommodate the additional volume. All the four project countries identified some excess cold chain capacity: India reported the greatest excess capacity at state level; Uganda reported the least excess capacity in national stores; and Peru noted no excess capacity and suggested the greatest need was at the local level. Uganda and Vietnam noted some refrigerators were out-ofservice and required repair. Shortages of liquid propane gas and cylinders were mentioned as a potential barrier to HPV vaccine introduction in Uganda. In Vietnam, many health facilities in mountainous regions lacked refrigerators; if existent, they were often domestic models that could not sustain an adequate storage temperature. This resulted in dependency on cold boxes, vaccine carriers, and frozen icepacks, which were in short supply. Lastly, human resources required specifically for cold chain and logistics management were reported to be limited in Gujarat state (India) and Vietnam, but not in Peru or Uganda. Additional staff to manage vaccine distribution may be needed if HPV vaccine were introduced. 3.5. Health information systems and human resources Each national EPI provided a client-retained vaccination card to record when vaccinations were administered to infants and pregnant women. Each program collected and analyzed vaccination coverage data. In all the four project countries, vaccination coverage data were collected through daily vaccination session tally sheets, consolidated upward through district and provincial/regional levels to the national level to generate coverage estimates. Computerization of data collection varied across countries, and was most often found at higher levels (e.g., national, regional, and district). Each project country also maintained a system for detecting, reporting, and investigating any reported or suspected serious adverse events following immunization (AEFI). Respondents noted government sensitivity to the negative publicity associated with reported AEFIs, regardless of causal association. Current mech-
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anisms for monitoring AEFIs and coverage were reported to be adequate should HPV vaccine be introduced into the national program. All countries stressed the need for additional training on HPV vaccines and cervical cancer, if HPV vaccine introduction occurred. Information on cervical cancer, its causes, risk factors, prevention, and HPV vaccine was lacking among many health professionals interviewed—who would be expected to be primary and secondary influencers for HPV vaccine efforts. 3.6. Effective delivery strategies for the HPV vaccines Respondents included in the health system component weighed the advantages and disadvantages of various delivery strategies for the HPV vaccines, bearing in mind their current systems, cold chain and storage capacities, and the target population of 10- to 14year-old girls. In all the four project countries, there was consensus that the EPI represents potentially the most effective mechanism for delivering the HPV vaccines, in view of its established national reputation, infrastructure, and well-trained human resources. Full integration of the HPV vaccines into routine vaccine service delivery through fixed health facilities and mobile teams serving outreach sites was generally not considered viable by health workers and technical staff at the district level in India, Peru, and Uganda. This was primarily because of concerns about the impact on the workload of health workers and the potential difficulty in getting mothers to bring girls of this age to the clinics. However, in Vietnam, where a longstanding, well-established, and well-attended system of vaccine delivery at fixed health centers was reported, respondents suggested the HPV vaccines could be integrated into the routine system. A campaign approach for HPV vaccine delivery was discussed initially, due to perceived synergies with age groups already targeted for JE, YF, or measles vaccination campaigns. However, when examined more closely, the three-dose HPV vaccine schedule and the single-dose annual campaign schedules were not compatible. A school-based strategy was identified by the majority of respondents in all the four project countries as being the most convenient and effective way of reaching 10- to 14-year-old girls, as the majority of girls in this age group were easily accessible at school. Initiatives, such as the Universal Primary Education policy in Uganda, have resulted in school enrollment increases [28], and were mentioned by respondents as justification for school-based delivery of the HPV vaccines. In India, vaccinating continuously in schools (every month) versus at fixed times according to the three-dose schedule for HPV was discussed. In Peru and Uganda, the advantages and disadvantages of vaccinating girls in school by age or by grade/class were considered. Vaccinating by age was seen as more challenging logistically, as some girls may not know their exact age. Despite the fairly wide age range in grades/classes in rural schools, arising from children starting school late and/or repeating grades, the logistic simplicity of vaccinating a single grade appealed to most health workers and technical staff at the district level. Generally, integration of HPV vaccination with adolescent health services or cervical cancer screening and treatment services was not considered a feasible approach. However, in Uganda, health policymakers and program managers strongly supported the idea of integrating HPV vaccine into CDP. This program was noted to be well-established, enjoyed a high level of community acceptance, and incorporated mechanisms for reaching out-ofschool girls. Funding earmarked from the national health budget and organized roles and responsibilities within communities were mentioned as facilitators to making this delivery approach effective. In India, linking HPV vaccination with existing TT vaccination or vitamin A distribution was suggested as a possible integrated
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delivery mechanism that could also be supplemented by health and hygiene education for girls. In this way, HPV vaccinations were considered a vehicle to strengthen other services as well as add new services for this population. 4. Discussion Our study of the health system and immunization financing structures in four developing countries sought to explore opportunities and challenges for future HPV vaccine introduction that may be particularly unique to these low-resource settings. The themes explored were similar to those considered most relevant for new vaccine introduction [11]. Using a mixed-method approach employing qualitative and quantitative techniques combined with literature and program document review, we hoped to elucidate the breadth of the concerns that may be broadly applicable to other developing countries. To this end, what are the implications of our results for effective HPV vaccine delivery strategies in these settings? Health services specifically targeted to younger adolescents, 10–14 years of age, are sparse, not routine, and if they do occur, are usually one-time interventions, such as distribution of vitamin A or antihelminthics or mass vaccination campaigns. The current immunization systems are robust and incorporate common elements for vaccine delivery recommended by WHO, such as age-appropriate vaccine schedules, health infrastructures and technical guidelines for human resources, vaccine logistics and cold chains, AEFI monitoring, and data collection and analysis, to achieve high levels of vaccination coverage [26,27]. Expenditures for these systems represent a very small fraction (<1%) of the total health expenditures in all the four countries. In each country, experience with providing health services in the school setting affords an opportunity for successful HPV vaccine delivery. Recent publications have suggested potential barriers or challenges to HPV vaccine delivery that are not borne out by the results of our study [7,9]. WHO has suggested that delivery of HPV vaccine to the 9- to 13-year-old age group will be particularly challenging because they are not normally included in country EPI programs, and school-based delivery schemes may be limited for this age group due to nonattendance or low attendance [7]. However, the respondents in our study noted that country EPI programs were best placed to deliver HPV vaccine given their expertise with the appropriate system support. Needs identified to strengthen the cold chain and health system infrastructure [9] included increasing refrigerator capacity at local levels (especially important if vaccine was supplied as single-dose vials and if other new vaccines will soon be introduced as well), replacing nonfunctioning equipment, ensuring adequate supply of fuel, and providing additional training to health workers. Brabin et al. [29] suggests the sexual nature of HPV infection would affect recommendation of HPV vaccine by health providers, and Paavonen and Lehtinen [30] argue that the gender-specific nature of a vaccine for a sexually transmitted infection may present difficulties. However, the sexual component of HPV transmission dynamics was rarely mentioned by our study respondents. This could reflect a bias in our data collection, as we contextualized HPV vaccine as cervical cancer prevention; however, as Bingham et al. [31] and Katahoire et al. [21] conclude, communication messages focusing on HPV vaccine as a preventive measure against cervical cancer may result in broader acceptability of the vaccine at all levels—parents, health workers, teachers, and policymakers. Challenges exist with a school-based delivery approach. The timing of the school year is fixed and the dosing schedule for HPV spans 6 months; thus, careful planning will be required to ensure all the three doses are delivered during one school year while accommodating vacation and examination schedules [32]. Typical
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vaccine delivery schedules use age as a selection basis for those eligible, but in schools, a grade-based delivery approach may be more efficient. Respondents from Uganda noted a wide age range for girls in some grades. Effective mechanisms for reaching outof-school girls will need to be considered for any school-based delivery program [7], as was mentioned by respondents from India. Despite these challenges, delivering the HPV vaccines at school may provide an opportunity to link other health interventions [9] (a sentiment expressed by many study respondents and a recommendation encouraged by WHO [7]), and also may provide a catalyst to encourage partnerships between health and education, reproductive health and immunization, and other key stakeholders [7]. Finally, any delivery program must be adequately supported financially, not just for the supply of vaccine, but also for the operational costs. The feasibility and sustainability of an HPV vaccination program will depend on the vaccine price and the supporting program costs to introduce HPV vaccine, within the context of overall health financing and specific immunization multiyear plans and projected budgets. We have seen in our results that in the past decade, there has been a trend of increasing immunization financing. This renewed interest in immunization program support from a financial perspective can be harnessed to advocate effectively with policymakers to consider full or partial co-funding to support HPV vaccine introduction [33]. While our summary provides practical information about health systems for HPV vaccine introduction in low-resource settings, there are some limitations to be noted. We synthesized data included in comprehensive technical reports from our formative research, rather than analyzing the original raw data from focus group discussions, in-depth interviews, vaccine session observations, immunization expert workshops, and exit interviews with mothers. Therefore, our study relied on culling major themes that were previously identified. Additionally, while our theme-based analysis approach was an inductive process recommended for qualitative data [24,34], we could not discern whether missing data were not collected or just not reported in the research report. Third, the countries included in this study were selected based on their representativeness of the region, burden of cervical cancer, health system infrastructure, and potential to adopt the HPV vaccines, but they may not be fully representative of all low-resource areas. Lastly, the study populations included in our research were purposively selected through a variety of techniques and were not systematically sampled for representativeness. 5. Conclusion Our findings suggest that low-resource settings may be able to successfully adopt the HPV vaccines, provided the health system structures and immunization financing options were well understood; the delivery strategy built off the existing strengths of national EPI programs with strong partnerships between other sectors, such as education, maternal–child health and reproductive health; system strengthening for effective vaccine delivery was supported; and schools could effectively be used as a venue in all the four countries. Overcoming institutional and implementation barriers will be key to program success. Demonstration projects to model routine delivery of HPV vaccine are being undertaken in all the four countries utilizing the findings from this research. Careful evaluation of those activities will reveal how well these qualitative findings predict actual practice. Acknowledgments Dr. Robin Biellik, lead author, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We wish to express our thanks
to the respective country governments, our colleagues, research partners, and study participants who contributed to the formative research studies in India, Peru, Uganda, and Vietnam. Special thanks to Dr. Vivien Tsu for her insightful comments to earlier drafts of this manuscript. Generous funding for this work was provided through a grant to PATH from the Bill & Melinda Gates Foundation.
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Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Health systems and immunization financing for human papillomavirus vaccine introduction in low-resource settings Robin Biellik a , Carol Levin b , Emmanuel Mugisha c , D. Scott LaMontagne b,∗ , Allison Bingham b , Satish Kaipilyawar d , Sanjay Gandhi e a
PATH, Tranchepied 10, 1278 La Rippe, Switzerland PATH, 1455 NW Leary Way, Seattle, WA 98107-5136, USA PATH, 1st Floor, Plot 6 (WHO Building), Hannington Road, Kampala, Uganda d PATH, 2nd Floor, State Immunization Complex, Commissionerate of Family Welfare, DM&HS Campus, Sultan Bazaar, Koti, Hyderabad, Andhra Pradesh 500 095, India e PATH, 351, Solitaire Corporate Park, Chakala, Andheri East, Mumbai 400 093, India b c
a r t i c l e
i n f o
Article history: Received 2 April 2009 Received in revised form 22 July 2009 Accepted 2 August 2009 Available online 19 August 2009 Keywords: HPV vaccine Health system Vaccine delivery
a b s t r a c t This descriptive qualitative study synthesizes health system and immunization financing assessments performed through formative research in India, Peru, Uganda, and Vietnam using a non-probability sample of national and sub-national stakeholders; and recommends appropriate and effective strategies for HPV vaccine delivery in low-resource settings. We conclude that maximum feasibility and acceptability and lowest cost for delivering HPV vaccine can be achieved by implementing through national immunization programs; by partnering with other sectors, such as education and maternal–child health; by strengthening existing human resources and cold chain infrastructures where needed; and finally, by considering schools for reaching the target population. © 2009 Elsevier Ltd. All rights reserved.
1. Introduction Two commercially available vaccines against human papillomavirus (HPV) have been shown to be safe and effective against the most common oncogenic HPV types 16 and 18 [1–4], which account for 70% of cervical cancer cases worldwide [5,6]. Clinical trial data suggest the vaccines work best when administered to women who are naïve to HPV sub-types in the vaccines, which implies prior to the onset of sexual activity [4]. For this reason, national advisory bodies generally recommend that young female adolescents aged 10–14 years be considered as the primary target group to receive the vaccines [7,8]. Recent articles have suggested particular challenges in delivering the HPV vaccines to girls in this age group because they are not the focus of traditional infant and child immunization program models and may be difficult to reach if they do not attend school [7,9,10]. The World Health Organization (WHO) has noted that successful planning for new vaccine introduction in developing-country settings requires an integrated and comprehensive approach that addresses individual and community factors for acceptance, insti-
∗ Corresponding author at: PATH, Reproductive Health, 1455 NW Leary Way, Seattle, WA 98107-5136, USA. Tel.: +1 206 285 3500; fax: +1 206 285 6619. E-mail address: [email protected] (D.S. LaMontagne). 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.08.003
tutional and infrastructure needs for appropriate and effective vaccine delivery, and the policy environment for political and financial support of the new vaccine [11]. Formative studies can be a critical first step by gathering empirical data to inform advocacy and the introduction process [12]. PATH recently completed formative research related to HPV vaccine introduction in four countries—India, Peru, Uganda, and Vietnam—as a part of the larger 5-year HPV Vaccines: Evidence for Impact project, which aims to generate evidence for decision-making and operational planning relevant to HPV vaccine introduction in low-resource settings [13]. Our formative research studies investigated three interrelated components for each country: (1) the sociocultural milieu—i.e., the social and cultural context of health and well-being that may influence support for HPV vaccination; (2) the health system structure—those institutional factors affecting successful vaccine delivery; and (3) the policy environment—structures and processes required for policy formulation for HPV vaccine introduction [14]. This paper synthesizes data from the health system structure component of the formative research. We describe each individual health system and immunization financing structure, comparing similarities and differences across the four project countries, and discuss the implications of these results in designing effective strategies for HPV vaccine delivery.
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2. Methods We designed a qualitative study that synthesized the health system components from formative research implemented in four developing countries [14–19]. In brief, the formative research was conducted from 2006 to 2008 by multidisciplinary teams in each country, and employed a qualitative, interdisciplinary, team-based approach, guided by an ecological conceptual framework [12,20]. The ecological framework adapted for HPV vaccine introduction consisted of five levels of influence—individual, interpersonal, community, institutional, and policy—that formed the basic units of analysis and defined the key target groups for comparability across sites [14]. The full methodology for the entire body of formative research and for country-specific research are being reported elsewhere [14,21,22]. 2.1. Site selection Research locations were selected based on ethnic/linguistic diversity, topographic diversity, socioeconomic characteristics, school attendance, documented experience with vaccination, and urban/rural representation. Each country research team also employed its own criteria for site selection that were locally relevant [14–19,21,22]. For example, in India, the formative study was conducted in one district in each of two selected states (Khammam in Andhra Pradesh state and Vadodara in Gujarat state) and the district selection was based on the proportion of married girls younger than 18 years, the percentage of children aged 12–35 months who were fully vaccinated, the proportion of women visited by an auxiliary nurse midwife (ANM)/health worker, the literacy rate, and the school dropout rate in grades 1–5 [15,22]. 2.2. Study populations The criteria which guided sampling in all countries aimed to engage the appropriate stakeholders required to assess country readiness for HPV vaccine introduction, according to the conceptual framework described in Ref. [14] and to obtain a wide range of experiences in order to capture the greatest variability [14,23]. Groups were selected purposively to represent a wide diversity of opinion and experience related to vaccine delivery. The study populations for the health system component included users of vaccination services (individual level); community and civic leaders (community level); teachers, head teachers and education staff, and local, district, and regional health professionals (institutional level); and political and technical leaders at national and sub-national levels (policy level) (Table 1) [15–19,21]. 2.3. Data collection and sources This study used data from comprehensive country-level technical reports of the formative research [15–19]. Data collection included focus group discussions, in-depth interviews, exit interviews of mothers utilizing immunization services, desk reviews of relevant immunization program documents, vaccination services observations, health facility records reviews, cold chain assessments, and workshops or consultations of immunization experts (Table 1). To complement these data, a rapid assessment of current and future immunization financing was conducted through consulting existing literature, interviewing key stakeholders at the central and local levels, and analyzing secondary data from country financial sustainability plans and comprehensive multiyear plans. Methods were combined as appropriate to each country setting in order to build upon and complement each other. The health system component of the formative research is based on data collected regarding the existing health services, covering
any specifically targeted young adolescents, and the current immunization program service delivery. Information was collected on human resources, health information systems, financing mechanisms, logistics and cold chain capacity for vaccine transport and storage, and possible strategies that might be most effective for HPV vaccine delivery. 2.4. Analysis of data Our synthesis utilized a general inductive approach [23–25] for which topics were developed from the formative research objectives, based on prominent health system and immunization topics noted in the vaccine research literature [7,10,11,26,27]. These topics were further validated in a 2007 workshop where country research teams highlighted these six themes as the most useful for HPV vaccine health system pre-introduction planning [14]. The technical reports were treated as textual data. Researchers carried out repeated inductive analysis using multiple iterative reviews of the reports to summarize key findings. Text segments related to each topic were pulled from each report by one researcher and organized according to topic covered. Further analysis by country was then conducted on data from each topic. The analysis was verified by at least three to four other researchers who were on the country-level health system study teams. Results are presented according to the six key topics explored: (1) health services for young adolescents; (2) current immunization systems; (3) immunization financing; (4) vaccine logistics and cold chain systems; (5) health information systems and human resources; and (6) effective delivery strategies for the HPV vaccines. 3. Results Across the four project countries, a total of 53 focus group discussions, 374 in-depth or key informant interviews, 4 consultations with immunization experts, and 45 exit interviews with users of vaccination services were conducted; these were supplemented by 10 facility assessments and 11 observations of vaccination sessions (Table 1). 3.1. Health services for young adolescents All the four countries included in our research indicated that certain health services were available to older female adolescents, defined roughly as 15 years of age and older. These services were generally free of charge and involved reproductive health care. There are, however, some programs that also serve younger adolescents. For example, the most prominent nationwide programs covering female adolescents in India were the Kishore Balika Scheme and the Kishori Shakti Yojana component of the Integrated Child Development Scheme implemented by the Ministry of Health, which is a social initiative for the development and empowerment of girls aged 11–18 years involving a range of “healthy living” interventions. Uganda utilized a different delivery mechanism—Child Days Plus or CDP (previously Child Health Days)—to reach children and adolescents of varying ages for health services. These events are programmed twice yearly, usually in April and October, and use a variety of venues, including health facilities, schools, churches, community centers, and government offices, to deliver tetanus toxoid (TT) or other catch-up vaccinations, vitamin A supplementation, de-worming with antihelminthics, and so forth. For younger adolescent populations (less than 15 years of age), the prominent health service was vaccination. The service mix and eligibility age for national vaccination campaigns varied according to national guidelines for specific diseases. For example, in India, mass Japanese encephalitis (JE) campaigns have targeted children
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Table 1 Study groups and data collection methods by study country, 2007–2008. India
Peru
Uganda
Vietnam
Education sector
Teachers: 17 FGDs Head teachers: 3 IDIs
Teachers/head teachers: 1 FGD Teachers/head teachers: 72 IDIs
Teachers: 16 FGDs
Education staff: 22 IDIs
Health sector
Health workers: 10 FGDs
Health authorities, providers: 44 IDIs
Cold chain technicians/EPI focal persons: 11 KIs Health providers: 19 KIs
EPI staff: 11 IDIs
Immunization expert workshop: 1
District/commune health leaders: 8 IDIs EPI users: 23 IDIs
Civil society groups: 16 IDIs
Community leaders: 9 FGDs Local councilors, opinion leaders, health/education officials: 40 KIs
Women’s union leaders: 14 IDIs
Health policymakers: 17 IDIs
N/A
National/regional EPI leaders: 3 IDIs
Health administrators: 18 IDIs
Civil society
Facility assessments: 10 assessments Vaccination session observations: 11 sessions Exit interviews with users: 45 users Immunization expert consultations: 3 consultations Community leaders: 11 IDIs Opinion (religious) leader: 5 IDIs
Cold chain/vaccine stores staff: 12 IDIs
Local NGO: 4 IDIs Policy sector
Policy maker: 12 IDIs Policy influencers: 9 IDIs
Note: FGD, focus group discussion; IDI, in-depth interview; KI, key informant interview; EPI, expanded program on immunization; N/A, not applicable.
and adolescents 1–15 years of age; similarly, in Peru, the mass measles–rubella (MR) vaccination campaign in 2006 and the yellow fever (YF) vaccination campaign in 2006–2007 extended delivery to all children aged 14 years and younger. Campaigns were one-time events. School settings were used by all the four countries to deliver limited health services, but completeness and frequency varied
enormously. Vietnam has a full-time school health program that provides ophthalmic and dental check-ups, HIV/AIDS prevention, drug abuse prevention, reproductive health care, parasite control, traffic safety, and scoliosis screening. TT vaccination in schools was reported by all countries, but the timing and target population varied: in Vietnam, TT was an annual campaign to 15-year-old girls; in India, TT was provided annually to children in 4th and 10th stan-
Table 2 Antigens delivered, vaccination schedules and target age groups, four study countries, 2006.a .
Surviving infants (1000s) Vaccinesb
India
Peru
Uganda
Vietnam
25,640
570
1294
1621
India c
Infants <1 y BCG DPT DPT–HepB–Hib HepB Hib OPV Measles MR Other age groups DPT DT JE (selected areas) YF (selected areas) Measles Typhoid (selected areas) TT Td
Peru Age
Coverage
Age
Coverage
Agec
Coveraged
Birth 6 w, 10 w, 14 w
78% 55%
85%
Birth 2 m, 3 m, 4 m
95% 94%
6 w, 10 w, 14 w
80%
6%
Birth, 2 m, 4 m
93%
6 w, 10 w, 14 w 9–12 m
58% 59%
99% 94% 94% NR NR 95%
Birth
6 w, 10 w, 14 w (selected areas)
Birth 3m 2 m, 4 m Birth 3m 2 m, 3 m, 4 m
2 m, 3 m, 4 m 9m
94% 93%
12 m
99%
0e , +2 m, +4 m
NR 1 y, +2 w, +1 y
NR
1y
NR 6y 5y CBAWg
NR NR 88%
10 y, 16 y, pregnancyf
d
c
Vietnam
Coverage
NR NR NR
c
Uganda
Age
16–24 m 5y 1–2 y
d
6 w, 10 w, 14 w 9m
CBAWg
86% CBAWg
d
81% 89%
88%
82%
NR, not reported separately. a Source: WHO Vaccine Preventable Diseases Monitoring System, 2008 Global Summary. b Vaccines: BCG, bacillus Calmette–Guerin; DPT, diphtheria, pertussis, tetanus; HepB, hepatitis B; Hib, Haemophilus influenzae B; OPV, oral poliovaccine; MR, measles–rubella; JE, Japanese encephalitis; TT, tetanus toxoid; YF, yellow fever. c Recommended age of administration: w: weeks, m: months; y: years. d WHO-United Nations Children’s Fund best estimate of the percentage of target age group vaccinated (if >1 dose, last dose in series). e First contact among children >5 y (age at which pertussis vaccine is contraindicated). f Two doses in each pregnancy. Coverage reported as percent “protected at birth against tetanus.” g CBAW, child-bearing age women: first contact, +1 m, +6 m, +1 y, +1 y. Coverage reported as percent “protected at birth against tetanus.”
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Table 3 Immunization financing indicators in India, Peru, Uganda, and Vietnam. Country
Health expenditure as a percentage of GDPa
Immunizations as a percentage of total health expenditurea
Cost per fully immunized childb , c
India Peru Uganda Vietnam
5.0% 4.5% 7.6% 5.0%
<1% <1% <1% <1%
US$ 12–20 US$ 20 US$ 21 US$ 7.39
a Source: WHO National Health Accounts (http://www.who.int/nha/country/ Regional Averages by WB Income group-En.xls). b Reflects costs for basic six antigens (BCG, DPT, OPV and measles vaccines). Hepatitis B vaccine is available in different presentations (mono-, tetra- and pentavalent). c These figures were estimated from the formative research technical reports [14–19].
dards (approximately 10 and 16 years old, respectively); in Peru, TT was combined with diphtheria and given as an annual campaign in the high schools to girls 15 years of age and older; and in Uganda, a pilot program for girls 12 years of age and older was reported, but implementation had yet to begin. 3.2. Current immunization systems Each country reported well-established systems for immunizations, based on WHO’s Expanded Programme on Immunization (EPI). Antigens provided, targeted age groups, and vaccination schedules were fairly consistent across countries (Table 2). Programs broadly distinguished between those targeting infants less than 1 year of age and those targeting children older than 1 year, adolescents, and adults, and varied according to local disease control priorities. With few exceptions, EPI services were delivered by trained health workers at specific health facilities and outreach sites. Vaccination coverage achievements in the four countries also varied, with the lowest coverage reported from India and the highest reported from Peru (Table 2). 3.3. Immunization financing Current expenditure levels on health and immunization varied across the four country sites, as did the sources of funding to support investments in health (Table 3). Expenditures on health as a share of gross domestic product (GDP) ranged from 4.5% in Peru to 7.6% in Uganda.1 Typically, less than 1% of total health expenditure was spent on routine immunization, and only slightly more when special campaigns were implemented [25]. India and Peru financed their EPI programs almost exclusively from internal government resources, while Vietnam and Uganda financed 25% and 50% of their programs, respectively, from external sources, such as the GAVI Alliance or other donors. The cost per fully immunized child ranged from just more than US$ 7 to US$ 21, depending on the presentation of the six core antigens2 and the inclusion of hepatitis B and Haemophilus influenzae B vaccines. Immunization budgets have increased significantly in three of the project countries, but only modestly for Vietnam (Table 3). We found differences in the allocation of program costs for immunization services between countries that were decentralized and those with more centralized implementation of their programs.
1 According to WHO National Health Accounts, the average health expenditure as a percentage of GDP is 4.1% for low-income countries and 11.2% among highincome countries (http://www.who.int/nha/country/Regional Averages by WB Income group-En.xls). 2 Hepatitis B vaccine had varying presentations across the countries. For example, it was given as a stand-alone vaccination to infants in India, but is one of the components of the pentavalent vaccine used in Uganda.
In decentralized systems, such as Vietnam, a larger proportion of program costs, especially those related to local personnel, transport, and maintenance of the cold chain were covered by local governments. In centrally sponsored immunization schemes, such as India, state governments contributed the majority of costs to the overall public health expenditure, which included paying vaccinator salaries as well as paying for cold chain and logistics costs. Decision-makers interviewed noted the challenges of co-financing obligations for supporting program costs, as well as vaccine copayments, if the HPV vaccines were introduced in the public sector. 3.4. Vaccine logistics and cold chain systems Structures and processes for vaccine delivery, transport, and storage were broadly similar across project countries, reflective of currently recommended EPI standards [26,27]. Except for India, where the vaccines were delivered by manufacturers directly to regional vaccine stores in each state, the project countries received the vaccines at national vaccine storage facilities. Vaccine distribution occurred from national stores to provincial or regional stores, then to district stores, with final distribution to health facilities occurring via cold boxes or vaccine carriers with preconditioned icepacks. Health facilities with refrigerators functioning at an appropriate temperature (+2 ◦ C to +8 ◦ C) and constant energy supplies sometimes operated as storage facilities. Vaccine distribution was implemented in accordance with the user rates and storage capacity. Respondents agreed that before introducing a new vaccine such as HPV, a systematic cold chain inventory was necessary to establish whether excess storage capacity existed to accommodate the additional volume. All the four project countries identified some excess cold chain capacity: India reported the greatest excess capacity at state level; Uganda reported the least excess capacity in national stores; and Peru noted no excess capacity and suggested the greatest need was at the local level. Uganda and Vietnam noted some refrigerators were out-ofservice and required repair. Shortages of liquid propane gas and cylinders were mentioned as a potential barrier to HPV vaccine introduction in Uganda. In Vietnam, many health facilities in mountainous regions lacked refrigerators; if existent, they were often domestic models that could not sustain an adequate storage temperature. This resulted in dependency on cold boxes, vaccine carriers, and frozen icepacks, which were in short supply. Lastly, human resources required specifically for cold chain and logistics management were reported to be limited in Gujarat state (India) and Vietnam, but not in Peru or Uganda. Additional staff to manage vaccine distribution may be needed if HPV vaccine were introduced. 3.5. Health information systems and human resources Each national EPI provided a client-retained vaccination card to record when vaccinations were administered to infants and pregnant women. Each program collected and analyzed vaccination coverage data. In all the four project countries, vaccination coverage data were collected through daily vaccination session tally sheets, consolidated upward through district and provincial/regional levels to the national level to generate coverage estimates. Computerization of data collection varied across countries, and was most often found at higher levels (e.g., national, regional, and district). Each project country also maintained a system for detecting, reporting, and investigating any reported or suspected serious adverse events following immunization (AEFI). Respondents noted government sensitivity to the negative publicity associated with reported AEFIs, regardless of causal association. Current mech-
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anisms for monitoring AEFIs and coverage were reported to be adequate should HPV vaccine be introduced into the national program. All countries stressed the need for additional training on HPV vaccines and cervical cancer, if HPV vaccine introduction occurred. Information on cervical cancer, its causes, risk factors, prevention, and HPV vaccine was lacking among many health professionals interviewed—who would be expected to be primary and secondary influencers for HPV vaccine efforts. 3.6. Effective delivery strategies for the HPV vaccines Respondents included in the health system component weighed the advantages and disadvantages of various delivery strategies for the HPV vaccines, bearing in mind their current systems, cold chain and storage capacities, and the target population of 10- to 14year-old girls. In all the four project countries, there was consensus that the EPI represents potentially the most effective mechanism for delivering the HPV vaccines, in view of its established national reputation, infrastructure, and well-trained human resources. Full integration of the HPV vaccines into routine vaccine service delivery through fixed health facilities and mobile teams serving outreach sites was generally not considered viable by health workers and technical staff at the district level in India, Peru, and Uganda. This was primarily because of concerns about the impact on the workload of health workers and the potential difficulty in getting mothers to bring girls of this age to the clinics. However, in Vietnam, where a longstanding, well-established, and well-attended system of vaccine delivery at fixed health centers was reported, respondents suggested the HPV vaccines could be integrated into the routine system. A campaign approach for HPV vaccine delivery was discussed initially, due to perceived synergies with age groups already targeted for JE, YF, or measles vaccination campaigns. However, when examined more closely, the three-dose HPV vaccine schedule and the single-dose annual campaign schedules were not compatible. A school-based strategy was identified by the majority of respondents in all the four project countries as being the most convenient and effective way of reaching 10- to 14-year-old girls, as the majority of girls in this age group were easily accessible at school. Initiatives, such as the Universal Primary Education policy in Uganda, have resulted in school enrollment increases [28], and were mentioned by respondents as justification for school-based delivery of the HPV vaccines. In India, vaccinating continuously in schools (every month) versus at fixed times according to the three-dose schedule for HPV was discussed. In Peru and Uganda, the advantages and disadvantages of vaccinating girls in school by age or by grade/class were considered. Vaccinating by age was seen as more challenging logistically, as some girls may not know their exact age. Despite the fairly wide age range in grades/classes in rural schools, arising from children starting school late and/or repeating grades, the logistic simplicity of vaccinating a single grade appealed to most health workers and technical staff at the district level. Generally, integration of HPV vaccination with adolescent health services or cervical cancer screening and treatment services was not considered a feasible approach. However, in Uganda, health policymakers and program managers strongly supported the idea of integrating HPV vaccine into CDP. This program was noted to be well-established, enjoyed a high level of community acceptance, and incorporated mechanisms for reaching out-ofschool girls. Funding earmarked from the national health budget and organized roles and responsibilities within communities were mentioned as facilitators to making this delivery approach effective. In India, linking HPV vaccination with existing TT vaccination or vitamin A distribution was suggested as a possible integrated
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delivery mechanism that could also be supplemented by health and hygiene education for girls. In this way, HPV vaccinations were considered a vehicle to strengthen other services as well as add new services for this population. 4. Discussion Our study of the health system and immunization financing structures in four developing countries sought to explore opportunities and challenges for future HPV vaccine introduction that may be particularly unique to these low-resource settings. The themes explored were similar to those considered most relevant for new vaccine introduction [11]. Using a mixed-method approach employing qualitative and quantitative techniques combined with literature and program document review, we hoped to elucidate the breadth of the concerns that may be broadly applicable to other developing countries. To this end, what are the implications of our results for effective HPV vaccine delivery strategies in these settings? Health services specifically targeted to younger adolescents, 10–14 years of age, are sparse, not routine, and if they do occur, are usually one-time interventions, such as distribution of vitamin A or antihelminthics or mass vaccination campaigns. The current immunization systems are robust and incorporate common elements for vaccine delivery recommended by WHO, such as age-appropriate vaccine schedules, health infrastructures and technical guidelines for human resources, vaccine logistics and cold chains, AEFI monitoring, and data collection and analysis, to achieve high levels of vaccination coverage [26,27]. Expenditures for these systems represent a very small fraction (<1%) of the total health expenditures in all the four countries. In each country, experience with providing health services in the school setting affords an opportunity for successful HPV vaccine delivery. Recent publications have suggested potential barriers or challenges to HPV vaccine delivery that are not borne out by the results of our study [7,9]. WHO has suggested that delivery of HPV vaccine to the 9- to 13-year-old age group will be particularly challenging because they are not normally included in country EPI programs, and school-based delivery schemes may be limited for this age group due to nonattendance or low attendance [7]. However, the respondents in our study noted that country EPI programs were best placed to deliver HPV vaccine given their expertise with the appropriate system support. Needs identified to strengthen the cold chain and health system infrastructure [9] included increasing refrigerator capacity at local levels (especially important if vaccine was supplied as single-dose vials and if other new vaccines will soon be introduced as well), replacing nonfunctioning equipment, ensuring adequate supply of fuel, and providing additional training to health workers. Brabin et al. [29] suggests the sexual nature of HPV infection would affect recommendation of HPV vaccine by health providers, and Paavonen and Lehtinen [30] argue that the gender-specific nature of a vaccine for a sexually transmitted infection may present difficulties. However, the sexual component of HPV transmission dynamics was rarely mentioned by our study respondents. This could reflect a bias in our data collection, as we contextualized HPV vaccine as cervical cancer prevention; however, as Bingham et al. [31] and Katahoire et al. [21] conclude, communication messages focusing on HPV vaccine as a preventive measure against cervical cancer may result in broader acceptability of the vaccine at all levels—parents, health workers, teachers, and policymakers. Challenges exist with a school-based delivery approach. The timing of the school year is fixed and the dosing schedule for HPV spans 6 months; thus, careful planning will be required to ensure all the three doses are delivered during one school year while accommodating vacation and examination schedules [32]. Typical
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vaccine delivery schedules use age as a selection basis for those eligible, but in schools, a grade-based delivery approach may be more efficient. Respondents from Uganda noted a wide age range for girls in some grades. Effective mechanisms for reaching outof-school girls will need to be considered for any school-based delivery program [7], as was mentioned by respondents from India. Despite these challenges, delivering the HPV vaccines at school may provide an opportunity to link other health interventions [9] (a sentiment expressed by many study respondents and a recommendation encouraged by WHO [7]), and also may provide a catalyst to encourage partnerships between health and education, reproductive health and immunization, and other key stakeholders [7]. Finally, any delivery program must be adequately supported financially, not just for the supply of vaccine, but also for the operational costs. The feasibility and sustainability of an HPV vaccination program will depend on the vaccine price and the supporting program costs to introduce HPV vaccine, within the context of overall health financing and specific immunization multiyear plans and projected budgets. We have seen in our results that in the past decade, there has been a trend of increasing immunization financing. This renewed interest in immunization program support from a financial perspective can be harnessed to advocate effectively with policymakers to consider full or partial co-funding to support HPV vaccine introduction [33]. While our summary provides practical information about health systems for HPV vaccine introduction in low-resource settings, there are some limitations to be noted. We synthesized data included in comprehensive technical reports from our formative research, rather than analyzing the original raw data from focus group discussions, in-depth interviews, vaccine session observations, immunization expert workshops, and exit interviews with mothers. Therefore, our study relied on culling major themes that were previously identified. Additionally, while our theme-based analysis approach was an inductive process recommended for qualitative data [24,34], we could not discern whether missing data were not collected or just not reported in the research report. Third, the countries included in this study were selected based on their representativeness of the region, burden of cervical cancer, health system infrastructure, and potential to adopt the HPV vaccines, but they may not be fully representative of all low-resource areas. Lastly, the study populations included in our research were purposively selected through a variety of techniques and were not systematically sampled for representativeness. 5. Conclusion Our findings suggest that low-resource settings may be able to successfully adopt the HPV vaccines, provided the health system structures and immunization financing options were well understood; the delivery strategy built off the existing strengths of national EPI programs with strong partnerships between other sectors, such as education, maternal–child health and reproductive health; system strengthening for effective vaccine delivery was supported; and schools could effectively be used as a venue in all the four countries. Overcoming institutional and implementation barriers will be key to program success. Demonstration projects to model routine delivery of HPV vaccine are being undertaken in all the four countries utilizing the findings from this research. Careful evaluation of those activities will reveal how well these qualitative findings predict actual practice. Acknowledgments Dr. Robin Biellik, lead author, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We wish to express our thanks
to the respective country governments, our colleagues, research partners, and study participants who contributed to the formative research studies in India, Peru, Uganda, and Vietnam. Special thanks to Dr. Vivien Tsu for her insightful comments to earlier drafts of this manuscript. Generous funding for this work was provided through a grant to PATH from the Bill & Melinda Gates Foundation.
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