Healthcare Costs and Life-years Gained From Treatments Within the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) Trial on Cryptococcal Meningitis: A Comparison of Antifungal Induction Strategies in Sub-Saharan Africa.

BACKGROUND: Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses. METHODS: Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done. RESULTS: Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91-1210) per life-year saved. CLINICAL TRIALS REGISTRATION: ISRCTN45035509. CONCLUSIONS: Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments.

Impact and cost-effectiveness of new tuberculosis vaccines in low- and middle-income countries.

To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40-80% efficacy, and to be targeted at "infants" or "adolescents/adults." Vaccine prices were tiered by income group (US $1.50-$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024-2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11-24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42-1.58) million TB cases could be prevented at $1,692 ($634-$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle-, and upper-middle-income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies.

Social mobilisation, consent and acceptability: a review of human papillomavirus vaccination procedures in low and middle-income countries.

BACKGROUND: Social mobilisation during new vaccine introductions encourages acceptance, uptake and adherence to multi-dose schedules. Effective communication is considered especially important for human papillomavirus (HPV) vaccine, which targets girls of an often-novel age group. This study synthesised experiences and lessons learnt around social mobilisation, consent, and acceptability during 55 HPV vaccine demonstration projects and 8 national programmes in 37 low and middle-income countries (LMICs) between January 2007 and January 2015. METHODS: A qualitative study design included: (i) a systematic review, in which 1,301 abstracts from five databases were screened and 41 publications included; (ii) soliciting 124 unpublished documents from governments and partner institutions; and (iii) conducting 27 key informant interviews. Data were extracted and analysed thematically. Additionally, first-dose coverage rates were categorised as above 90 %, 90-70 %, and below 70 %, and cross-tabulated with mobilisation timing, message content, materials and methods of delivery, and consent procedures. RESULTS: All but one delivery experience achieved over 70 % first-dose coverage; 60 % achieved over 90 %. Key informants emphasized the benefits of starting social mobilisation early and actively addressing rumours as they emerged. Interactive communication with parents appeared to achieve higher first-dose coverage than non-interactive messaging. Written parental consent (i.e., opt-in), though frequently used, resulted in lower reported coverage than implied consent (i.e., opt-out). Protection against cervical cancer was the primary reason for vaccine acceptability, whereas fear of adverse effects, exposure to rumours, lack of project/programme awareness, and schoolgirl absenteeism were major reasons for non-vaccination. CONCLUSIONS: Despite some challenges in obtaining parental consent and addressing rumours, experiences indicated effective social mobilisation and high HPV vaccine acceptability in LMICs. Social mobilisation, consent, and acceptability lessons were consistent across world regions and HPV vaccination projects/programmes. These can be used to guide HPV vaccination communication strategies without additional formative research.

The economic burden of pneumonia and meningitis among children less than five years old in Hanoi, Vietnam.

OBJECTIVE: To estimate the average treatment costs of pneumonia and meningitis among children under five years of age in a tertiary hospital in Hanoi, Vietnam from societal, health sector and household perspectives. METHODS: We used a cost-of-illness approach to identify cost categories to be included for different perspectives. A prospective survey was conducted among eligible patients to get detailed personal costing items. RESULTS: From the perspective of the health sector, the mean costs for treating a case of pneumonia and meningitis were USD 180 and USD 300, respectively. From the household's perspective, the average treatment costs were USD 272 for pneumonia and USD 534 for meningitis. When also including indirect costs, the average total treatment costs from the societal perspective were USD 318 for pneumonia and USD 727 for meningitis. CONCLUSION: The study contributed to limited evidence on the high treatment costs of pneumonia and meningitis to the Vietnamese society, which is useful for a cost-effectiveness analysis of Haemophilus influenzae type b vaccine or other relevant disease preventions. It also indicated a need to re-evaluate the health insurance policy for children under 6 years old, so that the unnecessarily high out-of-pocket costs of these diseases are reduced.

Cost-effectiveness of eye care services in Zambia.

OBJECTIVE: To estimate the cost-effectiveness of cataract surgery and refractive error/presbyopia correction in Zambia. METHODS: Primary data on costs and health related quality of life were collected in a prospective cohort study of 170 cataract and 113 refractive error/presbyopia patients recruited from three health facilities. Six months later, follow-up data were available from 77 and 41 patients who had received cataract surgery and spectacles, respectively. Costs were determined from patient interviews and micro-costing at the three health facilities. Utility values were gathered by administering the EQ-5D quality of life instrument immediately before and six months after cataract surgery or acquiring spectacles. A probabilistic state-transition model was used to generate cost-effectiveness estimates with uncertainty ranges. RESULTS: Utility values significantly improved across the patient sample after cataract surgery and acquiring spectacles. Incremental costs per Quality Adjusted Life Years gained were US$ 259 for cataract surgery and US$ 375 for refractive error correction. The probabilities of the incremental cost-effectiveness ratios being below the Zambian gross national income per capita were 95% for both cataract surgery and refractive error correction. CONCLUSION: In spite of proven cost-effectiveness, severe health system constraints are likely to hamper scaling up of the interventions.

Measuring the health systems impact of disease control programmes: a critical reflection on the WHO building blocks framework.

BACKGROUND: The WHO health systems Building Blocks framework has become ubiquitous in health systems research. However, it was not developed as a research instrument, but rather to facilitate investments of resources in health systems. In this paper, we reflect on the advantages and limitations of using the framework in applied research, as experienced in three empirical vaccine studies we have undertaken. DISCUSSION: We argue that while the Building Blocks framework is valuable because of its simplicity and ability to provide a common language for researchers, it is not suitable for analysing dynamic, complex and inter-linked systems impacts. In our three studies, we found that the mechanical segmentation of effects by the WHO building blocks, without recognition of their interactions, hindered the understanding of impacts on systems as a whole. Other important limitations were the artificial equal weight given to each building block and the challenge in capturing longer term effects and opportunity costs. Another criticism is not of the framework per se, but rather how it is typically used, with a focus on the six building blocks to the neglect of the dynamic process and outcome aspects of health systems.We believe the framework would be improved by making three amendments: integrating the missing "demand" component; incorporating an overarching, holistic health systems viewpoint and including scope for interactions between components. If researchers choose to use the Building Blocks framework, we recommend that it be adapted to the specific study question and context, with formative research and piloting conducted in order to inform this adaptation. SUMMARY: As with frameworks in general, the WHO Building Blocks framework is valuable because it creates a common language and shared understanding. However, for applied research, it falls short of what is needed to holistically evaluate the impact of specific interventions on health systems. We propose that if researchers use the framework, it should be adapted and made context-specific.

Effect of increasing active travel in urban England and Wales on costs to the National Health Service.

Increased walking and cycling in urban areas and reduced use of private cars could have positive effects on many health outcomes. We estimated the potential effect of increased walking and cycling in urban England and Wales on costs to the National Health Service (NHS) for seven diseases--namely, type 2 diabetes, dementia, cerebrovascular disease, breast cancer, colorectal cancer, depression, and ischaemic heart disease--that are associated with physical inactivity. Within 20 years, reductions in the prevalences of type 2 diabetes, dementia, ischaemic heart disease, cerebrovascular disease, and cancer because of increased physical activity would lead to savings of roughly UK£17 billion (in 2010 prices) for the NHS, after adjustment for an increased risk of road traffic injuries. Further costs would be averted after 20 years. Sensitivity analyses show that results are invariably positive but sensitive to assumptions about time lag between the increase in active travel and changes in health outcomes. Increasing the amount of walking and cycling in urban settings could reduce costs to the NHS, permitting decreased government expenditure on health or releasing resources to fund additional health care.

Impact and cost-effectiveness of Haemophilus influenzae type b conjugate vaccination in India.

OBJECTIVE: To estimate the potential health impact and cost-effectiveness of nationwide Haemophilus influenzae type b (Hib) vaccination in India. STUDY DESIGN: A decision support model was used, bringing together estimates of demography, epidemiology, Hib vaccine effectiveness, Hib vaccine costs, and health care costs. Scenarios favorable and unfavorable to the vaccine were evaluated. State-level analyses indicate where the vaccine might have the greatest impact and value. RESULTS: Between 2012 and 2031, Hib conjugate vaccination is estimated to prevent over 200 000 child deaths (∼1% of deaths in children <5 years of age) in India at an incremental cost of US$127 million per year. From a government perspective, state-level cost-effectiveness ranged from US$192 to US$1033 per discounted disability adjusted life years averted. With the inclusion of household health care costs, cost-effectiveness ranged from US$155-US$939 per discounted disability adjusted life year averted. These values are below the World Health Organization thresholds for cost effectiveness of public health interventions. CONCLUSIONS: Hib conjugate vaccination is a cost-effective intervention in all States of India. This conclusion does not alter with plausible changes in key parameters. Although investment in Hib conjugate vaccination would significantly increase the cost of the Universal Immunization Program, about 15% of the incremental cost would be offset by health care cost savings. Efforts should be made to expedite the nationwide introduction of Hib conjugate vaccination in India.

How can measles eradication strengthen health care systems?

Elimination and eradication initiatives are generally delivered through a vertical approach, which can potentially hamper health systems. We propose 3 approaches by which a measles eradication initiative can ensure that health systems are left strengthened when the eradication goal has been accomplished. First, focus should be placed on strengthening routine vaccination, which could generate positive trickle-up effects on other primary health care services. Second, increased integration with multifunctional health services should be emphasized. Third, efforts should be made to change traditional donor behavior that prioritizes vaccination campaigns and uses uncoordinated staff incentives.

Cost-effectiveness of a Community-based Hypertension Improvement Project (ComHIP) in Ghana: results from a modelling study.

OBJECTIVE: To undertake a cost-effectiveness analysis of a Community-based Hypertension Improvement Project (ComHIP) compared with standard hypertension care in Ghana. DESIGN: Cost-effectiveness analysis using a Markov model. SETTING: Lower Manya Krobo, Eastern Region, Ghana. INTERVENTION: We evaluated ComHIP, an intervention with multiple components, including: community-based education on cardiovascular disease (CVD) risk factors and healthy lifestyles; community-based screening and monitoring of blood pressure by licensed chemical sellers and CVD nurses; community-based diagnosis, treatment, counselling, follow-up and referral of hypertension patients by CVD nurses; telemedicine consultation by CVD nurses and referral of patients with severe hypertension and/or organ damage to a physician; information and communication technologies messages for healthy lifestyles, treatment adherence support and treatment refill reminders for hypertension patients; Commcare, a cloud-based health records system linked to short-message service (SMS)/voice messaging for treatment adherence, reminders and health messaging. ComHIP was evaluated under two scale-up scenarios: (1) ComHIP as currently implemented with support from international partners and (2) ComHIP under full local implementation. MAIN OUTCOME MEASURES: Incremental cost per disability-adjusted life-year (DALY) averted from a societal perspective over a time horizon of 10 years. RESULTS: ComHIP is unlikely to be a cost-effective intervention, with current ComHIP implementation and ComHIP under full local implementation costing on average US$12 189 and US$6530 per DALY averted, respectively. Results were robust to uncertainty analyses around model parameters. CONCLUSIONS: High overhead costs and high patient costs in ComHIP suggest that the societal costs of ensuring appropriate hypertension care are high and may not produce sufficient impact to achieve cost-effective implementation. However, these results are limited by the evidence quality of the effectiveness estimates, which comes from observational data rather than from randomised controlled study design.

Budget line items for immunization in 33 African countries.

When seeking to ensure financial sustainability of a health programme, existence of a line item in the Ministry of Health (MOH) budget is often seen as an essential, first step. We used immunization as a reference point for cross-country comparison of budgeting methods in Sub-Saharan African countries. Study objectives were to (1) verify the number and types of budget line items for immunization services, (2) compare budget execution with budgeted amounts and (3) compare values with annual immunization expenditures reported to WHO and UNICEF. MOH budgets for 2016 and/or 2017 were obtained from 33 countries. Despite repeated attempts, budgets could not be retrieved from five countries (Chad, Eritrea, Guinea Bissau, Somalia and South Sudan), and we were only able to gather budget execution from eight countries. The number of immunization line items ranged between 0 and 42, with a median of eight. Immunization donor funding was included in 10 budgets. Differences between budgeted amounts and expenditures reported to WHO and UNICEF were greater than 50% in 66% of countries. Immunization budgets per child in the birth cohort ranged from US$1.37 (Democratic Republic of Congo) to US$67.51 (Central African Republic), with an average of US$10.05. Out of the total Government health budget, immunization comprised between 0.04% (Madagascar) and 5.67% (Benin), with an average of 1.98% across the countries, when excluding on-budget donor funds. It was challenging to obtain MOH budgets in many countries and it was largely impossible to access budget execution reports, preventing us from assessing budget credibility. Large differences between budgets and expenditures reported to WHO and UNICEF are likely due to inconsistent interpretations of reporting requirements, diverse approaches to reporting donor funds, challenges in extracting the relevant information from public financial management systems and broader issues of public financial management capacity in MOH staff.

Cost-effectiveness analysis of rapid diagnostic test, microscopy and syndromic approach in the diagnosis of malaria in Nigeria: implications for scaling-up deployment of ACT.

BACKGROUND: The diagnosis and treatment of malaria is often based on syndromic presentation (presumptive treatment) and microscopic examination of blood films. Treatment based on syndromic approach has been found to be costly, and contributes to the development of drug resistance, while microscopic diagnosis of malaria is time-consuming and labour-intensive. Also, there is lack of trained microscopists and reliable equipment especially in rural areas of Nigeria. However, although rapid diagnostic tests (RDTs) have improved the ease of appropriate diagnosis of malaria diagnosis, the cost-effectiveness of RDTs in case management of malaria has not been evaluated in Nigeria. The study hence compares the cost-effectiveness of RDT versus syndromic diagnosis and microscopy. METHODS: A total of 638 patients with fever, clinically diagnosed as malaria (presumptive malaria) by health workers, were selected for examination with both RDT and microscopy. Patients positive on RDT received artemisinin-based combination therapy (ACT) and febrile patients negative on RDT received an antibiotic treatment. Using a decision tree model for a hypothetical cohort of 100,000 patients, the diagnostic alternatives considered were presumptive treatment (base strategy), RDT and microscopy. Costs were based on a consumer and provider perspective while the outcome measure was deaths averted. Information on costs and malaria epidemiology were locally generated, and along with available data on effectiveness of diagnostic tests, adherence level to drugs for treatment, and drug efficacy levels, cost-effectiveness estimates were computed using TreeAge programme. Results were reported based on costs and effects per strategy, and incremental cost-effectiveness ratios. RESULTS: The cost-effectiveness analysis at 43.1% prevalence level showed an incremental cost effectiveness ratio (ICER) of 221 per deaths averted between RDT and presumptive treatment, while microscopy is dominated at that level. There was also a lesser cost of RDT ($0.34 million) compared to presumptive treatment ($0.37 million) and microscopy ($0.39 million), with effectiveness values of 99,862, 99,735 and 99,851 for RDT, presumptive treatment and microscopy, respectively. Cost-effectiveness was affected by malaria prevalence level, ACT adherence level, cost of ACT, proportion of non-malaria febrile illness cases that were bacterial, and microscopy and RDT sensitivity. CONCLUSION: RDT is cost-effective when compared to other diagnostic strategies for malaria treatment at malaria prevalence of 43.1% and, therefore, a very good strategy for diagnosis of malaria in Nigeria. There is opportunity for cost savings if rapid diagnostic tests are introduced in health facilities in Nigeria for case management of malaria.

The economic burden of inpatient paediatric care in Kenya: household and provider costs for treatment of pneumonia, malaria and meningitis.

BACKGROUND: Knowledge of treatment cost is essential in assessing cost effectiveness in healthcare. Evidence of the potential impact of implementing available interventions against childhood illnesses in developing countries challenges us to define the costs of treating these diseases. The purpose of this study is to describe the total costs associated with treatment of pneumonia, malaria and meningitis in children less than five years in seven Kenyan hospitals. METHODS: Patient resource use data were obtained from largely prospective evaluation of medical records and household expenditure during illness was collected from interviews with caretakers. The estimates for costs per bed day were based on published data. A sensitivity analysis was conducted using WHO-CHOICE values for costs per bed day. RESULTS: Treatment costs for 572 children (pneumonia = 205, malaria = 211, meningitis = 102 and mixed diagnoses = 54) and household expenditure for 390 households were analysed. From the provider perspective the mean cost per admission at the national hospital was US $95.58 for malaria, US $177.14 for pneumonia and US $284.64 for meningitis. In the public regional or district hospitals the mean cost per child treated ranged from US $47.19 to US $81.84 for malaria and US $54.06 to US $99.26 for pneumonia. The corresponding treatment costs in the mission hospitals were between US $43.23 to US $88.18 for malaria and US $ 43.36 to US $142.22 for pneumonia. Meningitis was treated for US $ 189.41 at the regional hospital and US $ 201.59 at one mission hospital. The total treatment cost estimates were sensitive to changes in the source of bed day costs. The median treatment related household payments within quintiles defined by total household expenditure differed by type of facility visited. Public hospitals recovered up to 40% of provider costs through user charges while mission facilities recovered 44% to 100% of costs. CONCLUSION: Treatments cost for inpatient malaria, pneumonia and meningitis vary by facility type, with mission and tertiary referral facilities being more expensive compared to primary referral. Households of sick children contribute significantly towards provider cost through payment of user fees. These findings could be used in cost effectiveness analysis of health interventions.

Cost analysis of integrated community case management of childhood malaria, diarrhea and pneumonia enhanced by mobile health technology in rural Zambia.

Integrated community case management (iCCM) of malaria, diarrhea, and pneumonia is a comprehensive, equitybased strategy to improve treatment access for underserved children under five years old. This paper presents data on cost of iCCM and incremental costs of mHealth enhanced supervision and supply chain management in Zambia. We collected cost data using three questionnaires applied at national, district, health facility and community levels. We interviewed 40 health facility supervisors and 75 community health workers. A provider perspective and an ingredient costing method was used. We entered and analyzed data in a customized excel costing tool. The result shows that total iCCM cost per patient contact was USD 18.43. The incremental cost of using the mHealth intervention per child contact for all iCCM conditions was USD 11.35. The incremental cost per treatment of diarrhea, pneumonia, and malaria with mHealth intervention was USD 9.58, USD 10.37 and USD 12.82. Program costs accounted for 67% of the total, and the largest share was associated with supervision estimated at 36%, followed by supply chain management at 27%. This study has provided valuable information to policy makers on how much it costs to implement iCCM program using mHealth interventions.

Household costs of seeking BCG vaccination in rural Guinea-Bissau.

In Guinea-Bissau, a vial of BCG vaccine is often not opened unless 10 infants are present for vaccination, with the aim of reducing vaccine wastage. This causes delays in vaccination, as previously demonstrated in Guinea-Bissau and other low-income countries. Reducing wastage of BCG vaccine to save money may deprive infants of important health benefits and transfer costs from the vaccination programme to mothers. Using the Bandim Health Project's rural Health and Demographic Surveillance System, we interviewed mothers of infants aged 1-11 months about household costs of seeking BCG vaccination. On average mothers took their infant for BCG vaccination 1.26 times before obtaining the vaccine. For mothers who had sought BCG vaccine for their infants the average cost was 1.89 USD for each BCG-vaccinated infant. Among BCG-unvaccinated infants at the time of interview, 42% had brought their infant for BCG vaccination in vain at an average cost of 2.83 USD.

Vaccine-preventable haemophilus influenza type B disease burden and cost-effectiveness of infant vaccination in Indonesia.

BACKGROUND: Most of Asia, including Indonesia, does not use Haemophilus influenzae type b (Hib) conjugate vaccines. We estimated total vaccine-preventable disease burden and the cost-effectiveness of Hib conjugate vaccine in Indonesia. METHODS: Hib pneumonia and meningitis incidences for children with access to health care were derived from a randomized vaccine probe study on Lombok Island, Indonesia during 1998-2002. Incidences were adjusted for limited access to care. Health system and patient out-of-pocket treatment cost data were collected concurrent with the probe study. For Hib vaccine in monovalent and combined (with DTP-HepB) presentations, we used 2007 UNICEF vaccine prices of US$3.30 and $3.75 per dose. RESULTS: For the 2007 Indonesian birth cohort, Hib vaccine would prevent meningitis in 1 of every 179 children, pneumonia in 1 of every 18 children, and 4.9% of mortality among those younger than 5 years. The total incremental societal costs of introducing Hib vaccine in monovalent and pentavalent presentations were, respectively, US$11.74 and $8.93 per child vaccinated. Annual discounted treatment costs averted amounted to 20% of pentavalent vaccine costs. For the pentavalent vaccine, the incremental costs per discounted death and disability adjusted life-year averted amounted to US$3102 and $74, respectively, versus $4438 and $102 for monovalent vaccine. CONCLUSIONS: Routine infant Hib vaccination would prevent a large burden of pediatric illness and death in Indonesia. Even without external funding support, Hib vaccine will be a highly cost-effective intervention in either a monovalent or pentavalent presentation based on commonly used benchmarks.

A bibliometric analysis of systematic reviews on vaccines and immunisation.

INTRODUCTION: SYSVAC is an online bibliographic database of systematic reviews and systematic review protocols on vaccines and immunisation compiled by the London School of Hygiene & Tropical Medicine and hosted by the World Health Organization (WHO) through their National Immunization Technical Advisory Groups (NITAG) resource centre (www.nitag-resource.org). Here the development of the database and a bibliometric review of its content is presented, describing trends in the publication of policy-relevant systematic reviews on vaccines and immunisation from 2008 to 2016. MATERIALS AND METHODS: Searches were conducted in seven scientific databases according to a standardized search protocol, initially in 2014 with the most recent update in January 2017. Abstracts and titles were screened according to specific inclusion criteria. All included publications were coded into relevant categories based on a standardized protocol and subsequently analysed to look at trends in time, topic, area of focus, population and geographic location. RESULTS: After screening for inclusion criteria, 1285 systematic reviews were included in the database. While in 2008 there were only 34 systematic reviews on a vaccine-related topic, this increased to 322 in 2016. The most frequent pathogens/diseases studied were influenza, human papillomavirus and pneumococcus. There were several areas of duplication and overlap. DISCUSSION: As more systematic reviews are published it becomes increasingly time-consuming for decision-makers to identify relevant information among the ever-increasing volume available. The risk of duplication also increases, particularly given the current lack of coordination of systematic reviews on vaccine-related questions, both in terms of their commissioning and their execution. The SYSVAC database offers an accessible catalogue of vaccine-relevant systematic reviews with, where possible access or a link to the full-text. CONCLUSIONS: SYSVAC provides a freely searchable platform to identify existing vaccine-policy-relevant systematic reviews. Systematic reviews will need to be assessed adequately for each specific question and quality.

Experiences of operational costs of HPV vaccine delivery strategies in Gavi-supported demonstration projects.

From 2012 to 2016, Gavi, the Vaccine Alliance, provided support for countries to conduct small-scale demonstration projects for the introduction of the human papillomavirus vaccine, with the aim of determining which human papillomavirus vaccine delivery strategies might be effective and sustainable upon national scale-up. This study reports on the operational costs and cost determinants of different vaccination delivery strategies within these projects across twelve countries using a standardized micro-costing tool. The World Health Organization Cervical Cancer Prevention and Control Costing Tool was used to collect costing data, which were then aggregated and analyzed to assess the costs and cost determinants of vaccination. Across the one-year demonstration projects, the average economic and financial costs per dose amounted to US$19.98 (standard deviation ±12.5) and US$8.74 (standard deviation ±5.8), respectively. The greatest activities representing the greatest share of financial costs were social mobilization at approximately 30% (range, 6-67%) and service delivery at about 25% (range, 3-46%). Districts implemented varying combinations of school-based, facility-based, or outreach delivery strategies and experienced wide variation in vaccine coverage, drop-out rates, and service delivery costs, including transportation costs and per diems. Size of target population, number of students per school, and average length of time to reach an outreach post influenced cost per dose. Although the operational costs from demonstration projects are much higher than those of other routine vaccine immunization programs, findings from our analysis suggest that HPV vaccination operational costs will decrease substantially for national introduction. Vaccination costs may be decreased further by annual vaccination, high initial investment in social mobilization, or introducing/strengthening school health programs. Our analysis shows that drivers of cost are dependent on country and district characteristics. We therefore recommend that countries carry out detailed planning at the national and district levels to define a sustainable strategy for national HPV vaccine roll-out, in order to achieve the optimal balance between coverage and cost.

Lessons learnt from human papillomavirus (HPV) vaccination in 45 low- and middle-income countries.

OBJECTIVE: To synthesise lessons learnt and determinants of success from human papillomavirus (HPV) vaccine demonstration projects and national programmes in low- and middle-income countries (LAMICs). METHODS: Interviews were conducted with 56 key informants. A systematic literature review identified 2936 abstracts from five databases; after screening 61 full texts were included. Unpublished literature, including evaluation reports, was solicited from country representatives; 188 documents were received. A data extraction tool and interview topic guide outlining key areas of inquiry were informed by World Health Organization guidelines for new vaccine introduction. Results were synthesised thematically. RESULTS: Data were analysed from 12 national programmes and 66 demonstration projects in 46 countries. Among demonstration projects, 30 were supported by the GARDASIL® Access Program, 20 by Gavi, four by PATH and 12 by other means. School-based vaccine delivery supplemented with health facility-based delivery for out-of-school girls attained high coverage. There were limited data on facility-only strategies and little evaluation of strategies to reach out-of-school girls. Early engagement of teachers as partners in social mobilisation, consent, vaccination day coordination, follow-up of non-completers and adverse events was considered invaluable. Micro-planning using school/ facility registers most effectively enumerated target populations; other estimates proved inaccurate, leading to vaccine under- or over-estimation. Refresher training on adverse events and safe injection procedures was usually necessary. CONCLUSION: Considerable experience in HPV vaccine delivery in LAMICs is available. Lessons are generally consistent across countries and dissemination of these could improve HPV vaccine introduction.