The cost of human papillomavirus vaccination delivery at the administrative and health facility levels in the Philippines.

Background: The World Health Organization has recommended the inclusion of human papillomavirus (HPV) vaccines in national immunization programs to address the global problem of cervical cancer. In the Philippines, HPV vaccination was introduced in a phased approach in 2015. This study seeks to estimate the cost of delivery of the HPV vaccination program and its operational context in the Philippines. Methods: This was a retrospective, cross-sectional micro-costing study focused on ongoing HPV vaccination delivery and its operational context across all levels of the health system. Using structured questionnaires and data collection from secondary sources, the weighted mean financial and economic costs and costs per dose at the national, subnational, and health facility levels were estimated. Results: The weighted mean financial and economic costs per dose of the HPV vaccination program aggregated across all levels of the health system were $US3.72and $29.74, respectively. Activities contributing most significantly to costs were service delivery and vaccine collection or distribution and storage at the health facility and administrative levels, respectively. The opportunity costs for health worker and non-health worker time accounted for 77% of the economic cost per dose. Conclusion: The total weighted mean financial and economic costs of HPV delivery are within range of those reported in other countries. Costing studies can help identify cost drivers with local operational context to help inform policymakers and program managers in budgeting and planning interventions to improve program implementation.

The cost-effectiveness of human papillomavirus vaccination in the Philippines.

Cervical cancer is the second most common cancer among women in the Philippines. Human papillomavirus (HPV) vaccination provides protection from the most common cancer-causing HPV types. This analysis used a proportionate outcomes model to estimate the potential cost-effectiveness of four different HPV vaccine products-Cervarix™, Cecolin®, GARDASIL®, and GARDASIL®9-for routine HPV vaccination of 10 cohorts of 9-year-old girls from the government and societal perspectives. Model parameters included cervical cancer burden, healthcare and program costs, vaccine efficacy with and without potential cross-protection, and vaccination coverage. Univariate and probabilistic sensitivity analyses evaluated the impact of uncertainty on model results. Compared to no vaccination, HPV programs with Cecolin®, Cervarix™, and GARDASIL® are projected to be cost-effective at US$1,210, US$1,300, and US$2,043 per DALY averted, respectively, from the government perspective, and at US$173, US$263, and US$1,006 per DALY averted, respectively, from the societal perspective when cross-protection was considered. When direct comparisons were made across vaccines, GARDASIL® was dominated by Cervarix™ and Cecolin®. In a scenario where cross-protection was not considered, results were similar except that Cervarix™ and GARDASIL® were both dominated by Cecolin®. GARDASIL®9 was not cost-effective under any of the modeled scenarios.

Cost-effectiveness of rotavirus vaccination in the Philippines: A modeling study.

INTRODUCTION: Rotavirus gastroenteritis (RVGE) remains a leading cause of hospitalization and death in children under five years of age in the Philippines. Rotavirus (RV) vaccination was introduced into the national immunization program (NIP) in 2012 but has since been limited to one region due to cost considerations and conflicting local cost-effectiveness estimates. Updated estimates of the cost-effectiveness of RV vaccination are required to inform prioritization of national immunization activities. METHODS: We calculated the potential costs and benefits of rotavirus vaccination over a 10-year-period (2021-2031) from a government and societal perspective, comparing four alternative rotavirus vaccines: Rotavac, Rotasiil, Rotarix and Rotateq. For each vaccine, a proportionate outcomes model was used to calculate the expected number of disease events, DALYs, vaccination program costs, and healthcare costs, with and without vaccination. The primary outcome measure was the cost per DALY averted. Assuming each product would generate similar benefits, the dominant (lowest cost) product was identified. We then calculated the cost-effectiveness (US$ per Disability Adjusted Life Year [DALY] averted) of the least costly product and compared it to willingness-to-pay thresholds of 0.5 and 1 times the national GDP per capita ($3,485), and ran deterministic and probabilistic sensitivity analyses. RESULTS: Introducing any of the four rotavirus vaccines would avert around 40% of RVGE visits, hospitalizations, and deaths over the period 2021-2031. Over the same ten-year period, the incremental cost of vaccination from a government perspective was estimated to be around $104, $105, $220, and $277 million for Rotavac, Rotasiil, Rotarix and Rotateq, respectively. The equivalent cost from a societal perspective was $58, $60, $178 and $231 million. The cost-effectiveness of the least costly product (Rotavac) was $1,148 ($830-$1682) from a government perspective and $646 ($233-1277) from a societal perspective. All other products offered similar benefits but at a higher cost. There is a >99% probability that Rotavac would be cost-effective at a willingness-to-pay threshold set at 0.5 times the national GDP per capita. CONCLUSION: Both Rotavac and Rotasiil are likely to be cost-effective options in the Philippines, but it is not possible to say definitively which product should be preferred. Rotarix and Rotateq are expected to offer similar benefits at more cost, so would need to be priced far more competitively to be considered for introduction.

Timeliness of childhood vaccinations in the Philippines.

Timeliness of vaccinations is rarely part of monitoring in a routine immunization program. We reviewed infant immunization and conducted caregiver interviews in three regions in the Philippines from January to October 2016. We randomly selected thirty public health centers, one for each region. We defined timeliness of the receipt of antigen as within 4 weeks after the recommended age at vaccination. We assessed a total of 986 infants for timeliness of vaccination. The median age of receipt of vaccine was at 2.7 weeks (BCG), 10.1 weeks (Penta 1), and 21.7 weeks (Penta 3) compared to the recommended 0, 6, and 14 weeks of age, respectively. We found timely receipt only in 74.4% for BCG, 70.3% for Penta 1, and 39.1% for Penta 3 recipients. Thus, alongside declining immunization coverage, the infants in the Philippines had substantial delays in vaccine receipt.

Epidemiology of Japanese encephalitis in the Philippines prior to routine immunization.

BACKGROUND: Findings were published in 2015 that highlighted the endemicity of Japanese Encephalitis (JE) in the Philippines. The policymakers responded by conducting an immunization campaign and strengthening the surveillance system. Using data on the revitalized surveillance system, the epidemiology of JE in the country was updated. METHODS: Electronic databases were searched, and conference proceedings related to JE in the Philippines were identified until 31 December 2018. Surveillance data from 01 January 2014 to 31 December 2017 were used. The 2015 population census was used to estimate the national and regional incidence for children aged <15 years. RESULTS: Four studies reported the seroprevalence of JE in the Philippines, which showed increasing seroprevalence with increasing age. Seroprevalence rates were from 0% for infants (aged <1 year) to 65.7% in adolescents (12-18 years) before the immunization campaign. Among five studies on the clinical profile of JE, case fatality ranged from 0 to 21.1% and neurologic sequelae ranged from 5.2 to 81.8% of diagnosed cases. In the surveillance data, JE cases peaked annually from July to October, coinciding with the wet season. The national incidence was estimated at a minimum of 0.7 JE cases/100,000 among children aged <15 years, but higher rates were seen in the northern regions of the country. CONCLUSION: Improved surveillance affirmed the burden of JE in the Philippines. A subnational immunization campaign in April 2019 was conducted in the northern regions of the country. This paper highlights the importance of including the JE vaccine in the immunization program and sustained high-quality surveillance to monitor its impact on JE control.

Trends in dengue research in the Philippines: A systematic review.

Dengue is an important public health problem in the Philippines. We sought to describe the trends in dengue research in the country. We searched four databases and identified published studies on dengue research in the Philippines during the past 60 years. We reviewed 135 eligible studies, of which 33% were descriptive epidemiologic studies or case series, 16% were entomologic or vector control studies, 12% were studies on dengue virology and serologic response, 10% were socio-behavioral and economics studies, 8% were clinical trials, 7% were on burden of disease, 7% were investigations on markers of disease severity, 5% were on dengue diagnostics, and 2% were modeling studies. During the last decade, dengue research in the Philippines has increased and evolved from simple descriptive studies to those with more complex and diverse designs. We identified several key topics where more research would be useful.

Urine Xpert MTB/RIF for the diagnosis of childhood tuberculosis.

INTRODUCTION: Xpert MTB/RIF is recommended for the simultaneous detection of tuberculosis (TB) and rifampicin resistance directly from sputum specimens. Since young children cannot always expectorate, we assessed urine as a possible specimen source to diagnose TB in children using Xpert MTB/RIF. METHODS: During a field study to enhance childhood TB identification, spot urine samples were prospectively collected from consecutive ambulatory children aged 0 to 14 years presenting with presumptive pulmonary TB in community health centers. Urine Xpert MTB/RIF was performed by blinded technicians in 182 samples using 2ml of unprocessed urine. RESULTS: The mean age of presumptive TB cases was 5.9 years (median 5.4, range 0.1 to 14.7) with more males (113, 62%) compared to females. All urine samples tested negative for Xpert MTB/RIF, regardless of whether concentration was performed or not. Out of these 182 presumptive TB cases, 50 (28%) were clinically diagnosed and 5 (3%) were bacteriologically diagnosed to have TB disease using either sputum or nasopharyngeal aspirate specimens. CONCLUSIONS: In this community-based study, urine Xpert MTB/RIF does not appear to contribute to the diagnosis of childhood TB.

Introduction of inactivated poliovirus vaccine in the Philippines: Effect on health care provider and infant caregiver attitudes and practices.

BACKGROUND: The introduction of inactivated poliovirus vaccine (IPV) to the Philippines' national immunization schedule meant the addition of a third injectable vaccine at a child's 14-week immunization visit. Although previous studies have shown that providing multiple vaccines at the same time affected neither the risk of severe adverse events nor vaccine efficacy, concerns were raised that providing three injections at a single visit, with two injections in one leg, might be unacceptable to health care providers (HCP) and infant caregivers. METHODS: We conducted pre- and post-IPV introduction surveys on the acceptance and acceptability of the additional injectable vaccine in three of the Philippines' 17 administrative regions. Regions 3 and 6 were included in the pre-introduction phase and Regions 3, 6 and 10 were included in the post-introduction phase. Thirty public health centers (PHCs) were randomly sampled from each region. HCPs and infant caregivers were interviewed. In addition, vaccination records from a minimum of 20 eligible children pre-introduction and 10 children post-introduction per PHC were reviewed. RESULTS AND DISCUSSION: We interviewed 89 HCPs and 286 infant caregivers during the pre-introduction phase and 137 HCPs and 455 caregivers during the post-introduction phase. Among 986 vaccination records reviewed post-introduction, 84% (n = 826) of children received all three recommended injections at one visit, with a range from 61% (209/342) in Region 10 to 100% (328/328) in Region 3. The proportion of HCPs reporting that they had administered three or more injectable vaccines and the proportion of caregivers that would be comfortable with their child receiving three or more injectable vaccines at one visit increased from pre- to post-introduction (p < 0.0001 for both). Eighty-seven percent of HCPs that had administered three or more injectable vaccines post-introduction reported being comfortable or very comfortable with the number of vaccines they had administered.

The burden of congenital rubella syndrome in the Philippines: results from a retrospective assessment.

INTRODUCTION: In line with the regional aim of eliminating rubella and congenital rubella syndrome (CRS), phased introduction of rubella-containing vaccines (RCV) in the Philippines' routine immunization programme began in 2010. We estimated the burden of CRS in the country before widespread nationwide programmatic RCV use. METHODS: We performed a retrospective chart review in four tertiary hospitals. Children born between 1 January 2009 and 31 December 2014 and identified as possible CRS cases based on the presence of one or more potential manifestations of CRS documented in hospital or clinic charts were reviewed. Cases that met the clinical case definition of CRS were classified as either confirmed (with laboratory confirmation) or probable (without laboratory confirmation). Cases that did not fulfil the criteria for either confirmed or probable CRS were excluded from the analysis. RESULTS: We identified 18 confirmed and 201 probable cases in this review. Depending on the hospital, the estimated incidence of CRS ranged from 30 to 233 cases per 100 000 live births. The estimated national burden of CRS was 20 to 31 cases per 100 000 annually. DISCUSSION: This is the first attempt to assess the national CRS burden using in-country hospital data in the Philippines. Prospective surveillance for CRS and further strengthening of the ongoing measles-rubella surveillance are necessary to establish accurate estimates of the burden of CRS and the impact of programmatic RCV use in the future.

Epidemiology of Japanese encephalitis in the Philippines: a systematic review.

BACKGROUND: Japanese encephalitis virus (JEV) is an important cause of encephalitis in most of Asia, with high case fatality rates and often significant neurologic sequelae among survivors. The epidemiology of JE in the Philippines is not well defined. To support consideration of JE vaccine for introduction into the national schedule in the Philippines, we conducted a systematic literature review and summarized JE surveillance data from 2011 to 2014. METHODS: We conducted searches on Japanese encephalitis and the Philippines in four databases and one library. Data from acute encephalitis syndrome (AES) and JE surveillance and from the national reference laboratory from January 2011 to March 2014 were tabulated and mapped. RESULTS: We identified 29 published reports and presentations on JE in the Philippines, including 5 serologic surveys, 18 reports of clinical cases, and 8 animal studies (including two with both clinical cases and animal data). The 18 clinical studies reported 257 cases of laboratory-confirmed JE from 1972 to 2013. JE virus (JEV) was the causative agent in 7% to 18% of cases of clinical meningitis and encephalitis combined, and 16% to 40% of clinical encephalitis cases. JE predominantly affected children under 15 years of age and 6% to 7% of cases resulted in death. Surveillance data from January 2011 to March 2014 identified 73 (15%) laboratory-confirmed JE cases out of 497 cases tested. SUMMARY: This comprehensive review demonstrates the endemicity and extensive geographic range of JE in the Philippines, and supports the use of JE vaccine in the country. Continued and improved surveillance with laboratory confirmation is needed to systematically quantify the burden of JE, to provide information that can guide prioritization of high risk areas in the country and determination of appropriate age and schedule of vaccine introduction, and to measure the impact of preventive measures including immunization against this important public health threat.

Killed oral cholera vaccines: history, development and implementation challenges.

Cholera is still a major global health problem, affecting mainly people living in unsanitary conditions and who are at risk for outbreaks of cholera. During the past decade, outbreaks are increasingly reported from more countries. From the early killed oral cholera vaccine, rapid improvements in vaccine development occurred as a result of a better understanding of the epidemiology of the disease, pathogenesis of cholera infection and immunity. The newer-generation oral killed cholera vaccines have been shown to be safe and effective in field trials conducted in cholera endemic areas. Likewise, they have been shown to be protective when used during outbreak settings. Aside from providing direct protection to vaccinated individuals, recent studies have demonstrated that these killed oral vaccines also confer indirect protection through herd immunity. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches in countries where they are most needed, especially improved water quality and sanitation, these vaccines serve as immediately available public health tools for preventing further morbidity and mortality from cholera. However, despite its availability for more than two decades, use of these vaccines has not been optimized. Although there are limitations of the currently available oral cholera vaccines, recent data show that the vaccines are safe, feasible to use even in difficult circumstances and able to provide protection in various settings. Clear identification of the areas and target population groups who will benefit from the use of the cholera vaccines will be required and strategies to facilitate accessibility and usage of these vaccines in these areas and population groups will need to be developed.