Effect of single-dose, live, attenuated dengue vaccine in children with or without previous dengue on risk of subsequent, virologically confirmed dengue in Cebu, the Philippines: a longitudinal, prospective, population-based cohort study.

BACKGROUND: A three-dose dengue vaccine (CYD-TDV) was licensed for use in children aged 9 years and older starting in 2015 in several dengue-endemic countries. In 2016, the Philippine Department of Health implemented a dengue vaccination programme, which was discontinued because of safety concerns. We assessed the relative risk of developing virologically confirmed dengue among children who did or did not receive a single dose of CYD-TDV by previous dengue virus (DENV) infections at baseline classified as none, one, and two or more infections. METHODS: In this longitudinal, prospective, population-based cohort study, we enrolled healthy children (aged 9-14 years) residing in Bogo or Balamban, Cebu, Philippines, between May 2, and June 2, 2017, before a mass dengue vaccination campaign, via the Rural Health Unit in Bogo and three Rural Health Units in Balamban. We collected demographic information and sera for baseline DENV serostatus and conducted active surveillance for acute febrile illness. Children who developed acute febrile illness were identified, clinical data were collected, and blood was drawn for confirmation of dengue by RT-PCR. The primary outcome was the relative risk of developing virologically confirmed dengue among children who received or did not receive a single dose of CYD-TDV by DENV serostatus at baseline. FINDINGS: A single dose of CYD-TDV did not confer protection against virologically confirmed dengue in children who had none or one previous DENV infection at baseline. One dose conferred significant protection against hospital admission for virologically confirmed dengue among participants who had two or more previous DENV infections at baseline during the first 3 years (70%, 95% CI 20-88; p=0·017) and the entire follow-up period (67%, 19-87; p=0·016). INTERPRETATION: The risk of developing virologically confirmed dengue after a single dose of CYD-TDV varied by baseline DENV serostatus. Since the study assessed the effect of only a single dose, the findings cannot inform decisions on vaccination by public health officers. However, the findings have implications for children who receive an incomplete vaccination regimen and these results should prompt more detailed analyses in future trials on dengue vaccines. FUNDING: The Philippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency, International Vaccine Institute, University of North Carolina, and US National Institute of Allergy and Infectious Diseases.

Safety of primary immunization with a DTwP-HBV/Hib vaccine in healthy infants: a prospective, open-label, interventional, phase IV clinical study.

OBJECTIVE: This study aimed to assess the safety of a fully liquid DTwP-HBV/Hib pentavalent vaccine (EupentaTM) based on the occurrence of adverse events (AEs) following vaccination. METHODS: This was a prospective, open-label, single-arm, interventional phase IV study. A single intramuscular injection of the study vaccine was administered to infants at approximately 6, 10, and 14 weeks of age, and an end-of-study follow-up visit was scheduled at 18 weeks. RESULTS: In all, 3000 subjects were enrolled and received at least one dose of the study vaccine. Of these, 2717 (90.6%) experienced at least one AE. Immediate reactions, solicited and unsolicited AEs were respectively identified in 224 (7.5%), 2,652 (88.4%), and 1,099 (36.6%) subjects. The most prevalent solicited and unsolicited AEs comprised pain/tenderness and upper respiratory tract infection, respectively. Most AEs were mildly or moderately severe. Forty-one (1.4%) subjects had at least one serious AE (SAE); of these, two (0.1%) had two SAEs each, considered related to the study vaccine. Six (0.2%) subjects died due to unsolicited AEs, none of which were considered related to the study vaccine. No AEs were reported at the end-of-study follow-up visit. CONCLUSIONS: The study vaccine  had a safety profile similar to that reported in a previous clinical study, and did not result in an increased risk of AEs known to be associated with DTwP-based vaccines or previously unrecognized SAEs.

Novel Assay to Measure Seroprevalence of Zika Virus in the Philippines.

Zika virus (ZIKV) is a member of the Flaviviridae family, which includes other clinically notable viruses such as the 4 dengue virus serotypes (DENV-1-4). Distinguishing DENVs from ZIKV using the established serologic assays widely used for monitoring DENV transmission is difficult because of antibody cross-reactivity between these closely related flaviviruses. We describe a modified and improved recombinant envelope domain III-based serologic assay for detecting ZIKV type-specific antibodies in regions with endemic DENV transmission. When the assay was used to measure ZIKV seroprevalence in 2017 among children 9-14 years of age living in a region of the Philippines with endemic DENV transmission, we observed a ZIKV seroprevalence of 18%. Investigators should consider using the ZIKV envelope domain III-based assay, which is simple and readily adaptable for use in standard clinical and public health laboratories, to assess ZIKV seroprevalence in areas with endemic DENV transmission.

Effectiveness of a single-dose mass dengue vaccination in Cebu, Philippines: A case-control study.

BACKGROUND: Dengue fever is an important public health problem in the Philippines. In April 2016, the Department of Health launched a three-dose school based dengue vaccination program of nine- to fourteen-year-old children in three regions with the highest number of dengue cases using CYD-TDV (Dengvaxia, Sanofi Pasteur). In July 2017, a community-based dengue vaccination program was implemented in Cebu province. The program was discontinued in December 2017 amidst public controversy, after the first dose had been administered. We assessed the effectiveness of a single dose of CYD-TDV against hospitalized virologically confirmed dengue (VCD). METHODS: We conducted a case-control study in Cebu province following the dengue mass vaccination. Children who were nine to fourteen years of age during the mass vaccination and subsequently admitted to any of four participating public hospitals with suspected dengue were enrolled in the study as cases. Blood for RT-PCR and clinical and socio-demographic information were obtained. To estimate the level of vaccine protection, vaccination status was compared between children with hospitalized virologically confirmed dengue and controls of the same six-year age-group as the cases, matched on sex, neighborhood and time of occurrence of cases. FINDINGS: We enrolled 490 cases and 980 controls. Receipt of one dose of CYD-TDV was associated with 26% (95 % CI, -2 to 47%; p = 0 0675) overall protection against hospitalized virologically confirmed dengue and 51% (95 % CI, 23 to 68; p = 0 0016) protection against dengue with warning signs. INTERPRETATION: A single dose of CYD-TDV given to nine to fourteen-year-old children through a community-based mass vaccination program conferred protection against dengue with warning signs and severe dengue but we were unable to conclude on protection against milder illness.

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.

Evaluation of a new point-of-care test to determine prior dengue infection for potential use in pre-vaccination screening.

OBJECTIVE: Vaccination with the first licensed dengue vaccine is recommended only for those who have had previous infection with dengue virus (DENV). A point-of-care test with the desired sensitivity of 95% and specificity of 98% could facilitate pre-vaccination screening. We evaluated a newly developed, automated dengue immunoglobulin fluorescence immunoassay for determining dengue serostatus. METHODS: We used serum samples collected just prior to a mass dengue vaccination in Cebu, Philippines. Healthy children residing in Bogo and Balamban who would be 9-14 years old at the time of the mass dengue vaccination were eligible to participate. We evaluated the ichroma™ II dengue fluorescence immunoassay (Boditech Med Incorporated, Gang-won-do, Republic of Korea) using a neutralization test (NT) as the reference assay. RESULTS: We enrolled 2996 children (mean age 10.39 years, 51.7% female) in the cohort and included a subsample of 1000 (mean age 10.56 years, 54.4% female) in this study. Of the 1000 children, 86/1000 (8.6%) tested seronegative and 914/1000 (91.4%) seropositive for DENV antibodies by neutralization testing. Compared with the NT, the dengue IgG fluorescence immunoassay had an overall specificity of 90.7% (95%CI: 82.5-95.9%) and a sensitivity of 91.8% (95%CI: 89.8-93.5%) for determining dengue seropositivity. The sensitivity declined to 51.2% (42.3-61.0%) for the detection of the subset with a monotypic dengue profile. CONCLUSION: The insufficient specificity and sensitivity (particularly in the detection of a previous monotypic dengue infection) would render the test, in its current state, inadequate for pre-vaccination screening. Considering its user-friendly interphase and possibility of point-of-care use, the test could be further developed and validated to improve its performance characteristics.

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.

Performance of Dried Blood Spots Compared with Serum Samples for Measuring Dengue Seroprevalence in a Cohort of Children in Cebu, Philippines.

Dengue seroprevalence data are useful for understanding epidemiologic trends and transmission dynamics, and for making decisions about implementation of dengue control programs. A logistical challenge to seroprevalence surveys is the collection and transport of serum samples. For conducting large and repeated dengue serosurveys, dried blood spots (DBS) would allow easier sample collection, shipment, transport, and storage than standard serum collection methods. Further evidence is needed to understand how well DBS performs compared with standard serum collection methods in laboratory assays. We evaluated the detection of anti-dengue antibodies by IgG indirect ELISA when using DBS compared with sera. Specimens were collected from healthy children in Cebu, Philippines, who would be 9-14 years of age at the time of a mass dengue vaccination program. Using an ELISA index value cutoff of 0.9, 1,285/1,488 (86.4%) of the DBS were seropositive and 203 (13.6%) were seronegative, compared with 1,292/1,488 (86.8%) seropositive and 196 (13.2%) seronegative serum samples. Compared with sera, the DBS method had a 98.3% sensitivity, 92.4% specificity, 98.9% positive predictive value, and 89.2% negative predictive value. Considering the advantages in terms of sample collection, shipment, and storage, DBS sampling may be appropriate for dengue population serosurveys.

Determining dengue virus serostatus by indirect IgG ELISA compared with focus reduction neutralisation test in children in Cebu, Philippines: a prospective population-based study.

BACKGROUND: Detection of dengue virus antibodies is important for understanding future dengue virus risk and for prevaccination screening. We aimed to evaluate the performance of a dengue IgG indirect ELISA in determining dengue seroprevalence in a cohort of children in the Philippines, using a focus reduction neutralisation test (FRNT) as the reference test. METHODS: In this prospective population-based cohort study, we enrolled healthy children residing in Bogo or Balamban, Cebu, Philippines, who were to be aged 9-14 years at the time of a mass dengue vaccination campaign. Sera were collected from participants and batch tested by indirect IgG ELISA and FRNT. The primary endpoint was dengue seroprevalence in the cohort, detected by ELISA, and validated by that detected by reference FRNT. This study is registered with ClinicalTrials.gov, NCT03465254. FINDINGS: We collected 2996 serum samples between May 2, and June 2, 2017, and we tested each sample with IgG ELISA. Using 1961 samples (65·5%) that were tested with FRNT, and 1035 samples (34·5%) with imputed results, we found that 320 (10·7%) of 2996 children were dengue naive and 2676 (89·3%) were seropositive for previous dengue virus infection. Based on the 1961 non-imputed FRNT results classified as dengue seronegative or seropositive, the ELISA (with a 0·9 index value cutoff) showed 95·2% sensitivity, 93·4% specificity, 6·6% false positivity, and 4·8% false negativity. However, sensitivity of the ELISA was poor (77·1%) among children with immunity to just one dengue virus serotype. Of the 11 sera that were false positive with ELISA, seven samples (63·6%) were seropositive for Zika virus or Japanese encephalitis virus with FRNT. INTERPRETATION: Most children (89·3%) assessed in our study and eligible to participate in the mass dengue vaccination campaign were seropositive for previous dengue virus infection. Compared with FRNT, ELISA had high sensitivity and specificity (>90%), but the false-negative and false-positive rates makes the test suboptimal for prevaccination screening. Individuals who are falsely identified as seropositive by dengue IgG ELISA and then vaccinated might be at risk of developing severe disease during a subsequent exposure to wild-type dengue virus. Those with a monotypic profile would benefit the most from vaccination, but the sensitivity of the IgG ELISA was much lower in this group than in those with a multitypic profile. FUNDING: Philippine Department of Health, Hanako Foundation, WHO, Swedish International Development Cooperation Agency through the International Vaccine Institute, and University of North Carolina, Chapel Hill, NC, USA.

Japanese encephalitis vaccination in the Philippines: A cost-effectiveness analysis comparing alternative delivery strategies.

INTRODUCTION: Japanese encephalitis (JE) is a mosquito-borne viral infection of the brain that can cause permanent brain damage and death. In the Philippines, efforts are underway to deliver a live attenuated JE vaccine (CD-JEV) to children under five years of age (YOA), who are disproportionately infected. Multiple vaccination strategies are being considered. METHODS: We conducted a cost-effectiveness analysis comparing three vaccination strategies to the current state of no vaccination from the societal and government perspectives: (1) national routine vaccination only, (2) sub-national campaign followed by national routine, and (3) national campaign followed by national routine. We developed a Markov model to estimate impact of vaccination or no vaccination over the child's lifetime horizon, assuming an annual incidence of 10.6 cases per 100,000. Costs of illness ($859/case), vaccine ($0.50/dose), routine vaccination ($0.95/dose), and campaign vaccination ($0.98/dose) were based on hospital financial records, expert opinion and literature. The societal perspective included transportation and opportunity costs of caregiver time, in addition to costs incurred by the health system. RESULTS: JE vaccination via national campaign followed by national routine delivery was the most cost-effective strategy modeled with a cost per disability adjusted life year (DALY) averted of $233 and $29 from the government and societal perspectives, respectively. Results were similar for other delivery strategies with cost/DALY ranging from $233 to $265 from the government perspective and $29-$57 from the societal perspective. JE vaccination was projected to prevent 27,856-37,277 cases, 5571-7455 deaths, and 173,233-230,704 DALYs among children under five over 20 consecutive birth cohorts. Total incremental costs of vaccination versus no vaccination over 20 birth cohorts were $6.6-$9.8 million from the societal perspective ($230 K-$440 K annually) and $45.9-$53.9 million ($2.2 M-$2.7 M annually) from the governmental perspective. CONCLUSION: Vaccination with CD-JEV in the Philippines is projected to be cost-effective, reducing long-term costs associated with JE illness and improving health outcomes compared to no vaccination.

Cholera in selected countries in Asia.

INTRODUCTION: Although the current pandemic of cholera originated in Asia, reports of cholera cases and outbreaks in the region are sparse. To provide a sub-regional assessment of cholera in South and Southeast Asia, we collated published and unpublished data from existing surveillance systems from Bangladesh, Cambodia, India, Malaysia, Nepal, Pakistan, Philippines, Thailand and Vietnam. METHODS: Data from existing country surveillance systems on diarrhea, acute watery diarrhea, suspected cholera and/or confirmed cholera in nine selected Asian countries (Bangladesh, Cambodia, India, Malaysia, Nepal, Pakistan, Philippines, Thailand and Vietnam) from 2011 to 2015 (or 2016, when available) were collated. We reviewed annual cholera reports from WHO and searched PubMed and/or ProMED to complement data, where information is not completely available. RESULTS: From 2011 to 2016, confirmed cholera cases were identified in at least one year of the 5- or 6-year period in the countries included. Surveillance for cholera exists in most countries, but cases are not always reported. India reported the most number of confirmed cases with a mean of 5964 cases annually. The mean number of cases per year in the Philippines, Pakistan, Bangladesh, Malaysia, Nepal and Thailand were 760, 592, 285, 264, 148 and 88, respectively. Cambodia and Vietnam reported 51 and 3 confirmed cholera cases in 2011, with no subsequent reported cases. DISCUSSION AND CONCLUSION: We present consolidated results of available surveillance in nine Asian countries and supplemented these with publication searches. There is paucity of readily accessible data on cholera in these countries. We highlight the continuing existence of the disease even in areas with improved sanitation and access to safe drinking water. Continued vigilance and improved surveillance in countries should be strongly encouraged.

Age-related supportive care needs of women with gynaecological cancer: A qualitative exploration.

Women with gynaecological cancer (GC) experience significant morbidity with associated needs for support, not all of which are currently met by the current system. Types and levels of unmet needs vary across age and the care continuum. This study aimed to identify the shared and unique supportive care needs of younger and older GC patients and survivors to inform improved supportive care. Nineteen younger and ten older women, 3 months to 5 years post a GC diagnosis, were purposively recruited during active treatment, and at early and extended survivorship. Audiotaped and transcribed semi-structured interviews were thematically analysed to establish areas of needs. GC patients reported nine shared needs relating to support, isolation, uncertainty, information, asking questions, escape from illness, advocacy, loss and finding meaning. Younger patients reported unique needs related to the impact of treatment-induced menopause. There is a need for a systematic screening process to identify women who require and want additional help, to ensure appropriate and timely assistance or referrals are provided. Identification of needs will allow health professionals to provide relevant and timely information and support services, resulting in improved quality of life for women affected by GC.

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.

Feasibility of a Comprehensive Targeted Cholera Intervention in The Kathmandu Valley, Nepal.

A comprehensive targeted intervention (CTI) was designed and deployed in the neighborhoods of cholera cases in the Kathmandu Valley with the intent of reducing rates among the neighbors of the case. This was a feasibility study to determine whether clinical centers, laboratories, and field teams were able to mount a rapid, community-based response to a case within 2 days of hospital admission. Daily line listings were requested from 15 participating hospitals during the monsoon season, and a single case initiated the CTI. A standard case definition was used: acute watery diarrhea, with or without vomiting, in a patient aged 1 year or older. Rapid diagnostic tests and bacterial culture were used for confirmation. The strategy included household investigation of cases; water testing; water, sanitation, and hygiene (WASH) intervention; and health education. A CTI coverage survey was conducted 8 months postintervention. From June to December of 2016, 169 cases of Vibrio cholerae O1 were confirmed by bacterial culture. Average time to culture result was 3 days. On average, the CTI Rapid Response Team (RRT) was able to visit households 1.7 days after the culture result was received from the hospital (3.9 days from hospital admission). Coverage of WASH and health behavior messaging campaigns were 30.2% in the target areas. Recipients of the intervention were more likely to have knowledge of cholera symptoms, treatment, and prevention than non-recipients. Although the RRT were able to investigate cases at the household within 2 days of a positive culture result, the study identified several constraints that limited a truly rapid response.

Patient, client, consumer, survivor or other alternatives? A scoping review of preferred terms for labelling individuals who access healthcare across settings.

OBJECTIVES: Use of the term 'patient' has been recently debated, compared with alternatives including 'consumer' and 'client'. This scoping study aimed to provide an integrated view of preferred labels across healthcare contexts and countries to clarify labelling preferences of individuals accessing healthcare. DESIGN: Scoping study. DATA SOURCES: A preliminary literature search using GoogleScholar, Medline, Embase and PsycINFO found 43 key papers discussing terminology for labelling individuals accessing healthcare services. We then used citation chaining with PubMed and GoogleScholar to identify studies discussing term preferences among healthcare recipients. ELIGIBILITY CRITERIA: No date limits were applied, and all healthcare settings were considered. Primary research studies examining terminology preferences of individuals accessing healthcare, published in peer-reviewed journals were eligible. DATA EXTRACTION AND SYNTHESIS: All authors extracted data regarding preferred term and study characteristics, and assessed reporting quality of the studies using criteria relevant to our design. RESULTS: We identified 1565 articles, of which 47 met inclusion criteria. Six articles that examined preference for personal address (eg, first name) were excluded. Of the remaining 41 studies, 33 examined generic terms ('patient', 'client', 'consumer') and 8 focused on cancer survivorship. Of the 33 examining generic terms, 27 reported a preference for 'patient' and four for 'client'. Samples preferring 'client' were typically based in mental health settings and conducted in the USA. Of the eight cancer survivorship studies, five found a preference for 'survivor', and three 'someone who had had cancer'. CONCLUSIONS: Overall, healthcare recipients appear to prefer the term 'patient', with few preferring 'consumer'. Within general clinical and research contexts, it therefore seems appropriate to continue using the label 'patient' in the absence of knowledge about an individual's preferences. Reasons for preferences (eg, familiarity, social identity) and the implications of labelling for healthcare have not been investigated adequately, necessitating future empirical (including qualitative) research.

Prospects for rotavirus vaccine introduction in the Philippines: Bridging the available evidence into immunization policy.

Rotavirus (RV) diarrhea is one of the most common cause of childhood morbidity and mortality in the world. The World Health Organization has recommended RV vaccines' use in national immunization programs since 2009. However, access to vaccines remain limited, particularly for most low- and middle-income countries where the burden of the disease is high. The Philippines is a lower-middle income country in Asia where RV vaccination remains limited. Recent studies in the Philippines indicate an estimated vaccine effectiveness of 60% against RV hospitalization, and a 50-60% reduction of all cause diarrhea among children aged under 5 within the population. Furthermore, we estimate that 225 rotavirus cases can be prevented per 1000 children vaccinated against RV. This information will be crucial as policymakers decide on expanding RV vaccination nationwide.

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.

Effectiveness of monovalent rotavirus vaccine in the Philippines.

Rotavirus (RV) is an important cause of diarrheal disease particularly in children aged under 5 years. Monovalent RV vaccine (RVV) was selectively introduced in 2012 in the Philippines and in July 2014 was introduced in the public health program of a province. Two RVV doses are recommended at 6 and 10 weeks of age. We conducted a test negative case-control evaluation to assess the effectiveness of RVV when given in a routine public health program in the Philippines. From September 2014 to August 2017, 967 children aged <5 years were hospitalized with diarrhea and of these, we enrolled 600 who were eligible to have received RVV and provided stool specimens for testing. Among children ≥8 months of age who were age-eligible to have received RVV, at least one dose of RVV had an adjusted vaccine effectiveness (VE) against RV hospitalization of 60% (95% confidence interval, CI: 24%, 79%), and against severe rotavirus diarrhea, VE was 64% (95% CI: 11%, 85%). These findings support the introduction of RVV into routine public health use in the Philippines. However, other factors such as costs, cost-effectiveness and operational issues must be considered prior to adoption of the vaccine into the countries' public immunization program.

Clinical anxiety disorders in the context of cancer: A scoping review of impact on resource use and healthcare costs.

Prevalence of clinical anxiety among patients with cancer is higher than the general population. Clinical anxiety in people with other medical conditions is associated with greater healthcare resource use and costs. This scoping review describes the evidence relating to costs associated with clinical anxiety in cancer populations. We conducted searches of online databases Medline, Embase, Cinahl, National Health Service Economic Evaluation Database (NHS-EED) and Cochrane Library of systematic reviews to identify studies published between 2006 and 2017 that included healthcare cost in terms of monetary or health service utilisation variables. Of 411 records screened, six studies met inclusion criteria. Only one study used formal diagnostic criteria to identify clinical anxiety. The healthcare system perspective was most common, with direct costs such as medications, hospital visits, type of therapy and use of mental health services reported. All studies found anxiety was related to increased costs/resource use; however, methodological differences mean specific costs and potential impact of interventions on resource use remain relatively unquantified. Despite the prevalence of clinical anxiety, there is little data on the economic impact on health service costs and utilisation. Future studies quantifying the true cost are urgently needed to inform healthcare service planning and delivery, and quality improvement initiatives.