Efficacy Assessment of Autodissemination Using Pyriproxyfen-Treated Ovitraps in the Reduction of Dengue Incidence in Parañaque City, Philippines: A Spatial Analysis.

Dengue is one of the most important vector-borne diseases worldwide and is a significant public health problem in the tropics. Mosquito control continues to be the primary approach to reducing the disease burden and spread of dengue virus (DENV). Aside from the traditional larviciding and adulticiding interventions, autodissemination using pyriproxyfen-treated (AD-PPF) ovitraps is one of the promising methods to complement existing vector control strategies. Our paper assessed the efficacy of AD-PPF in reducing DENV infections in two barangays in Parañaque City. Using saliva samples from the participants from both the control and intervention sites, we collected the seroprevalence data for three months in each of the two years. Spatial analysis was conducted to determine hotspot areas and identify DENV infection distributions across the trial periods. The results showed that the intervention site was identified as having a clustering of DENV infections in Month 0 of Year 1 and shifted to a random dispersion of dengue cases at the end of Month 3 in Year 2. The disappearance of the clustering of the intervention site translates to a decrease in the cases of DENV infection relative to the control site. Furthermore, we also identified that DENV transmission occurred at a small-scale level that did not go beyond 86 m. In conclusion, AD-PPF is suggested to be an effective strategy and may be used as an additional vector control approach, albeit based on this short-term implementation.

In Silico Comparative Analysis of Predicted B Cell Epitopes against Dengue Virus (Serotypes 1-4) Isolated from the Philippines.

Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1-4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1-4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1-4) Philippine isolates.

Multimer Detection System-Oligomerized Amyloid Beta (MDS-OAß): A Plasma-Based Biomarker Differentiates Alzheimer's Disease from Other Etiologies of Dementia.

With emerging amyloid therapies, documentation of the patient's amyloid status to confirm the etiology of a clinical diagnosis is warranted prior to instituting amyloid-based therapy. The Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a noninvasive blood-based biomarker utilized to measure Aß oligomerization tendency. We determined the difference in MDS-OAß ratio across the groups: (a) no cognitive impairment or subjective cognitive impairment (NCI/SCI), (b) Alzheimer's disease (AD), (c) non-AD, and (d) mixed Alzheimer's disease-Vascular dementia (AD-VaD). MDS-OAß level was not significantly different between AD and mixed AD-VaD, but both groups were significantly different from the NCI/SCI and from the non-AD group. An MDS-OAß level of >1 could potentially indicate clinical variants of AD or mixed pathology (AD-VaD).

Assessing Entomological and Epidemiological Efficacy of Pyriproxyfen-Treated Ovitraps in the Reduction of Aedes Species: A Quasi-Experiment on Dengue Infection Using Saliva Samples.

Our study assessed the impact of using ovitraps with pyriproxyfen on mosquito populations and the feasibility of using human saliva samples to test for seroconversion to dengue virus (DENV). We used a quasi-experimental research design by forming the intervention (n = 220) and the control (n = 223) groups in neighboring Taguig City, Philippines, over 4 months. Socio-demographic data, entomological indices, and IgG antibodies against DENV were measured. Associations between the implementation of ovitraps dosed with pyriproxyfen and mosquito densities (percentage positive ovitraps and container indices) and DENV seroconversion were calculated post-intervention in Months 2, 3, and 4. Among the participants recruited at baseline, 17 and 13 were seropositive for dengue (DENV) in the intervention and control groups, respectively. Both entomological indices were lower in the treated area than the control site at post-intervention Months 2, 3, and 4, but not earlier. Dengue seroconversions rates decreased in the treated population, but not significantly so. In conclusion, the use of PPF-treated ovitraps may have impacted the mosquito population, but not seroconversion rates. Compliance in providing saliva samples and the ability to detect IgG antibodies within these samples was encouraging and suggests that further studies on larger populations for longer durations are warranted.

"We Tried to Borrow Money, but No One Helped." Assessing the Three-Delay Model Factors Affecting the Healthcare Service Delivery among Dengue Patients during COVID-19 Surge in a Public Tertiary Hospital: A Convergent Parallel Mixed Methods Study.

Identification of delay barriers to care is essential for an effective and efficient healthcare service delivery. In this study, we described the delay in care among parents of the patients seeking treatment for dengue. We also examined the factors affecting the severity of dengue (dengue with warning signs; severe dengue). A convergent parallel design mixed-method approach using Key Informant Interviews (KII) and a survey guided by the Three-Delay Model were conducted among 24 respondents at the National Children's Hospital (NCH). Coding and thematic analysis using NVIVO and bivariable generalized linear models with a Poisson distribution and robust variance were utilized to analyze the KII transcripts and survey data, respectively. Results showed that financial constraints and previous dengue infection (first delay), mode of transportation, traffic density, and location (second delay), and hospital capacity (third delay) influenced the overall delay uncertainty in seeking care treatment for dengue infection. Furthermore, our bivariable analysis showed that travel time to NCH and place of residency, service given from previous health facilities, and parents' educational background were associated and played a role in the severity of dengue infection. Interventions focused on the identified factors contributing to delayed care should be made to avoid unwanted clinical outcomes.

Short-Term Cumulative Exposure to Ambient Traffic-Related Black Carbon and Blood Pressure: MMDA Traffic Enforcers' Health Study.

Exposure to traffic-related air pollution is linked with acute alterations in blood pressure (BP). We examined the cumulative short-term effect of black carbon (BC) exposure on systolic (SBP) and diastolic (DBP) BP and assessed effect modification by participant characteristics. SBP and DBP were repeatedly measured on 152 traffic enforcers. Using a linear mixed-effects model with random intercepts, quadratic (QCDL) and cubic (CCDL) constrained distributed lag models were fitted to estimate the cumulative effect of BC concentration on SBP and DBP during the 10 hours (daily exposure) and 7 days (weekly exposure) before the BP measurement. Ambient BC was related to increased BP with QCDL models. An interquartile range change in BC cumulative during the 7 days before the BP measurement was associated with increased BP (1.2% change in mean SBP, 95% confidence interval (CI), 0.1 to 2.3; and 0.5% change in mean DBP, 95% CI, -0.8 to 1.7). Moreover, the association between the 10-h cumulative BC exposure and SBP was stronger for female (4.0% change, 95% CI: 2.1-5.9) versus male and for obese (2.9% change, 95% CI: 1.0-4.8) vs. non-obese traffic enforcers. Short-term cumulative exposure to ambient traffic-related BC could bring about cardiovascular diseases through mechanisms involving increased BP.

Challenges to Mitigating the Urban Health Burden of Mosquito-Borne Diseases in the Face of Climate Change.

Cities worldwide are facing ever-increasing pressure to develop mitigation strategies for all sectors to deal with the impacts of climate change. Cities are expected to house 70% of the world's population by 2050, and developing related resilient health systems is a significant challenge. Because of their physical nature, cities' surface temperatures are often substantially higher than that of the surrounding rural areas, generating the so-called Urban Heat Island (UHI) effect. Whilst considerable emphasis has been placed on strategies to mitigate against the UHI-associated negative health effects of heat and pollution in cities, mosquito-borne diseases have largely been ignored. However, the World Health Organization estimates that one of the main consequences of global warming will be an increased burden of mosquito-borne diseases, many of which have an urban facet to their epidemiology and thus the global population exposed to these pathogens will steadily increase. Current health mitigation strategies for heat and pollution, for example, may, however, be detrimental for mosquito-borne diseases. Implementation of multi-sectoral strategies that can benefit many sectors (such as water, labor, and health) do exist or can be envisaged and would enable optimal use of the meagre resources available. Discussion among multi-sectoral stakeholders should be actively encouraged.

Dementia Incidence, Burden and Cost of Care: A Filipino Community-Based Study.

Background: In the midst of competing priorities and limited resources in low-middle-income countries (LMIC), convincing epidemiological evidence is critical for urging governments to develop national dementia plans. The majority of primary epidemiological studies on dementia are from high income countries (HIC). Implications for developing countries are typically extrapolated from these outcomes through modeling, meta-analyses, and systematic reviews. In this study, we directly assessed the incidence of dementia, disability adjusted life years (DALYs), and cost of care among community-dwelling Filipino elderly. Methods: This was a follow-up study of the prospective cohort Marikina Memory Ageing Project (MMAP). Baseline assessment was performed in 2011-2012, and follow-up was done in 2015-2016 (N = 748 at follow-up). Incident dementia was determined. Disease burden was computed using the incidence rates and DALYs. Both indirect and direct (medical and non-medical) costs of dementia care were computed. Results: The crude incidence rate was 16 (CI: 13-20) cases per 1,000 person-years (pyr) with 17 (CI: 12-21) per 1,000 pyr for females and 14 (CI: 9-21) per 1,000 pyr for males. Based on this incidence, we project an estimation of 220,632 new cases in 2030, 295,066 in 2040, and 378,461 in 2050. Disease burden was at 2,876 DALYsper 100,000 persons. The economic burden per patient was around Php 196,000 annually (i.e., ~4,070 USD, or 36.7% of average family annual income in the Philippines). The majority (86.29%) of this care expense was indirect cost attributed to estimated lost potential earning of unpaid family caregivers whereas direct medical cost accounted for only 13.48%. Conclusions: We provide the first Filipino community-based data on the incidence of dementia, DALYs, and cost of care to reflect the epidemiologic and economic impact of disease. The findings of this study serve to guide the development of a national dementia plan.

Autosomal Dominant Frontotemporal Lobar Degeneration in a Filipino Family with Progranulin Mutation.

BACKGROUND: Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia. CASE PRESENTATION: The proband is 66 years old with progressive nonfluent aphasia (PNFA)-corticobasal syndrome . We assessed 3 generations of her pedigree and found 11 affected relatives with heterogenous phenotypes, usually behavioral variant frontotemporal dementia (FTD) and PNFA. Neuroimaging showed atrophy and hypometabolism consistent with FTD syndromes. White matter hyperintensities were seen in affected members even in the absence of vascular risk factors. A GRN mutation R110X was found in 6 members, 3 with symptoms and 3 were asymptomatic. Plasma GRN was low (<112 ng/mL) in all mutation carriers. No mutations were found in microtubule-associated protein tau, APP, PSEN1, and PSEN2 genes, and all were APOE3. CONCLUSION: This is the first Filipino family with autosomal dominant FTD documented with GRN mutation. Identifying families and cohorts would contribute to therapeutic developments in an area with FTD-GRN.

Determining Filipino Normative Data for a Battery of Neuropsychological Tests: The Filipino Norming Project (FNP).

BACKGROUND: Filipino normative data for neuropsychological tests are lacking. OBJECTIVES: This study aimed to determine the Filipino normative data for the Filipino Norming Project (FNP) Neuropsychological Battery, combining the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) and the Neuropsychological Test Battery from the Uniform Dataset of Alzheimer's Disease Center (UDS-ADC). METHODS: We recruited participants 60 years and older with normal cognition (MMSE score of 25 and above and did not fulfill criteria for dementia according to DSM-IV criteria). Psychologists administered the tests to the study participants. We conducted multivariate analyses to study the effect of age, gender, and education on test performance. RESULTS: A total of 191 participants underwent the FNP Neuropsychological Test Battery. The mean age was 68.8 years (SD 5.4). The majority were female (84.1%). The mean score of ADAS-Cog was 9.98 (SD 4.74). The effect of education was prominent throughout the cognitive domains tested while the effect of age was limited to a few cognitive domains. The mean ADAS-Cog scores were 11.80 ± 4.40 for primary education, 9.93 ± 5.08 for secondary, and 8.15 ± 3.95 for tertiary. On average, women scored 2.75 points lower than men and performed better on the verbal components. Men performed better on the constructional praxis component. The same effect of education and gender was observed for the UDS-ADC. CONCLUSION: For the first time, normative data are available for the ADAS-Cog and UDS-ADC for a Filipino older population. This study stresses the importance of establishing population-specific normative data, taking into account the specific sociocultural and linguistic context of that population.

A randomized, observer-blinded, equivalence trial comparing two variations of Euvichol®, a bivalent killed whole-cell oral cholera vaccine, in healthy adults and children in the Philippines.

BACKGROUND: To contribute to the global demand for oral cholera vaccine (OCV), the production of Euvichol® was scaled up with elimination of thimerosal. To demonstrate the equivalence of the variations, a study was carried out in the Philippines. METHODS: Healthy male and female adults and children in Manila were randomized to receive two doses of Euvichol® two weeks apart from either the 100L (Comparator) or the 600L (Test) variation. Primary and secondary immunogenicity endpoints were respectively geometric mean titer (GMT) of vibriocidal antibodies (two weeks post second dose) and seroconversion rate (two weeks after each dose) against O1 Inaba, Ogawa, and O139 serogroups. The GMT of vibriocidal antibodies against O1 Inaba, Ogawa, and O139 two weeks post first dose was also measured. To show the equivalence of two variations of Euvichol®, the ratio of GMT and the difference of seroconversion rate between Test and Comparator vaccines were tested with equivalence margin of [0.5, 2.0] for GMT ratio and of 15% for seroconversion rate, respectively. Safety assessment included solicited reactogenicity within 6 days after each dose and unsolicited and serious adverse events. RESULTS: A total of 442 participants were enrolled. For the overall population, equivalence between Test and Comparator was demonstrated for vibriocidal antibody response against O1 Inaba and Ogawa serotypes and O139 serogroup in both modified intention-to-treat (mITT) and per protocol analysis, since the 95% confidence intervals (CI) of GMT to any serotypes were within the lower and upper boundary [0.5, 2.0]. Seroconversion rates after two doses also showed equivalence for O1 Inaba, Ogawa, and O139. The vaccine was safe and well tolerated, similarly between the two groups. CONCLUSION: The study results support the equivalence of the 600L Euvichol® to the 100L formulation in healthy children and adults. The 600L Euvichol® is safe and immunogenic in adults and children. ClinicalTrials.gov registration number: NCT02502331.

A randomized, non-inferiority trial comparing two bivalent killed, whole cell, oral cholera vaccines (Euvichol vs Shanchol) in the Philippines.

BACKGROUND: Currently, there are two oral cholera vaccines (OCV) that are prequalified by the World Health Organization. Both (Dukoral and Shanchol) have been proven to be safe, immunogenic, and effective. As the global supply of OCV remains limited, we assessed the safety and immunogenicity of a new low cost, killed, bivalent OCV (Euvichol) in the Philippines. METHODS: The randomized controlled trial was carried out in healthy Filipino adults and children. Two doses of either the current WHO prequalified OCV (Shanchol) or the same composition OCV being considered for WHO prequalification (Euvichol) were administered to participants. RESULTS: The pivotal study was conducted in total of 1263 healthy participants (777 adults and 486 children). No serious adverse reactions were elicited in either vaccine groups. Vibriocidal antibody responses to V. cholerae O1 Inaba following administration of two doses of Euvichol were non-inferior to those of Shanchol in adults (82% vs 76%) and children (87% vs 89%). Similar findings were observed for O1 Ogawa in adults (80% vs 74%) and children (91% vs 88%). CONCLUSION: A two dose schedule with Euvichol induces a strong vibriocidal response comparable to those elicited by the currently WHO prequalified OCV, Shanchol. Euvichol will be an oral cholera vaccine suitable for use in lower income countries, where cholera still has a significant economic and public health impact.