Detecting multi-way epistasis in family-based association studies.

The era of genome-wide association studies (GWAS) has led to the discovery of numerous genetic variants associated with disease. Better understanding of whether these or other variants interact leading to differential risk compared with individual marker effects will increase our understanding of the genetic architecture of disease, which may be investigated using the family-based study design. We present M-TDT (the multi-locus transmission disequilibrium test), a tool for detecting family-based multi-locus multi-allelic effects for qualitative or quantitative traits, extended from the original transmission disequilibrium test (TDT). Tests to handle the comparison between additive and epistatic models, lack of independence between markers and multiple offspring are described. Performance of M-TDT is compared with a multifactor dimensionality reduction (MDR) approach designed for investigating families in the hypothesis-free genome-wide setting (the multifactor dimensionality reduction pedigree disequilibrium test, MDR-PDT). Other methods derived from the TDT or MDR to investigate genetic interaction in the family-based design are also discussed. The case of three independent biallelic loci is illustrated using simulations for one- to three-locus alternative hypotheses. M-TDT identified joint-locus effects and distinguished effectively between additive and epistatic models. We showed a practical example of M-TDT based on three genes already known to be implicated in malaria susceptibility. Our findings demonstrate the value of M-TDT in a hypothesis-driven context to test for multi-way epistasis underlying common disease etiology, whereas MDR-PDT-based methods are more appropriate in a hypothesis-free genome-wide setting.

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.

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.