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Introduction: In Thailand, community-level poultry trade is conducted on a small-scale involving farmers and traders with many trade networks. Understanding the poultry movements may help identify different activities that farmers and traders might contribute to the spread of avian influenza. Methods: This study aimed to describe the characteristics of players involved in the poultry trade network at the northeastern border of Thailand using network analysis approaches. Mukdahan and Nakhon Phanom provinces, which border Laos, and Ubon Ratchathani province, which borders both Laos and Cambodia, were selected as survey sites. Results: Local veterinary officers identified and interviewed 338 poultry farmers and eight poultry traders in 2021. A weighted directed network identified incoming and outgoing movements of where the subdistricts traded chickens. Ninety-nine subdistricts and 181 trade links were captured. A self-looping (trader and consumer in the same subdistrict) feedback was found in 56 of 99 subdistricts. The median distance of the movements was 14.02 km (interquartile range (IQR): 6.04-102.74 km), with a maximum of 823.08 km. Most subdistricts in the network had few poultry trade connections, with a median of 1. They typically connected to 1-5 other subdistricts, most often receiving poultry from 1 to 2.5 subdistricts, and sending to 1-2 subdistricts. The subdistricts with the highest overall and in-degree centrality were located in Mukdahan province, whereas one with the highest out-degree centrality was found in Nakhon Phanom province. Discussion: The poultry movement pattern observed in this network helps explain how avian influenza could spread over the networks once introduced.
RESUMEN
BACKGROUND: Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. METHODS: This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3-5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. DISCUSSION: In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04397718. Registered on May 21, 2020.
