Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial.

Background: Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries. Methods: We conducted an open-label, randomized, outpatient, controlled trial in Thailand from October 1, 2021, to June 21, 2022, to assess whether early treatment within 48-h of symptoms onset with combinations of fluvoxamine, bromhexine, cyproheptadine, and niclosamide, given to adults with confirmed mild SARS-CoV-2 infection, can prevent 28-day clinical deterioration compared to standard care. Participants were randomly assigned to receive treatment with fluvoxamine alone, fluvoxamine + bromhexine, fluvoxamine + cyproheptadine, niclosamide + bromhexine, or standard care. The primary outcome measured was clinical deterioration within 9, 14, or 28 days using a 6-point ordinal scale. This trial is registered with ClinicalTrials.gov (NCT05087381). Findings: Among 1900 recruited, a total of 995 participants completed the trial. No participants had clinical deterioration by day 9, 14, or 28 days among those treated with fluvoxamine plus bromhexine (0%), fluvoxamine plus cyproheptadine (0%), or niclosamide plus bromhexine (0%). Nine participants (5.6%) in the fluvoxamine arm had clinical deterioration by day 28, requiring low-flow oxygen. In contrast, most standard care arm participants had clinical deterioration by 9, 14, and 28 days. By day 9, 32.7% (110) of patients in the standard care arm had been hospitalized without requiring supplemental oxygen but needing ongoing medical care. By day 28, this percentage increased to 37.5% (21). Additionally, 20.8% (70) of patients in the standard care arm required low-flow oxygen by day 9, and 12.5% (16) needed non-invasive or mechanical ventilation by day 28. All treated groups significantly differed from the standard care group by days 9, 14, and 28 (p < 0.0001). Also, by day 28, the three 2-drug treatments were significantly better than the fluvoxamine arm (p < 0.0001). No deaths occurred in any study group. Compared to standard care, participants treated with the combination agents had significantly decreased viral loads as early as day 3 of treatment (p < 0.0001), decreased levels of serum cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) as early as day 5 of treatment, and interleukin-8 (IL-8) by day 7 of treatment (p < 0.0001) and lower incidence of post-acute sequelae of COVID-19 (PASC) symptoms (p < 0.0001). 23 serious adverse events occurred in the standard care arm, while only 1 serious adverse event was reported in the fluvoxamine arm, and zero serious adverse events occurred in the other arms. Interpretation: Early treatment with these combinations among outpatients diagnosed with COVID-19 was associated with lower likelihood of clinical deterioration, and with significant and rapid reduction in the viral load and serum cytokines, and with lower burden of PASC symptoms. When started very soon after symptom onset, these repurposed drugs have high potential to prevent clinical deterioration and death in vaccinated and unvaccinated COVID-19 patients. Funding: Ped Thai Su Phai (Thai Ducks Fighting Danger) social giver group.

Exploring indoor and outdoor dust as a potential tool for detection and monitoring of COVID-19 transmission.

This study investigated the potential of using SARS-CoV-2 viral concentrations in dust as an additional surveillance tool for early detection and monitoring of COVID-19 transmission. Dust samples were collected from 8 public locations in 16 districts of Bangkok, Thailand, from June to August 2021. SARS-CoV-2 RNA concentrations in dust were quantified, and their correlation with community case incidence was assessed. Our findings revealed a positive correlation between viral concentrations detected in dust and the relative risk of COVID-19. The highest risk was observed with no delay (0-day lag), and this risk gradually decreased as the lag time increased. We observed an overall decline in viral concentrations in public places during lockdown, closely associated with reduced human mobility. The effective reproduction number for COVID-19 transmission remained above one throughout the study period, suggesting that transmission may persist in locations beyond public areas even after the lockdown measures were in place.

A qualitative study on knowledge, attitude, and practice (KAP) toward swine influenza, information on pig farms and zoonosis reporting systems in Thailand.

This qualitative study aimed to determine knowledge, attitudes, and practices (KAP) on swine influenza (SIV) among pig farm owners, pig farm workers, community leaders, public health personnel, and villagers who lived nearby pig farms in the northeastern (Nakhon Ratchasima), northern (Chiang Mai), and central (Nakhon Pathom) provinces of Thailand during May to December 2022. The qualitative information was collected from 91 respondents, including 33 individuals who participated in key informant interviews (KIIs) and 58 individuals who joined ten focus group discussions (FGDs) (5-7 persons per FGD). Our results showed that pig farmers, farm workers, and villagers lacked SIV-related knowledge and did not employ preventive measures. Some respondents had limited access to information about causes, clinical symptoms, treatment, and appropriate practices resulting in inadequate knowledge, attitudes, and practices regarding zoonotic diseases, especially SIV. Some pig farmers and farm workers reported seeking information about SIV infection from various sources; however, relevant authorities lacked dissemination of information regarding SIV to community members. The study suggested that healthcare personnel and relevant agencies should adopt a community-based approach to prevent swine influenza. This can be achieved by organizing health education and community communication interventions and involving those who have had contact with pigs or reside near pig farms. This will help increase community awareness and knowledge of swine influenza.

Tracing the transmission of mpox through wastewater surveillance in Southeast Asia.

High population density and tourism in Southeast Asia increase the risk of mpox due to frequent interpersonal contacts. Our wastewater surveillance in six Southeast Asian countries revealed positive signals for Monkeypox virus (MPXV) DNA, indicating local transmission. This alerts clinicians and helps allocate resources like testing, vaccines and therapeutics in resource-limited countries.

COVID-19 monitoring with sparse sampling of sewered and non-sewered wastewater in urban and rural communities.

Equitable SARS-CoV-2 surveillance in low-resource communities lacking centralized sewers is critical as wastewater-based epidemiology (WBE) progresses. However, large-scale studies on SARS-CoV-2 detection in wastewater from low-and middle-income countries is limited because of economic and technical reasons. In this study, wastewater samples were collected twice a month from 186 urban and rural subdistricts in nine provinces of Thailand mostly having decentralized and non-sewered sanitation infrastructure and analyzed for SARS-CoV-2 RNA variants using allele-specific RT-qPCR. Wastewater SARS-CoV-2 RNA concentration was used to estimate the real-time incidence and time-varying effective reproduction number (Re). Results showed an increase in SARS-CoV-2 RNA concentrations in wastewater from urban and rural areas 14-20 days earlier than infected individuals were officially reported. It also showed that community/food markets were "hot spots" for infected people. This approach offers an opportunity for early detection of transmission surges, allowing preparedness and potentially mitigating significant outbreaks at both spatial and temporal scales.

Multiple traces of monkeypox detected in non-sewered wastewater with sparse sampling from a densely populated metropolitan area in Asia.

The monkeypox virus is excreted in the feces of infected individuals. Therefore, there is an interest in using viral load detection in wastewater for sentinel early surveillance at a community level and as a complementary approach to syndromic surveillance. We collected wastewater from 63 sewered and non-sewered locations in Bangkok city center between May and August 2022. Monkeypox viral DNA copy numbers were quantified using real-time polymerase chain reaction (PCR) and confirmed positive by Sanger sequencing. Monkeypox viral DNA was first detected in wastewater from the second week of June 2022, with a mean copy number of 16.4 copies/ml (n = 3). From the first week of July, the number of viral DNA copies increased to a mean copy number of 45.92 copies/ml. Positive samples were Sanger sequenced and confirmed the presence of the monkeypox virus. Our study is the first to detect monkeypox viral DNA in wastewater from various locations within Thailand. Results suggest that this could be a complementary source for detecting viral DNA and predicting upcoming outbreaks.

Coronavirus seroprevalence among villagers exposed to bats in Thailand.

A serological survey of human coronavirus antibodies among villagers in 10 provinces of Thailand was conducted during 2016-2018. Serum samples (n = 364) were collected from participants from the villages and tested for coronavirus antibodies using a human coronavirus IgG ELISA kit. Our results showed that 10.44% (38/364; 21 males and 17 females) of the villagers had antibodies against human coronaviruses. The odds ratio for coronavirus positivity in the villagers in the central region who were exposed to bats was 4.75, 95% CI 1.04-21.70, when compared to that in the non-exposed villagers. The sociodemographics, knowledge, attitudes and practices (KAP) of the villagers were also recorded and analysed by using a quantitative structured questionnaire. Our results showed that 62.36% (227/364) of the villagers had been exposed to bats at least once in the past six months. Low monthly family income was statistically significant in increasing the risk for coronavirus seropositivity among the villagers (OR 2.91, 95% CI 1.13-7.49). In-depth interviews among the coronavirus-positive participants (n = 30) showed that cultural context, local norms and beliefs could influence to bat exposure activities. In conclusion, our results provide baseline information on human coronavirus antibodies and KAP regarding to bat exposure among villagers in Thailand.

Bats and belief: A sequential qualitative study in Thailand.

Bats are wildlife and distribute globally. In Thailand, there are hundreds of bat species in different locations within four regions. However, few motivations and influences for having contact with bats have been documented. This sequential qualitative study was conducted in ten provinces representing the four regions of Thailand from September 2016 to June 2017. The study was designed to obtain information on villagers' attitudes, perceptions, beliefs and cultural contexts in relation to bats. Focus group discussions (FGDs) were conducted with 305 respondents. Of these respondents, 142 (46.6%) reported coming into contact with bats through various activities, such as hunting, eating, cooking, collecting bat guano, cleaning bat feces, and finding carcasses in houses and communities. Villagers called bats by different names in different regions. They reported having been in contact with bats in different ways based on occupations, bat species, bat habitats, attitudes, perceptions, beliefs toward bats, and cultural contexts. Villagers in the northern and northeastern regions reported having regularly eaten bats. In contrast, the respondents in the central region did not eat bats due to local norms, religious beliefs, and regulations. By ethnicity, the Blu and Thai Dum groups reported coming into contact with and eating bats more often than the Thais. Our results provide evidence-based information on the human-bat interface in different regions in Thailand. The results of this qualitative study could be useful for strategic planning of proper education and interventions for bat conservation, bat contact behavior, and risk of bat-borne diseases among villagers in the future.

Risk factors for bat contact and consumption behaviors in Thailand; a quantitative study.

BACKGROUND: Bats serve as an important reservoir for emerging infectious diseases. Bat contact and consumption, which persists in Asia, poses risks for the transmission of bat-borne infections. METHODS: An analytical cross-sectional survey for risk factors associated with bat contact and consumption behaviors was conducted in ten provinces of Thailand from May 2016 to December 2017. A standardized questionnaire administered through face-to-face interviews was used to collect information from 626 villagers who lived in or nearby areas of high bat density. The questionnaire contained 23 independent variables related to sociodemographic, knowledge, attitudes, practices, and perceptions. RESULTS: The respondents (n = 626) were 285 females and 341 males, mean age of respondents was 47.58 years-old and lived in rural setting. Our results showed that 36.42% of respondents (n1 = 228) in 10 provinces reported bat contact during the past 6 months. Furthermore, 15.34% of respondents (n2 = 96) in 9 out of 10 provinces reported of having consumed bat meat in the past 6 months. Risk factors for bat contact included sex (male) (OR = 1.56, 95% CI 1.09-2.28), educational attainment (lower than secondary school) (OR = 1.45, 95% CI 1.02-2.18), and the consideration of bats as being economically beneficial to the community (OR = 3.18, 95% CI 2.03-4.97), while agriculture-related occupation (OR = 0.54, 95% CI 0.37-0.79), knowledge that it is safe to eat bats (OR = 0.58, 95% CI 0.37-0.93), practice of allowing children to play with bats (OR = 0.65, 95% CI 0.44-0.96), and attitude of feeling safe in areas where bats live (OR = 0.56, 95% CI 0.38-0.86) were statistically significant protective factors against bat contact. Risk factors for bat consumption included sex (male) (OR = 2.48, 95% CI 1.49-4.11) and educational attainment (lower than secondary school) (OR = 2.21, 95% CI 1.27-3.85), while knowledge of whether bats are safe to eat (OR = 0.04, 95% CI 0.01-0.25), knowledge of whether there are laws pertaining to hunting bats for consumption (OR = 0.35, 95% CI 0.18-0.71), and the practice of allowing children to play with bats (OR = 0.51, 95% CI 0.31-0.81) were statistically significant protective factors against bat consumption. CONCLUSIONS: This study provides a better understanding of the sociodemographic factors, knowledge, attitudes, perceptions and practices that might influence bat contact and bat consumption behaviors. Information on risk factors can be used for the development of appropriate education and communication interventions to promote proper knowledge, attitudes and practices regarding bats and bat-borne zoonotic diseases in Thailand and other areas in the Southeast Asia region with similar environmental and cultural characteristics.