Competitive evolution of H1N1 and H3N2 influenza viruses in the United States: A mathematical modeling study.

Seasonal influenza causes vast public health and economic impact globally. The prevention and control of the annual epidemics remain a challenge due to the antigenic evolution of the viruses. Here, we presented a novel modeling framework based on changes in amino acid sequences and relevant epidemiological data to retrospectively investigate the competitive evolution and transmission of H1N1 and H3N2 influenza viruses in the United States during October 2002 and April 2019. To do so, we estimated the time-varying disease transmission rate from the reported influenza cases and the time-varying antigenic change rate of the viruses from the changes in amino acid sequences. By incorporating the time-varying antigenic change rate into the transmission models, we found that the models could capture the evolutionary transmission dynamics of influenza viruses in the United States. Our modeling results also showed that the antigenic change of the virus plays an essential role in seasonal influenza dynamics.

A remotely sensed flooding indicator associated with cattle and buffalo leptospirosis cases in Thailand 2011-2013.

BACKGROUND: Leptospirosis is an important zoonotic disease worldwide, caused by spirochetes bacteria of the genus Leptospira. In Thailand, cattle and buffalo used in agriculture are in close contact with human beings. During flooding, bacteria can quickly spread throughout an environment, increasing the risk of leptospirosis infection. The aim of this study was to investigate the association of several environmental factors with cattle and buffalo leptospirosis cases in Thailand, with a focus on flooding. METHOD: A total of 3571 urine samples were collected from cattle and buffalo in 107 districts by field veterinarians from January 2011 to February 2013. All samples were examined for the presence of leptospirosis infection by loop-mediated isothermal amplification (LAMP). Environmental data, including rainfall, percentage of flooded area (estimated by remote sensing), average elevation, and human and livestock population density were used to build a generalized linear mixed model. RESULTS: A total of 311 out of 3571 (8.43%) urine samples tested positive by the LAMP technique. Positive samples were recorded in 51 out of 107 districts (47.66%). Results showed a significant association between the percentage of the area flooded at district level and leptospirosis infection in cattle and buffalo (p = 0.023). Using this data, a map with a predicted risk of leptospirosis can be developed to help forecast leptospirosis cases in the field. CONCLUSIONS: Our model allows the identification of areas and periods when the risk of leptospirosis infection is higher in cattle and buffalo, mainly due to a seasonal flooding. The increased risk of leptospirosis infection can also be higher in humans too. These areas and periods should be targeted for leptospirosis surveillance and control in both humans and animals.

Seasonal patterns of influenza incidence and the influence of meteorological and air pollution factors in Thailand during 2009-2019.

Influenza, an acute respiratory illness, remains a significant public health challenge, contributing substantially to morbidity and mortality worldwide. Its seasonal prevalence exhibits diversity across regions with distinct climates. This study aimed to explore the seasonal patterns of influenza and their correlation with meteorological and air pollution factors across six regions of Thailand. We conducted an analysis of monthly average temperature, relative humidity, precipitation, PM10, NO2, O3 concentrations, and influenza incidence data from 2009 to 2019 using wavelet analysis. Our findings reveal inconsistent biannual influenza prevalence patterns throughout the study period. The biannual pattern emerged during 2010-2012 across all regions but disappeared during 2013-2016. However, post-2016, the biannual cycles resurfaced, with peaks occurring during the rainy and winter seasons in most regions, except for the southern region. Wavelet coherence reveals that relative humidity can be the main influencing factor for influenza incidence over a one-year period in the northern, northeastern, central, Bangkok-metropolitan, and eastern regions, not in the southern region during 2010-2012 and 2016-2018. Similarly, precipitation can drive the influenza incidence at the same period for the northeastern, central, Bangkok-metropolitan, and eastern regions. PM10 concentration can influence influenza incidence over a half-year period in the northeastern, central, Bangkok-metropolitan, and eastern regions of Thailand during certain years. These results enhance our understanding of the temporal dynamics of influenza seasonality influenced by weather conditions and air pollution over the past 11 years. Such knowledge is invaluable for resource allocation in clinical settings and informing public health strategies, particularly in navigating Thailand's climatic complexities.

Vaccination strategies impact the probability of outbreak extinction: A case study of COVID-19 transmission.

Mass vaccination has proven to be an effective control measure for mitigating the transmission of infectious diseases. Throughout history, various vaccination strategies have been employed to control infections and terminate outbreaks. In this study, we utilized the transmission of COVID-19 as a case study and constructed a stochastic age-structured compartmental model to investigate the effectiveness of different vaccination strategies. Our analysis focused on estimating the outbreak extinction probability under different vaccination scenarios in both homogeneous and heterogeneous populations. Notably, we found that population heterogeneity can enhance the likelihood of outbreak extinction at varying levels of vaccine coverage. Prioritizing vaccinations for individuals with higher infection risk was found to maximize outbreak extinction probability and reduce overall infections, while allocating vaccines to those with higher mortality risk has been proven more effective in reducing deaths. Moreover, our study highlighted the significance of booster doses as the vaccine effectiveness wanes over time, showing that they can significantly enhance the extinction probability and mitigate disease transmission.

LSTM-Powered COVID-19 prediction in central Thailand incorporating meteorological and particulate matter data with a multi-feature selection approach.

The COVID-19 pandemic has significantly impacted public health and necessitated urgent actions to mitigate its spread. Monitoring and predicting the outbreak's progression have become vital to devise effective strategies and allocate resources efficiently. This study presents a novel approach utilizing Multivariate Long Short-Term Memory (LSTM) to analyze and predict COVID-19 trends in Central Thailand, particularly emphasizing the multi-feature selection process. To consider a comprehensive view of the pandemic's dynamics, our research dataset encompasses epidemiological, meteorological, and particulate matter features, which were gathered from reliable sources. We propose a multi-feature selection technique to identify the most relevant and influential features that significantly impact the spread of COVID-19 in the region to enhance the model's performance. Our results highlight that relative humidity is the key factor driving COVID-19 transmission in Central Thailand. The proposed multi-feature selection technique significantly improves the model's accuracy, ensuring that only the most informative variables contribute to the predictions, avoiding the potential noise or redundancy from less relevant features. The proposed LSTM model demonstrates its capability to forecast COVID-19 cases, facilitating informed decision-making for public health authorities and policymakers.

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.

Modeling vaccination strategies with limited early COVID-19 vaccine access in low- and middle-income countries: A case study of Thailand.

Low- and middle-income countries faced significant challenges in accessing COVID-19 vaccines during the early stages of the pandemic. In this study, we utilized an age-structured modeling approach to examine the implications of various vaccination strategies, vaccine prioritization, and vaccine rollout speeds in Thailand, an upper-middle-income country experiencing vaccine shortages during the early stages of the pandemic. The model directly compares the effectiveness of several vaccination strategies, including the heterologous vaccination where CoronaVac (CV) vaccine was administered as the first dose, followed by ChAdOx1 nCoV-19 (AZ) vaccine as the second dose, under varying disease transmission dynamics. We found that the traditional AZ homologous vaccination was more effective than the CV homologous vaccination, regardless of disease transmission dynamics. However, combining CV and AZ vaccines via either parallel homologous or heterologous vaccinations was more effective than relying solely on AZ homologous vaccination. Additionally, prioritizing vaccination for the elderly aged 60 years and above was the most effective way to reduce mortality when community transmission is well-controlled. On the other hand, prioritizing workers aged 20-59 was most effective in lowering COVID-19 cases, irrespective of the transmission dynamics. Lastly, despite the vaccine prioritization strategy, rapid vaccine rollout speeds were crucial in reducing COVID-19 infections and deaths. These findings suggested that in low- and middle-income countries where early access to high-efficacy vaccines might be limited, obtaining any accessible vaccines as early as possible and using them in parallel with other higher-efficacy vaccines might be a better strategy than waiting for and relying solely on higher-efficacy vaccines.

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.

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.

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.

Estimation of Excess All-Cause Mortality Due to COVID-19 in Thailand.

Thailand has experienced the most prominent COVID-19 outbreak in 2021, resulting in a new record for COVID-19 cases and deaths. To assess the influence of the COVID-19 outbreak on mortality, we estimated excess all-cause and pneumonia mortality in Thailand during the COVID-19 outbreak from April to October 2021. We used mortality from the previous 5 years to estimate the baseline number of deaths using generalized linear mixed models. The models were adjusted for seasonality and demographics. We found that, during the outbreak in 2021, there was a significant rise in excess fatalities, especially in the older age groups. The estimated cumulative excess death was 14.3% (95% CI: 8.6-18.8%) higher than the baseline. The results also showed that the excess deaths in males were higher than in females by approximately 26.3%. The excess deaths directly caused by the COVID-19 infections accounted for approximately 75.0% of the all-cause excess deaths. Furthermore, excess pneumonia deaths were also found to be 26.2% (95% CI: 4.8-46.0%) above baseline.

Spatial-temporal patterns and risk factors for human leptospirosis in Thailand, 2012-2018.

Leptospirosis is a globally important zoonotic disease. The disease is particularly important in tropical and subtropical countries. Infections in humans can be caused by exposure to infected animals or contaminated soil or water, which are suitable for Leptospira. To explore the cluster area, the Global Moran's I index was calculated for incidences per 100,000 population at the province level during 2012-2018, using the monthly and annual data. The high-risk and low-risk provinces were identified using the local indicators of spatial association (LISA). The risk factors for leptospirosis were evaluated using a generalized linear mixed model (GLMM) with zero-inflation. We also added spatial and temporal correlation terms to take into account the spatial and temporal structures. The Global Moran's I index showed significant positive values. It did not demonstrate a random distribution throughout the period of study. The high-risk provinces were almost all in the lower north-east and south parts of Thailand. For yearly reported cases, the significant risk factors from the final best-fitted model were population density, elevation, and primary rice crop arable areas. Interestingly, our study showed that leptospirosis cases were associated with large areas of rice production but were less prevalent in areas of high rice productivity. For monthly reported cases, the model using temperature range was found to be a better fit than using percentage of flooded area. The significant risk factors from the model using temperature range were temporal correlation, average soil moisture, normalized difference vegetation index, and temperature range. Temperature range, which has strongly negative correlation to percentage of flooded area was a significant risk factor for monthly data. Flood exposure controls should be used to reduce the risk of leptospirosis infection. These results could be used to develop a leptospirosis warning system to support public health organizations in Thailand.

Modeling of the combined dynamics of leptospirosis transmission and seroconversion in herds.

Leptospirosis is a zoonotic disease-causing illness in both humans and animals resulting in related economic impacts due to production loss as well as prevention and control efforts. Several mathematical models have been proposed to study the dynamics of infection but none of them has so far taken into account the dynamics of seroconversion. In this study, we have developed a general framework, based on the kinetic model for animal leptospirosis, that combines both the antibody (exposure marker) and infection dynamics to simultaneously follows both seroconversion and infection status of leptospirosis in a herd population. It is a stochastic compartmental model (for transition rates) with time delay (for seroconversion) which describes the progression of infection by a SEIRS (susceptible, exposed, infected, removed and susceptible) approach and seroconversion by four-state antibody kinetics (antibody negative and three antibody positive states of different antibody levels). The model shows that it is possible to assess and follow both seroconversion and infection status through the prism of diagnostic testing. Such an approach of combined kinetics could prove very useful to assist the competent authorities in their analyzes of epidemic situations and in the implementation of strategies for controlling and managing the associated risks.

Modelling the effectiveness of intervention strategies to control COVID-19 outbreaks and estimating healthcare demand in Germany.

OBJECTIVES: An outbreak of the novel coronavirus in December 2019 caused a worldwide pandemic. This disease also impacts European countries, including Germany. Without effective medicines or vaccines, non-pharmaceutical interventions are the best strategy to reduce the number of cases. STUDY DESIGN: A deterministic model was simulated to evaluate the number of infectious and healthcare demand. METHOD: Using an age-structured SEIR model for the COVID-19 transmission, we project the COVID-19-associated demand for hospital and ICU beds within Germany. We estimated the effectiveness of different control measures, including active case-finding and quarantining of asymptomatic persons, self-isolation of people who had contact with an infectious person, and physical distancing, as well as a combination of these control measures. RESULTS: We found that contact tracing could reduce the peak of ICU beds as well as mass testing. The time delay between diagnosis and self-isolation influences the control measures. Physical distancing to limit the contact rate would delay the peak of the outbreak, which results in the demand for ICU beds being below the capacity during the early outbreak. CONCLUSIONS: Our study analyzed several scenarios in order to provide policymakers that face the pandemic of COVID-19 with insights into the different measures available. We highlight that the individuals who have had contact with a virus-positive person must be quarantined as soon as possible to reduce contact with possible infectious cases and to reduce transmission. Keeping physical distance and having fewer contacts should be implemented to prevent overwhelming ICU demand.

The effects of flooding and weather conditions on leptospirosis transmission in Thailand.

The epidemic of leptospirosis in humans occurs annually in Thailand. In this study, we have developed mathematical models to investigate transmission dynamics between humans, animals, and a contaminated environment. We compared different leptospire transmission models involving flooding and weather conditions, shedding and multiplication rate in a contaminated environment. We found that the model in which the transmission rate depends on both flooding and temperature, best-fits the reported human data on leptospirosis in Thailand. Our results indicate that flooding strongly contributes to disease transmission, where a high degree of flooding leads to a higher number of infected individuals. Sensitivity analysis showed that the transmission rate of leptospires from a contaminated environment was the most important parameter for the total number of human cases. Our results suggest that public education should target people who work in contaminated environments to prevent Leptospira infections.

Leptospirosis research: fast, easy and reliable enumeration of mobile leptospires.

Leptospirosis caused by Leptospira interrogans is the most widespread zoonosis and a major public health problem worldwide. Based on light-scattering and absorption, quantification of leptospires using UV-VIS spectroscopy was used as an indirect counting technique by measuring the optical density and comparing this to automated direct counting using a counting chamber in combination with imaging and analyzing software. Two serovars, Bangkok and Copenhagenii, from log-phase growth were used for the establishment of standard curves. They were found to be linear and slightly different in gradient for each serovar. The ease, rapidity, and reliability of these two adapted and optimized counting techniques may provide a useful alternative enumeration technique for leptospirosis research.

The Modelling of Hand, Foot, and Mouth Disease in Contaminated Environments in Bangkok, Thailand.

Hand, foot, and mouth disease (HFMD) has spread widely in a continuing endemic in Thailand. There are no specific vaccines or antiviral treatments available that specifically target HFMD. Indirect transmission via free-living viruses from the environment may influence HFMD infections because the virus can survive for long periods in the environment. In this study, a new mathematical model is proposed to investigate the effect of indirect transmission from contaminated environments and the impact of asymptomatic individuals. By fitting our model to reported data on hospitalized individuals of HFMD endemic in Bangkok, Thailand, 2016, the basic reproduction number was estimated as 1.441, which suggests that the disease will remain under current conditions. Numerical simulations show that the direct transmission from asymptomatic individuals and indirect transmission via free-living viruses are important factors which contribute to new HFMD infections. Sensitivity analysis indicates that the basic reproduction number is sensitive to the transmission rate of asymptomatic and symptomatic subgroups and indirect transmission. Our findings suggest that cleaning the environment frequently and healthcare precautions which include the reduction of direct transmission rates should be promoted as effective control strategies for preventing the HFMD spread.