HCV Spread Kinetics Reveal Varying Contributions of Transmission Modes to Infection Dynamics.
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ABSTRACT:
SUBMITTER: Durso-Cain K
PROVIDER: S-EPMC8310333 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dengue is an arbovirus affecting global populations. Frequent outbreaks occur, especially in equatorial cities such as Singapore, where year-round tropical climate, large daily influx of travelers and population density provide the ideal conditions for dengue to transmit. Little work has, however, quantified the peaks of dengue outbreaks, when health systems are likely to be most stretched. Nor have methods been developed to infer differences in exogenous factors which lead to the rise and fall of dengue case counts across extreme and non-extreme periods. In this paper, we developed time varying extreme mixture (tvEM) methods to account for the temporal dependence of dengue case counts across extreme and non-extreme periods. This approach permits inference of differences in climatic forcing across non-extreme and extreme periods of dengue case counts, quantification of their temporal dependence as well as estimation of thresholds with associated uncertainties to determine dengue case count extremities. Using tvEM, we found no evidence that weather affects dengue case counts in the near term for non-extreme periods, but that it has non-linear and mixed signals in influencing dengue through tvEM parameters in the extreme periods. Using the most appropriate tvEM specification, we found that a threshold at the 70th (95% credible interval 41.1, 83.8) quantile is optimal, with extreme events of 526.6, 1052.2 and 1183.6 weekly case counts expected at return periods of 5, 50 and 75 years. Weather parameters at a 1% scaled increase was found to decrease the long-run expected case counts, but larger increases would lead to a drastic expected rise from the baseline correspondingly. The tvEM approach can provide valuable inference on the extremes of time series, which in the case of infectious disease notifications, allows public health officials to understand the likely scale of outbreaks in the long run.
| S-EPMC7595636 | biostudies-literature
Project description:The epidemic spread of infectious diseases is ubiquitous and often has a considerable impact on public health and economic wealth. The large variability in the spatio-temporal patterns of epidemics prohibits simple interventions and requires a detailed analysis of each epidemic with respect to its infectious agent and the corresponding routes of transmission. To facilitate this analysis, we introduce a mathematical framework which links epidemic patterns to the topology and dynamics of the underlying transmission network. The evolution, both in disease prevalence and transmission network topology, is derived from a closed set of partial differential equations for infections without allowing for recovery. The predictions are in excellent agreement with complementarily conducted agent-based simulations. The capacity of this new method is demonstrated in several case studies on HIV epidemics in synthetic populations: it allows us to monitor the evolution of contact behavior among healthy and infected individuals and the contributions of different disease stages to the spreading of the epidemic. This gives both direction to and a test bed for targeted intervention strategies for epidemic control. In conclusion, this mathematical framework provides a capable toolbox for the analysis of epidemics from first principles. This allows for fast, in silico modeling--and manipulation--of epidemics and is especially powerful if complemented with adequate empirical data for parameterization.
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Project description:The relationships among micro RNA-122 (miR-122) expression in the liver, hepatitis C virus (HCV) replication and hepatic damage were analyzed in three chimpanzees observed for 180 days after inoculation with HCV genotype 1a. Levels of miR-122 in the liver and serum were measured by real-time RT PCR in serial liver biopsies and serum samples. Hepatic miR-122 levels were normalized separately for each of three chimpanzees with small RNAs and microRNAs that are endogenous to the liver and are stably expressed. Two- to 4-fold rise in hepatic miR-122 levels was observed at the onset of HCV infection (the first 4 weeks) when HCV titers in the liver and serum increased rapidly in all three chimpanzees in concordance with in vitro data indicating the miR-122 significance for HCV replication. Between 10 to 14 weeks after inoculation, when hepatic and serum HCV RNA titers exceeded 3 logs and alanine aminotransferase (ALT) activity was elevated, hepatic miR-122 levels were in decline. Cumulative data derived from all three chimpanzees from 180 days of observation documented an inverse (negative) correlation between hepatic miR-122 and HCV RNA in the liver and serum and positive correlation between level of serum miR-122 and HCV replication. Subsequent rise of miR-122 level during HCV clearance and ALT normalization suggested a tri-phasic occurrence of the relationship among hepatic miR-122 expression, HCV replication and hepatic destruction, which was the most apparent in one chimpanzee but less evident in two other animals. In vivo kinetics of hepatic and serum miR-122, HCV replication and hepatic destruction reflects complexities of the virus-host interaction during the acute phase of HCV infection.
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Project description:Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with low-resolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, bla OXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, bla VIM and bla NDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, bla KPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying bla KPC Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread.
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Project description:We report an epidemiologic analysis of 4,210 cases of infection with severe acute respiratory syndrome coronavirus 2 and genetic analysis of 313 new near-complete virus genomes in Panama during March 9-April 16, 2020. Although containment measures reduced R0 and Rt, they did not interrupt virus spread in the country.
| S-EPMC7853578 | biostudies-literature
Project description:Understanding viral dynamics during acute hepatitis C virus (HCV) infection can provide important insights into immunopathogenesis and guide early treatment. The aim of this study was to investigate the dynamics of HCV RNA and alanine transaminase (ALT) levels during recent HCV infection in the Australian Trial in Acute Hepatitis C (ATAHC). ATAHC was a prospective study of the natural history of recently acquired HCV infection. Longitudinal HCV RNA and ALT levels were compared among individuals with persistent infection and spontaneous clearance. Among those with HCV persistence (n = 104) and HCV clearance (n = 30), median HCV RNA (5.2 vs. 4.1 log IU/ml, respectively) and ALT levels (779 vs. 1,765 IU/L, respectively) were high during month two following infection, and then declined during months three and four in both groups. Among those with HCV persistence, median HCV RNA was 2.9 log IU/ml during months four, increased to 5.5 log IU/ml during month five, and remained subsequently relatively stable. Among those with HCV clearance, median HCV RNA was undetectable by month five. Median HCV RNA levels were comparable between individuals with HCV persistence and HCV clearance during month three following infection (3.2 vs. 3.5 log IU/ml, respectively; P = 0.935), but markedly different during month five (5.5 vs. 1.0 log IU/ml, respectively; P < 0.001). In conclusion, dynamics of HCV RNA levels in those with HCV clearance and HCV persistence diverged between months three and five following infection, with the latter time-point being potentially useful for commencing early treatment.
| S-EPMC4276420 | biostudies-literature
Project description:IntroductionDuring pregnancy, immunoglobulin G (IgG) is transferred from the mother to the fetus, providing protection from disease in early infancy. Plasmodium falciparum infections may reduce maternofetal antibody transfer efficiency, but mechanisms remain unclear.MethodsMother-cord paired serum samples collected at delivery from Papua New Guinea (PNG) and the Thailand-Myanmar Border Area (TMBA) were tested for IgG1 and IgG3 to four P. falciparum antigens and measles antigen, as well as total serum IgG. Multivariable linear regression was conducted to assess the association of peripheral P. falciparum infection during pregnancy or placental P. falciparum infection assessed at delivery with maternofetal antibody transfer efficiency. Path analysis assessed the extent to which associations between P. falciparum infection and antibody transfer were mediated by gestational age at delivery or levels of maternal total serum IgG.ResultsMaternofetal antibody transfer efficiency of IgG1 and IgG3 was lower in PNG compared to TMBA (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.88 to 0.09, median of -0.20 log2 units). Placental P. falciparum infections were associated with substantially lower maternofetal antibody transfer efficiency in PNG primigravid women (mean difference in cord antibody levels (controlling for maternal antibody levels) ranged from -0.62 to -0.10, median of -0.36 log2 units), but not multigravid women. The lower antibody transfer efficiency amongst primigravid women with placental infection was only partially mediated by gestational age at delivery (proportion indirect effect ranged from 0% to 18%), whereas no mediation effects of maternal total serum IgG were observed.DiscussionPrimigravid women may be at risk of impaired maternofetal antibody transport with placental P. falciparum infection. Direct effects of P. falciparum on the placenta, rather than earlier gestational age and elevated serum IgG, are likely responsible for the majority of the reduction in maternofetal antibody transfer efficiency with placental infection.
| S-EPMC5640245 | biostudies-literature
Project description:ObjectivesWe aimed to estimate the time-varying transmission dynamics of COVID-19 in China, Wuhan City, and Guangdong province, and compare to that of severe acute respiratory syndrome (SARS).MethodsData on COVID-19 cases in China up to 20 March 2020 was collected from epidemiological investigations or official websites. Data on SARS cases in Guangdong Province, Beijing, and Hong Kong during 2002-3 was also obtained. We estimated the doubling time, basic reproduction number (R0), and time-varying reproduction number (Rt) of COVID-19 and SARS.ResultsAs of 20 March 2020, 80,739 locally acquired COVID-19 cases were identified in mainland China, with most cases reported between 20 January and 29 February 2020. The R0 value of COVID-19 in China and Wuhan was 5.0 and 4.8, respectively, which was greater than the R0 value of SARS in Guangdong (R0 = 2.3), Hong Kong (R0 = 2.3), and Beijing (R0 = 2.6). At the start of the COVID-19 epidemic, the Rt value in China peaked at 8.4 and then declined quickly to below 1.0 in one month. With SARS, the Rt curve saw fluctuations with more than one peak, the highest peak was lower than that for COVID-19.ConclusionsCOVID-19 has much higher transmissibility than SARS, however, a series of prevention and control interventions to suppress the outbreak were effective. Sustained efforts are needed to prevent the rebound of the epidemic in the context of the global pandemic.
| S-EPMC7836966 | biostudies-literature
Project description:The spread of COVID-19 has been greatly impacted by regulatory policies and behavior patterns that vary across counties, states, and countries. Population-level dynamics of COVID-19 can generally be described using a set of ordinary differential equations, but these deterministic equations are insufficient for modeling the observed case rates, which can vary due to local testing and case reporting policies and nonhomogeneous behavior among individuals. To assess the impact of population mobility on the spread of COVID-19, we have developed a novel Bayesian time-varying coefficient state-space model for infectious disease transmission. The foundation of this model is a time-varying coefficient compartment model to recapitulate the dynamics among susceptible, exposed, undetected infectious, detected infectious, undetected removed, hospitalized, detected recovered, and detected deceased individuals. The infectiousness and detection parameters are modeled to vary by time, and the infectiousness component in the model incorporates information on multiple sources of population mobility. Along with this compartment model, a multiplicative process model is introduced to allow for deviation from the deterministic dynamics. We apply this model to observed COVID-19 cases and deaths in several U.S. states and Colorado counties. We find that population mobility measures are highly correlated with transmission rates and can explain complicated temporal variation in infectiousness in these regions. Additionally, the inferred connections between mobility and epidemiological parameters, varying across locations, have revealed the heterogeneous effects of different policies on the dynamics of COVID-19.
| S-EPMC9111166 | biostudies-literature
Project description:Following the 2013-14 outbreak in French Polynesia, the Zika virus (ZIKV) epidemic spread widely to many countries where Aedes Aegypti as the main transmitting vector is endemic. The lack of a second wave of ZIKV infection in most affected regions may suggest that a sufficiently high level of herd immunity was reached during the first wave. We developed an agent-based transmission model to investigate the role of asymptomatic infection on the likelihood of observing a second wave, while accounting for its relative transmissibility. We found that, as the relative transmissibility of asymptomatic infection increases, a second wave is more likely to occur, despite an increase in the attack rate during the first wave. When the reproduction number varies between 1.9 and 2.8 based on estimates for Antioquia, Colombia, the attack rate varies between 4% and 26% for a low (below 10%) effectiveness of interventions in blunting the ZIKV transmission from symptomatic cases to mosquitoes. Moreover, the fraction of cases due to sexual transmission is estimated below 4% of the cumulative incidence. Our analyses underscore the need to quantify the transmissibility of asymptomatic infections, without which the overall attack rates and the level of herd immunity cannot be accurately estimated.
| S-EPMC5517554 | biostudies-literature