Interannual cycles of Hantaan virus outbreaks at the human–animal interface in Central China are controlled by temperature and rainfall

Hantavirus, a rodent-borne zoonotic pathogen, has a global distribution with 200,000 human infections diagnosed annually. In recent decades, repeated outbreaks of hantavirus infections have been reported in Eurasia and America. These outbreaks have led to public concern and an interest in understanding the underlying biological mechanisms. Here, we propose a climate–animal–Hantaan virus (HTNV) infection model to address this issue, using a unique dataset spanning a 54-y period (1960–2013). This dataset comes from Central China, a focal point for natural HTNV infection, and includes both field surveillance and an epidemiological record. We reveal that the 8-y cycle of HTNV outbreaks is driven by the confluence of the cyclic dynamics of striped field mouse (Apodemus agrarius) populations and climate variability, at both seasonal and interannual cycles. Two climatic variables play key roles in the ecology of the HTNV system: temperature and rainfall. These variables account for the dynamics in the host reservoir system and markedly affect both the rate of transmission and the potential risk of outbreaks. Our results suggest that outbreaks of HTNV infection occur only when climatic conditions are favorable for both rodent population growth and virus transmission. These findings improve our understanding of how climate drives the periodic reemergence of zoonotic disease outbreaks over long timescales.

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Threshold dynamics of a general delayed within-host viral infection model with humoral immunity and two modes of virus transmission

Discrete & Continuous Dynamical Systems - B ◽

10.3934/dcdsb.2020259 ◽

2017 ◽

Vol 22 (11) ◽

pp. 0-0

Author(s):

Zhikun She ◽

◽

Xin Jiang ◽

Keyword(s):

Viral Infection ◽

Humoral Immunity ◽

Virus Transmission ◽

Infection Model ◽

Threshold Dynamics ◽

Viral Infection Model

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Ecology and Epidemiology of Eastern Equine Encephalitis Virus in the Northeastern United States: An Historical Perspective

Journal of Medical Entomology ◽

10.1093/jme/tjab077 ◽

2021 ◽

Author(s):

Philip M Armstrong ◽

Theodore G Andreadis

Keyword(s):

United States ◽

Mosquito Species ◽

Virus Transmission ◽

Bird Species ◽

Disease Outbreaks ◽

Encephalitis Virus ◽

Eastern Equine Encephalitis Virus ◽

Northeastern United States ◽

Eastern Equine Encephalitis ◽

Equine Encephalitis Virus

Abstract In the current review, we examine the regional history, ecology, and epidemiology of eastern equine encephalitis virus (EEEV) to investigate the major drivers of disease outbreaks in the northeastern United States. EEEV was first recognized as a public health threat during an outbreak in eastern Massachusetts in 1938, but historical evidence for equine epizootics date back to the 1800s. Since then, sporadic disease outbreaks have reoccurred in the Northeast with increasing frequency and northward expansion of human cases during the last 20 yr. Culiseta melanura (Coquillett) (Diptera: Culicidae) serves as the main enzootic vector that drives EEEV transmission among wild birds, but this mosquito species will occasionally feed on mammals. Several species have been implicated as bridge vectors to horses and humans, with Coquilletstidia perturbans (Walker) as a leading suspect based on its opportunistic feeding behavior, vector competence, and high infection rates during recent disease outbreaks. A diversity of bird species are reservoir competent, exposed to EEEV, and serve as hosts for Cs. melanura, with a few species, including the wood thrush (Hlocichia mustelina) and the American robin (Turdus migratorius), contributing disproportionately to virus transmission based on available evidence. The major factors responsible for the sustained resurgence of EEEV are considered and may be linked to regional landscape and climate changes that support higher mosquito densities and more intense virus transmission.

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Light Modulates Important Pathogenic Determinants and Virulence in Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus ESKAPE Pathogens

Journal of Bacteriology ◽

10.1128/jb.00566-20 ◽

2020 ◽

Author(s):

M. R. Tuttobene ◽

J. F. Pérez ◽

E. Pavesi ◽

B. Perez Mora ◽

D. Biancotti ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Acinetobacter Baumannii ◽

Pathogenic Bacteria ◽

Bacterial Pathogens ◽

General Concept ◽

Infection Model ◽

Type Vi Secretion System ◽

Sense And Respond ◽

Human Infections

Light sensing has been extensively characterized in the human pathogen Acinetobacter baumannii at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that ESKAPE priority pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility and growth under iron deprived conditions are modulated by light in S. aureus. Light also regulates persistence, metabolism and the ability to kill competitors, in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, though the response is not the same in the different species: virulence was enhanced by light in A. baumannii and S. aureus, while in A. nosocomialis and P. aeruginosa it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) are involved in virulence modulation by light in A. baumannii. Overall, this fundamental knowledge highlights the potential use of light to control pathogen's virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration. IMPORTANCE Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease: in the presence of light some of them become more aggressive while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to control infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.

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Shedding and Transmission Modes of Severe Fever With Thrombocytopenia Syndrome Phlebovirus in a Ferret Model

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz309 ◽

2019 ◽

Vol 6 (8) ◽

Cited By ~ 1

Author(s):

Kwang-Min Yu ◽

Hye-Won Jeong ◽

Su-Jin Park ◽

Young-Il Kim ◽

Min-Ah Yu ◽

...

Keyword(s):

Virus Transmission ◽

Body Fluids ◽

Personal Contact ◽

Infection Model ◽

Nasal Discharge ◽

Indirect Contact ◽

Virus Shedding ◽

Transmission Modes ◽

Severe Fever ◽

Urine Specimens

Abstract Background Although human-to-human transmission of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) via direct contact with body fluids has been reported, the role of specific body fluids from SFTSV-infected hosts has not been investigated in detail. Methods To demonstrate the virus transmission kinetics in SFTSV-infected hosts, we adapted the ferret infection model and evaluated the virus shedding periods, virus titers, and transmission modes from various specimens of infected ferrets. Results Large amounts of infectious SFTSV are shed through nasal discharge, saliva, and urine from SFTSV-infected ferrets. Virus could be detected from 2 dpi and persisted until 12 dpi in these specimens, compared with the relatively short virus-shedding period in sera. Further, transmission studies revealed that SFTSV can be transmitted to close direct and indirect contact naïve animals through various mediums, especially through contact with serum and urine. Further, ferrets contacted with human urine specimens from SFTSV-positive patients were successfully infected with SFTSV, suggesting that urine specimens could be a source of SFTSV infection in humans. Conclusions Our results demonstrate that the SFTSV can be shed in various body fluids for more than 12 days and that these specimens could be a source for direct or indirect transmission through close personal contact.

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Development and Characterization of a Sin Nombre Virus Transmission Model in Peromyscus maniculatus

Viruses ◽

10.3390/v11020183 ◽

2019 ◽

Vol 11 (2) ◽

pp. 183 ◽

Cited By ~ 5

Author(s):

Bryce Warner ◽

Derek Stein ◽

Bryan Griffin ◽

Kevin Tierney ◽

Anders Leung ◽

...

Keyword(s):

Peromyscus Maniculatus ◽

Deer Mouse ◽

Virus Transmission ◽

Transmission Model ◽

Deer Mice ◽

Sin Nombre Virus ◽

Infection Model ◽

Main Driver ◽

Heat Shock Responses

In North America, Sin Nombre virus (SNV) is the main cause of hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with a fatality rate of 35–40%. SNV is a zoonotic pathogen carried by deer mice (Peromyscus maniculatus), and few studies have been performed examining its transmission in deer mouse populations. Studying SNV and other hantaviruses can be difficult due to the need to propagate the virus in vivo for subsequent experiments. We show that when compared with standard intramuscular infection, the intraperitoneal infection of deer mice can be as effective in producing SNV stocks with a high viral RNA copy number, and this method of infection provides a more reproducible infection model. Furthermore, the age and sex of the infected deer mice have little effect on viral replication and shedding. We also describe a reliable model of direct experimental SNV transmission. We examined the transmission of SNV between deer mice and found that direct contact between deer mice is the main driver of SNV transmission rather than exposure to contaminated excreta/secreta, which is thought to be the main driver of transmission of the virus to humans. Furthermore, increases in heat shock responses or testosterone levels in SNV-infected deer mice do not increase the replication, shedding, or rate of transmission. Here, we have demonstrated a model for the transmission of SNV between deer mice, the natural rodent reservoir for the virus. The use of this model will have important implications for further examining SNV transmission and in developing strategies for the prevention of SNV infection in deer mouse populations.

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Sudden emergence of human infections with H7N9 avian influenza A virus in Hubei province, central China

Scientific Reports ◽

10.1038/s41598-018-20988-9 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 3

Author(s):

Jiafa Liu ◽

Junqiang Xu ◽

Linlin Liu ◽

Xiaoman Wei ◽

Yi Song ◽

...

Keyword(s):

Avian Influenza ◽

Influenza A Virus ◽

Influenza A ◽

Hubei Province ◽

Central China ◽

Avian Influenza A Virus ◽

Human Infections

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A note on climate in relation to facial eczema outbreaks in sheep in East Gippsland from 1955 to 1964

Australian Journal of Experimental Agriculture ◽

10.1071/ea9650268 ◽

1965 ◽

Vol 5 (18) ◽

pp. 268

Author(s):

E Fisher ◽

AW Kellock ◽

DE Hore ◽

R Sinnott

Keyword(s):

Air Temperature ◽

Climatic Factors ◽

Disease Outbreaks ◽

Climatic Conditions ◽

Factors Associated ◽

Facial Eczema ◽

Minimum Air Temperature

Facial eczema outbreaks of unprecedented severity occurred in Gippsland during 1956 and 1959. With the object of defining the climatic factors associated with disease-outbreaks of this nature, the minimum air-temperature and rainfall recordings made at the R.A.A.F. base, East Sale, from 1955 to 1964 have been noted and critically analysed. The climatic conditions which appear to be necessary for the development of P. chartarum in amounts sufficient to cause facial eczema of sheep In epidemic proportions, are defined for non-irrigated areas.

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Carvacrol ameliorates acute campylobacteriosis in a clinical murine infection model

Gut Pathogens ◽

10.1186/s13099-019-0343-4 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

Soraya Mousavi ◽

Anna-Maria Schmidt ◽

Ulrike Escher ◽

Sophie Kittler ◽

Corinna Kehrenberg ◽

...

Keyword(s):

Intestinal Tract ◽

Farm Animals ◽

Infection Model ◽

Potential Candidate ◽

Disease Symptoms ◽

Ifn Γ ◽

Human Infections ◽

Candidate Molecule ◽

Human Campylobacteriosis ◽

Post Infectious

Abstract Background The prevalence of human infections with the zoonotic pathogen Campylobacter jejuni is rising worldwide. Therefore, the identification of compounds with potent anti-pathogenic and anti-inflammatory properties for future therapeutic and/or preventive application to combat campylobacteriosis is of importance for global health. Results of recent studies suggested carvacrol (4-isopropyl-2-methylphenol) as potential candidate molecule for the treatment of campylobacteriosis in humans and for the prevention of Campylobacter colonization in farm animals. Results To address this in a clinical murine infection model of acute campylobacteriosis, secondary abiotic IL-10−/− mice were subjected to synthetic carvacrol via the drinking water starting 4 days before peroral C. jejuni challenge. Whereas at day 6 post-infection placebo treated mice suffered from acute enterocolitis, mice from the carvacrol cohort not only harbored two log orders of magnitude lower pathogen loads in their intestines, but also displayed significantly reduced disease symptoms. Alleviated campylobacteriosis following carvacrol application was accompanied by less distinct intestinal apoptosis and pro-inflammatory immune responses as well as by higher numbers of proliferating colonic epithelial cells. Remarkably, the inflammation-ameliorating effects of carvacrol treatment were not restricted to the intestinal tract, but could also be observed in extra-intestinal organs such as liver, kidneys and lungs and, strikingly, systemically as indicated by lower IFN-γ, TNF, MCP-1 and IL-6 serum concentrations in carvacrol versus placebo treated mice. Furthermore, carvacrol treatment was associated with less frequent translocation of viable C. jejuni originating from the intestines to extra-intestinal compartments. Conclusion The lowered C. jejuni loads and alleviated symptoms observed in the here applied clinical murine model for human campylobacteriosis highlight the application of carvacrol as a promising novel option for both, the treatment of campylobacteriosis and hence, for prevention of post-infectious sequelae in humans, and for the reduction of C. jejuni colonization in the intestines of vertebrate lifestock animals.

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Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacks activity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2014441117 ◽

2020 ◽

Vol 117 (43) ◽

pp. 26955-26965 ◽

Cited By ~ 11

Author(s):

Suzanne J. F. Kaptein ◽

Sofie Jacobs ◽

Lana Langendries ◽

Laura Seldeslachts ◽

Sebastiaan ter Horst ◽

...

Keyword(s):

Antiviral Drug ◽

Virus Transmission ◽

Small Animal ◽

Antiviral Effect ◽

Viral Disease ◽

Scientific Basis ◽

Infection Model ◽

High Dose ◽

High Doses

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2−infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.

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