scholarly journals Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: development of high levels of viraemia and demonstration of protective immunity

2011 ◽  
Vol 92 (10) ◽  
pp. 2272-2280 ◽  
Author(s):  
Tsutomu Omatsu ◽  
Meng Ling Moi ◽  
Takanori Hirayama ◽  
Tomohiko Takasaki ◽  
Shinichiro Nakamura ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Secondary Infection ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Callithrix Jacchus ◽  
Lymphoid Organs ◽  
Structural Protein ◽  
Primate Model ◽  
Common Marmosets ◽  
Wide Range

Dengue virus (DENV) causes a wide range of illnesses in humans: dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Animal models that constantly develop high levels of viraemia are required for the development of protective and preventive measures. Common marmosets (Callithrix jacchus) demonstrated high levels of viraemia after inoculation with clinical isolates of four serotypes of DENV; in particular, over 106 genome copies ml−1 after inoculation with DENV-2. Non-structural protein 1 and DENV-specific IgM and IgG antibodies were consistently detected. The DENV-2 genome was detected in lymphoid organs including the lymph nodes, spleen and thymus, and also in non-lymphoid organs. DENV antigen was detected by immunohistochemistry in the liver and spleen from inoculated marmosets. Four marmosets were reinoculated with DENV-2 at 33 weeks after primary inoculation with DENV-2. The DENV-2 genome was not detected in any of these marmosets, indicating protection from a secondary infection. The results indicate that common marmosets are highly sensitive to DENV infection, and suggest that marmosets could be a reliable primate model for the evaluation of candidate vaccines.

Demonstration of marmosets (Callithrix jacchus) as a non-human primate model for secondary dengue virus infection: high levels of viraemia and serotype cross-reactive antibody responses consistent with secondary infection of humans

2014 ◽  
Vol 95 (3) ◽  
pp. 591-600 ◽  
Author(s):  
Meng Ling Moi ◽  
Tomohiko Takasaki ◽  
Tsutomu Omatsu ◽  
Shinichiro Nakamura ◽  
Yuko Katakai ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Primary Infection ◽  
Secondary Infection ◽  
Denv Infection ◽  
Callithrix Jacchus ◽  
Antibody Responses ◽  
Infection Model ◽  
Primate Model ◽  
Bhk Cells ◽  
Denv Serotypes

There are four dengue virus (DENV) serotypes. Primary infection with one does not confer protective immunity against the others. We have reported previously that the marmoset (Callithrix jacchus) is a useful primary DENV infection model. It has been reported that secondary DENV infection with a heterotypic serotype induces viraemia kinetics and antibody responses that differ from those in primary infection. Thus, it is important to determine the utility of the marmoset as a model for secondary DENV infection. Marmosets were infected with heterologous DENV by secondary inoculation, and viraemia kinetics and antibody responses were analysed. The marmosets consistently developed high levels of viraemia after the secondary inoculation with heterologous DENV serotypes. IgM responses were lower compared with primary inoculation responses, whilst IgG responses were rapid and high. Neutralizing activities, which possessed serotype cross-reactive activities, were detected as early as 4 days after inoculation. In addition, infectious viraemia titres were higher when assayed with Fcγ receptor-expressing baby hamster kidney (BHK) cells than when assayed with conventional BHK cells, suggesting the presence of infectious virus–antibody immune complexes. After secondary infection with heterotypic DENV, the marmosets demonstrated viraemia kinetics, IgM and IgG responses, and high levels of serotype cross-reactive neutralizing antibody responses, all of which were consistent with secondary DENV infection in humans. The results indicate the marmoset as a useful animal for studying secondary, as well as primary, DENV infection.

scholarly journals Dengue Immunopathogenesis: A Crosstalk between Host and Viral Factors Leading to Disease: Part I - Dengue Virus Tropism, Host Innate Immune Responses, and Subversion of Antiviral Responses

2020 ◽  
Author(s):  
Henry Puerta-Guardo ◽  
Scott B. Biering ◽  
Eva Harris ◽  
Norma Pavia-Ruz ◽  
Gonzalo Vázquez-Prokopec ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Nonstructural Protein ◽  
Secondary Infection ◽  
Hypovolemic Shock ◽  
Clinical Manifestations ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Vascular Leak ◽  
Dengue Disease

Dengue is the most prevalent emerging mosquito-borne viral disease, affecting more than 40% of the human population worldwide. Many symptomatic dengue virus (DENV) infections result in a relatively benign disease course known as dengue fever (DF). However, a small proportion of patients develop severe clinical manifestations, englobed in two main categories known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Secondary infection with any of the four dengue virus serotypes (DENV1, -2, -3, and -4) is a risk factor to develop severe forms of dengue disease. DSS is primarily characterized by sudden and abrupt endothelial dysfunction, resulting in vascular leak and organ impairment, which may progress to hypovolemic shock and death. Severe DENV disease (DHF/DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the cytokine storm, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. In this chapter that is divided in two parts, we will outline the recent advances in our understanding of DENV pathogenesis, highlighting key viral-host interactions and discussing how these interactions may contribute to DENV immunopathology and the development of vascular leak, a hallmark of severe dengue. Part I will address the general features of the DENV complex, including the virus structure and genome, epidemiology, and clinical outcomes, followed by an updated review of the literature describing the host innate immune strategies as well as the viral mechanisms acting against and in favor of the DENV replication cycle and infection.

scholarly journals Airway hyper-responsiveness in lipopolysaccharide-challenged common marmosets (Callithrix jacchus)

2013 ◽  
Vol 126 (2) ◽  
pp. 155-162 ◽  
Author(s):  
Christoph Curths ◽  
Judy Wichmann ◽  
Sarah Dunker ◽  
Horst Windt ◽  
Heinz-Gerd Hoymann ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Inflammation ◽  
Dynamic Compliance ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Acute Lung Inflammation ◽  
Primate Model ◽  
Common Marmosets ◽  
Safety Testing ◽  
Custom Made

Animal models with a high predictive value for human trials are needed to develop novel human-specific therapeutics for respiratory diseases. The aim of the present study was to examine lung-function parameters in marmoset monkeys (Callithrix jacchus) that can be used to detect pharmacologically or provocation-induced AHR (airway hyper-responsiveness). Therefore a custom-made lung-function device that allows application of defined aerosol doses during measurement was developed. It was hypothesized that LPS (lipopolysaccharide)-challenged marmosets show AHR compared with non-challenged healthy subjects. Invasive plethysmography was performed in 12 anaesthetized orotracheally intubated and spontaneously breathing marmosets. Pulmonary data of RL (lung resistance), Cdyn (dynamic compliance), EF50 (mid-expiratory flow), Poes (oesophageal pressure), MV (minute volume), respiratory frequency (f) and VT (tidal volume) were collected. Measurements were conducted under baseline conditions and under MCh (methacholine)-induced bronchoconstriction. The measurement was repeated with the same group of animals after induction of an acute lung inflammation by intratracheal application of LPS. PDs (provocative doses) of MCh to achieve a certain increase in RL were significantly lower after LPS administration. AHR was demonstrated in the LPS treated compared with the naïve animals. The recorded lung-function data provide ground for pre-clinical efficacy and safety testing of anti-inflammatory substances in the common marmoset, a new translational NHP (non-human primate) model for LPS-induced lung inflammation.

scholarly journals UPDATE MANAGEMENT OF DENGUE COMPLICATION IN PEDIATRIC

2015 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Soegeng Soegijanto
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Clinical Performance ◽  
Kidney Injury ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Liver Involvement ◽  
Dengue Virus Infection ◽  
Important Health ◽  
Grade Iii

Dengue virus infection is one of the important health problems in Indonesia, although the mortality rate has been decreased but many dengue shock syndrome cases is very difficult to be solving handled. It might be due to nature course of dengue virus infection is very difficult to predict of the earlier time of severity occur. THE AIM To get idea to make update management of dengue complication in pediatric. MATERIAL AND METHOD Data were compiled from Dr. Soetomo Hospital Surabaya in 2009. The diagnosis of all cases was based on criteria WHO 1997 and PCR examination in Institute Tropical Disease for identified serotype of dengue virus infection. The unusual cases of dengue virus infection were treated following the new WHO protocol in 2009. RESULT There were only 3 cases with serotype DEN 1, consisted 2 cases had age 1–4 years and 1 had age 5–14 years. 2 cases showed a severe clinical performance as dengue shock syndrome and 1 case showed as unusual case of dengue virus infection. Three report cases of: a. Dengue hemorrhagic fever grade III which liver involvement and had bilateral pleural effusion; b. Dengue hemorrhagic grade III with liver involvement and encephalopathy; c. Dengue hemorrhagic grade III with liver involvement acute kidney injury, myocardial involvement and encephalopathy. All the patients were treated according to new edition WHO protocol and all of the involving organ recovered along with the improvement of the disease. CONCLUSION Update management of dengue complication pediatric should be learned carefully used for helping unusual cases of dengue virus infection.

scholarly journals Obesity as a risk factor for dengue shock syndrome in children

2013 ◽  
Vol 53 (4) ◽  
pp. 187 ◽  
Author(s):  
Maria Mahdalena Tri Widiyati ◽  
Ida Safitri Laksanawati ◽  
Endy Paryanto Prawirohartono
Keyword(s):  
Risk Factor ◽  
Viral Infections ◽  
Infection Type ◽  
Secondary Infection ◽  
Univariate Analysis ◽  
Fluid Management ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Control Group ◽  
Case Group

Background Dengue hemorrhagic fever (DHF) leads to highmorbidity and mortality if not be treated properly and promptly.Obesity may play a role in the progression ofDHF to dengue shocksyndrome (DSS) and could be a prognostic factor.Objective To evaluate childhood obesity as a prognostic factorfor DSS.Methods We reviewed medical records of patients with DHFand DSS admitted to Department of Child Health, Dr. SardjitoHospital, Yogyakarta between June 2008 and February 2011.Subjects were aged less than 18 years and fulfilled WHO criteria(1997) for DHF or DSS. The exclusion criteria were the denguefever, a milder form of disease, or other viral infections. Riskfactors for DSS were analyzed by logistic regression analysis.Results Of342 patients who met the inclusion criteria, there were116 DSS patients (33 .9%) as the case group and 226 DHF patients(66.1%) as the control group. Univariate analysis revealed thatrisk factors for DSS were obesity (OR= 1.88; 95%CI 1.01 to3.5 l) ,secondary infection type (OR=0.82; 95%CI 0.41 to 1.63), plasmaleakage with hematocrit increase> 25% (OR=3.42; 95%CI 2.06to 5.65), platelet count < 20,000/μL (OR= l.95; 95%CI 1.20 to3 .16), and inadequate fluid management from prior hospitalization(OR=9.ll; 95% CI 1.13 to 73.66). By multivariate analysis,plasma leakage with hematocrit increase > 25% was associatedwith DSS (OR=2.5 l; 95%CI 1.12 to 5.59), while obesity was notassociated with DSS (OR= l.03; 95%CI 0.32 to3.3 1).Conclusion Obesity is not a risk factor for DSS, while plasmaleakage with hematocrit increase > 25% is associated with DSS.

scholarly journals Roles for Endothelial Cells in Dengue Virus Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Nadine A. Dalrymple ◽  
Erich R. Mackow
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Capillary Permeability ◽  
Virus Disease ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Dengue Virus Infection ◽  
Barrier Functions ◽  
Dengue Disease ◽  
Primary Fluid

Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC) barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease.

The Common Marmoset (Callithrix jacchus) as a Model in Toxicology

2003 ◽  
Vol 31 (1_suppl) ◽  
pp. 123-127 ◽  
Author(s):  
U. Zühlke ◽  
G. Weinbauer
Keyword(s):  
Animal Model ◽  
Current Knowledge ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Human Reproduction ◽  
Background Information ◽  
Reproductive Toxicology ◽  
Primate Model ◽  
Wide Range ◽  
The Common

The common marmoset, Callithrix jacchus, is the smallest nonhuman primate commonly used in biomedical research. Marmoset characteristics and propensities have enabled them to be used in a wide range of research as a model of human disease, physiology, drug metabolism, general toxicology, and reproductive biology. This paper provides a general overview of the marmoset with special emphasis on the benefits and disadvantages of this species as a model for inclusion in preclinical drug development programmes. In view of its small size in comparison with other nonrodent species marmosets have become of value for toxicology studies with biotechnology products where compound supply is limited. In general toxicology studies, marmosets have been successfully used to meet regulatory endpoints also for specific investigatory purposes. The widespread use of this species has allowed extensive background information to become available and a summary of the most frequently measured parameters are presented. Marmosets apparently represent an interesting animal model for comparative research on primate reproductive physiology. However, several basic aspects of reproductive processes exhibit cardinal discrepancies to those described for macaques and human. Thus, from the viewpoint of reproductive toxicology, the relevance of the marmoset primate model for human reproduction remains unclear to date and further research is obviously needed. Given our current knowledge of marmoset reproductive features, the use of this animal model cannot be recommended for reproductive toxicology assessment.

scholarly journals Common Marmosets (Callithrix jacchus) as a Nonhuman Primate Model To Assess the Virulence of Eastern Equine Encephalitis Virus Strains

2008 ◽  
Vol 82 (18) ◽  
pp. 9035-9042 ◽  
Author(s):  
A. Paige Adams ◽  
Judith F. Aronson ◽  
Suzette D. Tardif ◽  
Jean L. Patterson ◽  
Kathleen M. Brasky ◽  
...  
Keyword(s):  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Encephalitis Virus ◽  
Eastern Equine Encephalitis Virus ◽  
Primate Model ◽  
Common Marmosets ◽  
Eastern Equine Encephalitis ◽  
Equine Encephalitis Virus ◽  
The Brain ◽  
Arboviral Disease

ABSTRACT Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral disease in North America (NA) and is a potential biological weapon. However, genetically and antigenically distinct strains from South America (SA) have seldom been associated with human disease or mortality despite serological evidence of infection. Because mice and other small rodents do not respond differently to the NA versus SA viruses like humans, we tested common marmosets (Callithrix jacchus) by using intranasal infection and monitoring for weight loss, fever, anorexia, depression, and neurologic signs. The NA EEEV-infected animals either died or were euthanized on day 4 or 5 after infection due to anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy and survived. The SA EEEV-infected animals developed peak viremia titers of 2.8 to 3.1 log10 PFU/ml on day 2 or 4 after infection, but there was no detectable viremia in the NA EEEV-infected animals. In contrast, virus was detected in the brain, liver, and muscle of the NA EEEV-infected animals at the time of euthanasia or death. Similar to the brain lesions described for human EEE, the NA EEEV-infected animals developed meningoencephalitis in the cerebral cortex with some perivascular hemorrhages. The findings of this study identify the common marmoset as a useful model of human EEE for testing antiviral drugs and vaccine candidates and highlight their potential for corroborating epidemiological evidence that some, if not all, SA EEEV strains are attenuated for humans.

scholarly journals Serotype Infectivity and Phylogenetic of Dengue Virus cause of Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) in Surabaya- Indonesia

2020 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Fedik Rantam
Keyword(s):  
Phylogenetic Analysis ◽  
Nucleotide Sequence ◽  
Dengue Virus ◽  
Dengue Infection ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Rt Pcr ◽  
Who Criteria ◽  
Plasma Leakage ◽  
Degree Of Severity

Infection with DENV causes a spectrum of clinical disease ranging. The aim of this study is to investigate the infectivity of DENV with degree of severity dengue infection in Surabaya. Dengue infection was established by IgM anti dengue, and two step multiplex RT PCR and Nucleotide sequence. Grading of degree severity infection follow the WHO criteria 2011. DSS cases found 3 from 36 patients caused by DENV 2. The most uninfective was DENV 1, and the most prevalence dengue infection caused  by  DENV  3.  The  infectivity of  dengue  infection shown 16 patients lead to severity with plasma leakage. All of sera patients detecting using multiplex RT-PCR were positive, but it were analyzed using Duo ELISA only 22 serum sera positive IgM and IgG from 36 sera. . The Phylogenetic analysis indicates that the isolates from 2011 to 2012 close related with dengue isolate from 1998 and belong to 2009 to 2020.In this study it indicates that DENV 2 predominantly is the cause of DSS.

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