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 ◽  
...  

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.

2008 ◽  
Vol 82 (18) ◽  
pp. 9035-9042 ◽  
Author(s):  
A. Paige Adams ◽  
Judith F. Aronson ◽  
Suzette D. Tardif ◽  
Jean L. Patterson ◽  
Kathleen M. Brasky ◽  
...  

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.


2002 ◽  
Vol 83 (7) ◽  
pp. 1621-1633 ◽  
Author(s):  
Hal B. Jenson ◽  
Yasmin Ench ◽  
Yanjin Zhang ◽  
Shou-Jiang Gao ◽  
John R. Arrand ◽  
...  

A gammaherpesvirus related to Epstein–Barr virus (EBV; Human herpesvirus 4) infects otherwise healthy common marmosets (Callithrix jacchus). Long-term culture of common marmoset peripheral blood lymphocytes resulted in outgrowth of spontaneously immortalized lymphoblastoid cell lines, primarily of B cell lineage. Electron microscopy of cells and supernatants showed herpesvirus particles. There were high rates of serological cross-reactivity to other herpesviruses (68–86%), but with very low geometric mean antibody titres [1:12 to human herpesvirus 6 and 1:14 to Herpesvirus papio (Cercopithecine herpesvirus 12)]. Sequence analysis of the conserved herpesvirus DNA polymerase gene showed that the virus is a member of the lymphocryptovirus subgroup and is most closely related to a lymphocryptovirus from rhesus macaques and is closely related to EBV and Herpesvirus papio. High seroprevalence (79%, with geometric mean antibody titre of 1:110) among 28 common marmosets from two geographically distinct colonies indicated that the virus is likely present in many common marmosets in captivity. A New World primate harbouring a lymphocryptovirus suggests that this subgroup arose much earlier than previously thought.


2003 ◽  
Vol 31 (1_suppl) ◽  
pp. 123-127 ◽  
Author(s):  
U. Zühlke ◽  
G. Weinbauer

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.


2013 ◽  
Vol 81 (8) ◽  
pp. 2909-2919 ◽  
Author(s):  
Laura E. Via ◽  
Danielle M. Weiner ◽  
Daniel Schimel ◽  
Philana Ling Lin ◽  
Emmanuel Dayao ◽  
...  

ABSTRACTExisting small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains ofMycobacterium tuberculosisof various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, andM. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with variousM. tuberculosisstrain clades.


2017 ◽  
Vol 284 ◽  
pp. 35-46 ◽  
Author(s):  
Noeline W. Prins ◽  
Eric A. Pohlmeyer ◽  
Shubham Debnath ◽  
Ramanamurthy Mylavarapu ◽  
Shijia Geng ◽  
...  

Author(s):  
Michelle Nelson ◽  
Francisco J. Salguero ◽  
Laura Hunter ◽  
Timothy P. Atkins

Common marmosets (Callithrix jacchus) were shown to be susceptible to inhalational infection with Coxiella burnetii, in a dose-dependent manner, producing a disease similar to human Q fever, characterized by a resolving febrile response. Illness was also associated with weight loss, liver enzyme dysfunction, characteristic cellular activation, circulating INF-γ and bacteraemia. Viable C. burnetii was recovered from various tissues during disease and from 75% of the animal’s lungs on 28 days post challenge, when there were no overt clinical features of disease but there was histological evidence of macrophage and lymphocyte infiltration into the lung resulting in granulomatous alveolitis. Taken together, these features of disease progression, physiology and bacterial spread appear to be consistent with human disease and therefore the common marmoset can be considered as a suitable model for studies on the pathogenesis or the development of medical counter measures of inhalational Q fever.


Author(s):  
Eui-Suk JEONG ◽  
Jong-Hyung PARK ◽  
Seung-Hyun RYU ◽  
Soo-Young CHOI ◽  
Kyoung-Sun LEE ◽  
...  

Background: Recently, the use of common marmoset (Callithrix jacchus) has increased in biomedical research as an animal model. This study aimed to test fecal samples to monitor bacterial and parasite infections in common marmoset at the Laboratory Animal Center of Osong Medical Innovation Foundation in Korea. Methods: To monitor bacteria and parasites in common marmoset, we tested 43 fecal samples of 43 common marmosets by culture and parasitological test in 2014. Infection by Chilomastix mesnili was determined by PCR method. Results: We identified nonpathogenic bacteria such as Proteus mirabilis and Escherichia coli in feces of normal common marmosets. Interestingly, C. mesnili was isolated from a healthy common marmoset by fecal centrifugation concentration and PCR. The monkey infected with C. mesnili was treated with metronidazole. After the treatment, C. mesnili were not found in feces using fecal centrifugation concentration and PCR. Conclusion: This is the first case report of C. mesnili infection in common marmoset. Treatment with metronidazole is found to be highly effective in eradicating C. mesnili infection in common marmoset.


2010 ◽  
Vol 59 (9) ◽  
pp. 1107-1113 ◽  
Author(s):  
Michelle Nelson ◽  
Mark S. Lever ◽  
Rachel E. Dean ◽  
Victoria L. Savage ◽  
F. Javier Salguero ◽  
...  

The intracellular Gram-negative pathogen Francisella tularensis is the causative agent of tularaemia and is prevalent in many countries in the northern hemisphere. To determine whether the common marmoset (Callithrix jacchus) would be a suitable non-human primate model of inhalational tularaemia, a pathophysiology study was undertaken. Ten animals were challenged with ∼102 c.f.u. F. tularensis strain SCHU S4 (F. tularensis subsp. tularensis). To look for trends in the infection, pairs of animals were sacrificed at 24 h intervals between 0 and 96 h post-challenge and blood and organs were assessed for bacteriology, pathology and haematological and immunological parameters. The first indication of infection was a raised core temperature at 3 days post-challenge. This coincided with a number of other factors: a rapid increase in the number of bacteria isolated from all organs, more pronounced gross pathology and histopathology, and an increase in the immunological response. As the disease progressed, higher bacterial and cytokine levels were detected. More extensive pathology was observed, with multifocal lesions seen in the lungs, liver and spleen. Disease progression in the common marmoset appears to be consistent with human clinical and pathological features of tularaemia, indicating that this may be a suitable animal model for the investigation of novel medical interventions such as vaccines or therapeutics.


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