scholarly journals A biosafety level-2 dose-dependent lethal mouse model of spotted fever rickettsiosis: Rickettsia parkeri Atlantic Rainforest-like isolate

2018 ◽  
Author(s):  
Andrés Felipe Londoño ◽  
Nicole L. Mendell ◽  
David H. Walker ◽  
Donald H. Bouyer ◽  
Keyword(s):  
Mouse Model ◽  
Post Infection ◽  
Spotted Fever ◽  
Spotted Fever Group ◽  
Rickettsia Parkeri ◽  
Spotted Fever Group Rickettsia ◽  
Dose Dependent ◽  
Level 2 ◽  
Biosafety Level ◽  
Biosafety Level 2

Background The species of the Rickettsia genus is separated into four groups: the ancestral group, typhus group, transitional group and spotted fever group. Rickettsia parkeri, a spotted fever group Rickettsia, has been reported across the American continents as infecting several tick species and is associated with a relatively mild human disease characterized by eschar formation at the tick feeding site, fever, myalgia and rash. Currently several mouse models that provide a good approach to study the acute lethal disease caused by Rickettsia, but these models can only be performed in an animal biosafety level 3 laboratory. We present an alternative mouse model for acute lethal rickettsial disease, using R. parkeri and C3H/HeN mice, with the advantage that this model can be studied in an animal biosafety level 2 laboratory. Principal findings In the C3H/HeN mouse model, we determined that infection with 1x106 and 1x107 viable R. parkeri Atlantic Rainforest-like isolate produced dose-dependent severity, whereas infection with 1x108 viable bacteria resulted in a lethal illness. The animals became moribund on day five or six post-infection. The lethal disease was characterized by ruffled fur, erythema, labored breathing, decreased activity, and hunched back, which began on day three post-infection (p.i.) and coincided with the peak bacterial loads. Significant splenomegaly (on days three and five p.i.), neutrophilia (on days three and five p.i.), and thrombocytopenia (on days one, three and five p.i.) were observed. Significance The greatest advantage of this inbred mouse model is the ability to investigate immunity and pathogenesis of rickettsiosis with all the tools available at biosafety level 2.

scholarly journals Beyond the IFA: Revisiting the ELISA as a More Sensitive, Objective, and Quantitative Evaluation of Spotted Fever Group Rickettsia Exposure

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 88
Author(s):  
Navatha Alugubelly ◽  
John V. Stokes ◽  
Claire E. Cross ◽  
Anne-Marie L. Ross ◽  
Anna E. Crawford ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Signal To Noise Ratio ◽  
Spotted Fever ◽  
Clinical Signs ◽  
Enzyme Linked Immunosorbent Assay ◽  
Spotted Fever Group ◽  
Rickettsia Parkeri ◽  
Rickettsial Infections ◽  
Spotted Fever Group Rickettsia ◽  
Guinea Pig Model

Based on limited serological studies, at least 10% of the US population has been exposed to spotted fever group Rickettsia (SFGR) species. The immunofluorescence antibody assay (IFA) has been the gold standard for the serodiagnosis of rickettsial infections such as spotted fever rickettsiosis (SFR). However, the IFA is semi-quantitative and subjective, requiring a high level of expertise to interpret it correctly. Here, we developed an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of Rickettsia parkeri infection in the guinea pig. Our ELISA is an objective, quantitative, and high-throughput assay that shows greater sensitivity and resolution in observed titers than the IFA. We methodically optimized relevant parameters in sequence for optimal signal-to-noise ratio and low coefficient of variation% values. We used a guinea pig model as it is a part of our overall research efforts to understand the immunological and clinical response to SFGR species after tick transmission. Guinea pigs are a useful model to study SFR and show clinical signs of SFR, such as fever and eschars. We anticipate that this assay will be easily adapted to other hosts, including humans and other SFGR species.

scholarly journals A biosafety level-2 mouse model for studying betacoronavirus-induced acute lung damage and systemic manifestations

2021 ◽  
Author(s):  
Ana Cláudia dos Santos Pereira Andrade ◽  
Henrique Gabriel Campolina-Silva ◽  
Celso Martins Queiroz-Junior ◽  
Leonardo Camilo de Oliveira ◽  
Larisse de Souza ◽  
...  
Keyword(s):  
Mouse Model ◽  
Respiratory Infection ◽  
Inflammatory Cytokines ◽  
Lung Damage ◽  
Organ Involvement ◽  
Level 2 ◽  
Biosafety Level ◽  
Pro Inflammatory Cytokines ◽  
Biosafety Level 2

The emergence of life-threatening zoonotic diseases caused by betacoronavirus, including the ongoing COVID-19 pandemic, has highlighted the need for developing preclinical models mirroring respiratory and systemic pathophysiological manifestations seen in infected humans. Here, we showed that C57BL/6J wild-type mice intranasally inoculated with the murine betacoronavirus MHV-3 develop a robust inflammatory response leading to acute lung injuries, including alveolar edema, hemorrhage, and fibrin thrombi. Although such histopathological changes seemed to resolve as the infection advanced, they efficiently impaired the respiratory function, as the infected mice displayed restricted lung distention and increased respiratory frequency and ventilation. Following respiratory manifestation, the MHV-3 infection became systemic and a high virus burden could be detected in multiple organs alongside with morphological changes. The systemic manifestation of MHV-3 infection was also marked by a sharp drop in the number of circulating platelets and lymphocytes, besides the augmented concentration of the pro-inflammatory cytokines IL-1β, IL-6, IL-12, IFN-γ, and TNF, thereby mirroring some clinical features observed in moderate and severe cases of COVID-19. Importantly, both respiratory and systemic changes triggered by MHV-3 infection were greatly prevented by blocking TNF signaling, either via genetic or pharmacologic approaches. In line, TNF blockage also diminished the infection-mediated release of pro-inflammatory cytokines and virus replication of human epithelial lung cells infected with SARS-CoV-2. Collectively, results show that MHV-3 respiratory infection leads to a large range of clinical manifestations in mice and may constitute an attractive, lower cost, biosafety level-2 in vivo platform for evaluating the respiratory and multi-organ involvement of betacoronavirus infections. Importance Mouse models have long been used as valuable in vivo platforms to investigate the pathogenesis of viral infections and effective countermeasures. The natural resistance of mice to the novel betacoronavirus SARS-CoV-2, the causative agent of COVID-19, has launched a race towards the characterization of SARS-CoV-2 infection in other animals (e.g. hamsters, cats, ferrets, bats, and monkeys) as well as the adaptation of the mouse model, by either modifying the host or the virus. In the present study, we utilized the natural pathogen of mice MHV as a prototype to model betacoronavirus-induced acute lung injure and multi—organ involvement under biosafety level 2 condition. We showed that C57BL/6J mice intranasally inoculated with MHV-3 develops a severe disease which includes acute lung damage and respiratory distress preceding systemic inflammation and death. Accordingly, the proposed animal model may provide a useful tool for studies regarding betacoronavirus respiratory infection and related diseases.

scholarly journals Seroprevalence of Rickettsia rickettsii and Rickettsia parkeri in dogs during a Brazilian Spotted Fever outbreak in the State of Rio de Janeiro

2018 ◽  
Vol 70 (3) ◽  
pp. 667-674 ◽  
Author(s):  
I.T. Poubel ◽  
N.C. Cunha ◽  
A.B.M. Fonseca ◽  
A. Pinter ◽  
A.H. Fonseca ◽  
...  
Keyword(s):  
Rio De Janeiro ◽  
Spotted Fever ◽  
Immunofluorescence Assay ◽  
Spotted Fever Group ◽  
Ambient Conditions ◽  
Rickettsia Parkeri ◽  
Rickettsia Rickettsii ◽  
Brazilian Spotted Fever ◽  
Spotted Fever Group Rickettsia ◽  
Janeiro State

ABSTRACT The present paper is the first to perform this evaluation in dogs from the cities of Natividade, Porciuncula and Varre-Sai. The aim of this study is to search for Spotted Fever Group Rickettsia in canine sera using indirect immunofluorescence assay and to identify the probable causative agent of sera reactions in animals. Of the 253 sampled canines, 67.59% (171/253) were seroreactive for Rickettsia rickettsii and 11.07% (28/253) for Rickettsia parkeri, both in dilution 1:64. Titration of tested sera against R. rickettsii antigens reached 1:131.072 and, for R. parkeri, 1:4.096. We conclude that dogs are important sentinels for R. rickettsii infection, and can be infected regardless of sex, age, the habit of visiting woodlands or being in direct contact with equines and capybaras. Serological diagnosis has highlighted many dogs infected by R. rickettsii, and ambient conditions, such as the presence of flowing water bodies, was important for the occurrence of Brazilian Spotted Fever in the northwestern of Rio de Janeiro State.

scholarly journals Isolation of Rickettsia parkeri and Identification of a Novel Spotted Fever Group Rickettsia sp. from Gulf Coast Ticks (Amblyomma maculatum) in the United States

2010 ◽  
Vol 76 (9) ◽  
pp. 2689-2696 ◽  
Author(s):  
Christopher D. Paddock ◽  
Pierre-Edouard Fournier ◽  
John W. Sumner ◽  
Jerome Goddard ◽  
Yasmin Elshenawy ◽  
...  
Keyword(s):  
United States ◽  
Gulf Coast ◽  
Spotted Fever ◽  
The United States ◽  
Spotted Fever Group ◽  
The Novel ◽  
Amblyomma Maculatum ◽  
Rickettsia Parkeri ◽  
Gulf Coast Ticks ◽  
Spotted Fever Group Rickettsia

ABSTRACT Until recently, Amblyomma maculatum (the Gulf Coast tick) had garnered little attention compared to other species of human-biting ticks in the United States. A. maculatum is now recognized as the principal vector of Rickettsia parkeri, a pathogenic spotted fever group rickettsia (SFGR) that causes an eschar-associated illness in humans that resembles Rocky Mountain spotted fever. A novel SFGR, distinct from other recognized Rickettsia spp., has also been detected recently in A. maculatum specimens collected in several regions of the southeastern United States. In this study, 198 questing adult Gulf Coast ticks were collected at 4 locations in Florida and Mississippi; 28% of these ticks were infected with R. parkeri, and 2% of these were infected with a novel SFGR. Seventeen isolates of R. parkeri from individual specimens of A. maculatum were cultivated in Vero E6 cells; however, all attempts to isolate the novel SFGR were unsuccessful. Partial genetic characterization of the novel SFGR revealed identity with several recently described, incompletely characterized, and noncultivated SFGR, including “Candidatus Rickettsia andeanae” and Rickettsia sp. Argentina detected in several species of Neotropical ticks from Argentina and Peru. These findings suggest that each of these “novel” rickettsiae represent the same species. This study considerably expanded the number of low-passage, A. maculatum-derived isolates of R. parkeri and characterized a second, sympatric Rickettsia sp. found in Gulf Coast ticks.

Collaborating With Community Scientists Across Arkansas to Update Tick Distributions and Pathogen Prevalence of Spotted Fever Group Rickettsia and Ehrlichia

2021 ◽  
Author(s):  
Ashley P G Dowling ◽  
Sean G Young ◽  
Kelly Loftin
Keyword(s):  
Tick Species ◽  
Spotted Fever ◽  
Dermacentor Variabilis ◽  
Amblyomma Americanum ◽  
Spotted Fever Group ◽  
Primary Role ◽  
Prevalence Rates ◽  
Spotted Fever Group Rickettsia ◽  
Community Science ◽  
Tick Distributions

Abstract Tick-borne diseases (TBD) in humans have dramatically increased over recent years and although the bulk of cases are attributable to Lyme Disease in the Northeastern US, TBDs like spotted fever rickettsiosis and ehrlichiosis heavily impact other parts of the country, namely the mid-south. Understanding tick and pathogen distributions and prevalence traditionally requires active surveillance, which quickly becomes logistically and financially unrealistic as the geographic area of focus increases. We report on a community science effort to survey ticks across Arkansas to obtain updated data on tick distributions and prevalence of human tick-borne disease-causing pathogens in the most commonly encountered ticks. During a 20-mo period, Arkansans submitted 9,002 ticks from 71 of the 75 counties in the state. Amblyomma americanum was the most common tick species received, accounting for 76% of total tick submissions. Nearly 6,000 samples were screened for spotted fever group Rickettsia (SFGR) and Ehrlichia, resulting in general prevalence rates of 37.4 and 5.1%, respectively. In addition, 145 ticks (2.5%) were infected with both SFGR and Ehrlichia. Arkansas Department of Health reported 2,281 spotted fever and 380 ehrlichiosis cases during the same period as our tick collections. Since known SFGR vectors Dermacentor variabilis and Amblyomma maculatum were not the most common ticks submitted, nor did they have the highest prevalence rates of SFGR, it appears that other tick species play the primary role in infecting humans with SFGR. Our investigation demonstrated the utility of community science to efficiently and economically survey ticks and identify vector-borne disease risk in Arkansas.

scholarly journals Comparative growth of spotted fever group Rickettsia spp. strains in Vero cells

2016 ◽  
Vol 111 (8) ◽  
pp. 528-531
Author(s):  
Arannadia Barbosa Silva ◽  
Myrian Morato Duarte ◽  
Vinicius Figueiredo Vizzoni ◽  
Ana Íris de Lima Duré ◽  
Diego Montenegro Lopéz ◽  
...  
Keyword(s):  
Spotted Fever ◽  
Vero Cells ◽  
Spotted Fever Group ◽  
Spotted Fever Group Rickettsia
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