Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large outbreak of epidemic polyarthritis (EPA) caused by Ross River virus (RRV) occurred in New South Wales in the summer of 1983/1984. The total number of cases was unknown, but 1196 cases were confirmed by laboratory tests. Most patients came from the area west of the dividing range, with especially large numbers in the Murrumbidgee irrigation area. Cases were reported from October 1983 to June 1984, with 60% of cases occurring in January and February. The seasonal pattern was similar throughout the state. Men and women were affected in approximately equal numbers, with the highest frequencies in the 30-39 years' age group. Clinical illness was uncommon in young children. Based on a detailed study of 118 patients from Griffith, arthralgia, lethargy, rash and headache were the most common symptoms. The average period of incapacity (defined as inability to resume normal duties) was about six weeks. On this basis, the cost of the epidemic was estimated at about $3 million. There were 257 cases of EPA in the Griffith Shire and it was calculated that approximately 340 RRV infections occurred in the shire. The implication is that, in this outbreak, most RRV infections resulted in clinical illness.
...
PMID:A major outbreak of epidemic polyarthritis in New South Wales during the summer of 1983/1984. 404 44

Barmah Forest virus (BFV) and Ross River virus (RRV) are mosquito-borne viruses with similar vectors and environmental requirements. They cause diseases characterised by arthralgia, arthritis and myalgia, often accompanied by fever and rash. Arthritis is more common and more prominent in RRV disease and rash is more common and florid with BFV infection, although the diseases cannot be reliably distinguished by their clinical symptoms. Diagnosis is based on serological tests and a definite diagnosis of recent infection requires the demonstration of rising titres of IgG. Arthralgia, myalgia and lethargy may continue for at least six months in up to half of patients with RRV, but in only about 10% of patients with BFV. Both diseases are managed symptomatically.
...
PMID:A comparison of the diseases caused by Ross River virus and Barmah Forest virus. 973 14

Ross River virus (RRV) is an indigenous Australian arthropod-borne alphavirus responsible for epidemic polyarthritis (EPA), myalgia, and lethargy in humans. Macrophages and monocytes have been associated with human RRV disease, and previous studies have shown that RRV is capable of infecting macrophages via both a natural virus receptor and by Fc receptor-mediated antibody-dependent enhancement (ADE). Similar to other viruses, such as human immunodeficiency virus and dengue virus, ADE infection results in dramatic RRV growth increases for in vitro macrophage cultures. This study demonstrates that RRV could resist lipopolysaccharide (LPS)-induced antiviral activity in macrophage cultures when infection was via the ADE pathway. Investigation of this infection pathway found that RRV was able to suppress the transcription and translation of key antiviral genes (tumor necrosis factor and inducible nitric oxide synthase) in LPS-stimulated macrophages by disrupting the transcription into mRNA of the genes coding for the associated transcription factors IRF-1 and NF-kappaB. The transcription of non-antiviral control genes was not perturbed by RRV-ADE infection, and de novo protein synthesis also was not significantly affected in RRV-ADE infected cells. The ADE pathway of infection allowed RRV to specifically target antiviral genes in macrophages, resulting in unrestricted virus replication. As ADE has been observed for several virus families and associated with disease and adverse vaccination outcomes, these findings may have broad relevance to viral disease formation and antiviral vaccination strategies.
...
PMID:Specific ablation of antiviral gene expression in macrophages by antibody-dependent enhancement of Ross River virus infection. 1095 37

This report describes the epidemiological and clinical features of an outbreak of 47 cases of laboratory-confirmed Barmah Forest virus disease (BF disease) that occurred in Victoria between January and May 2002. Laboratory-confirmed cases were investigated, and information on travel history and clinical details was collected. Surveillance data from adult mosquito trappings and climatic conditions in the Wellington Shire were also reviewed. The response rate for interviews was 85 per cent (40/47). The most common symptoms reported by cases included arthralgia (95%), lethargy (90%) and maculopapular rash (72.5%). Transmission of BF disease in the Gippsland region was associated with unusually high numbers of Ochlerotatus camptorhynchus mosquitoes. This outbreak was of interest due to the fact that cases of BF disease outnumbered cases of Ross River virus disease (RR disease) in Victoria for the first time since data were available. Similar outbreaks of BF disease, in the absence of RR disease, occurred in Western Australia in 1993 and New South Wales in 1994/1995. Although the majority of BF disease cases reported regular outdoor activity during which they could be exposed to mosquito populations, they infrequently take precautions to limit exposure. Further efforts need to be made to educate people of the importance of using repellents and other personal preventative measures.
...
PMID:An outbreak of Barmah Forest virus disease in Victoria. 1254 34

Ross River virus (RRV) is a mosquito-borne alphavirus indigenous to Australia and the Western Pacific region and is responsible for several thousand cases of human RRV disease (RRVD) per annum. The disease primarily involves polyarthritis/arthralgia, with many patients also presenting with rash, myalgia, fever, and/or lethargy. The symptoms can be debilitating at onset, but they usually resolve within 3-6 months. Recent insights into the RRV-host relationship, associated pathology, and molecular biology of infection have generated a number of potential avenues for improved treatment. Although vaccine development has been proposed, the small market size and potential for antibody-dependent enhancement (ADE) of disease make this approach unattractive. Recent insights into the molecular basis of RRV-ADE and the virus's ability to manipulate host inflammatory and immune responses create potential new opportunities for therapeutic invention. Such interventions should overcome virus-induced dysregulation of protective host responses to promote viral clearance and/or ameliorate inflammatory immunopathology.
...
PMID:Ross River virus: molecular and cellular aspects of disease pathogenesis. 1592 40

Recently the anti-viral effects of prophylactic treatment with the low-molecular-weight heparan sulfate mimetic PG545 in Ross River virus (RRV) infected mice were reported. We further investigated the related, transient pathophysiology of PG545 drug treatment in RRV-infected and mock-infected PG545-treated mice. PG545 treatment resulted in mild lethargy and piloerection, on days after the drug administration. Mice were treated with two or three doses of PG545 within a ten-day period and were subsequently culled at peak disease or at disease resolution. The treatment responses of the spleen and liver were assessed through histology, flow cytometry, gene arrays and serum biochemistry. Microscopy showed an expanded red pulp in the spleen following either two or three treatments with PG545. The red pulp expansion was further demonstrated by the proliferation of megakaryocytes and erythrocyte precursors within the spleen. In addition, flow cytometry and gene array analyses revealed a reduction of lymphocytes within the spleens of PG545-treated mice. Previously unreported, RRV-induced elevations of aspartate aminotransferase (AST) and alanine transaminase (ALT) enzymes and creatinine were also noted in the RRV-infected mice. However, PG545 only reduced AST and ALT levels but not the creatinine levels in infected mice during treatment. Mice treated with three doses of PG545 also showed hepatosplenomegaly and anaemia, which were reversed upon discontinuation of the treatment. In summary, this study demonstrates that dose and frequency related haemopoietic pathophysiology such as hepatosplenomegaly and anaemia, occurred in C57BL/6 mice treated with PG545. However, this effect was reversible once drug administration is terminated.
...
PMID:PG545 treatment reduces RRV-induced elevations of AST, ALT with secondary lymphoid organ alterations in C57BL/6 mice. 3117 Feb 55