Antibody reactivity to the transmembrane protein of the caprine arthritis encephalitis virus correlates with severity of arthritis: No evidence for the involvement of epitope mimicry

Serum and synovial antibody reactivities of caprine arthritis encephalitis virus (CAEV) infected goats were assessed by Western blotting against purified CAEV antigen and the greatest intensity of reactivity in the serum of arthritic goats was to the gp45 transmembrane protein (TM). The extracytoplasmic domain of the TM gene was cloned into a pGEX vector and expressed in Escherichia coil as a glutathione S transferase fusion protein (GST-TM). This clone was found to be 90.5 and 89.2% homologous to published sequences of CAEV TM gene. Serum of 16 goats naturally infected with CAEV were examined by Western blotting for reactivity to the fusion protein. Antibody reactivity to the GST-TM correlated with clinically detectable arthritis (R = 0.642, P ≤ 0.007). The hypothesis that the immune response to the envelope proteins of the CAEV contributes to the severity of arthritis in goats naturally infected with CAEV via epitope mimicry was tested. Antibodies from 5 CAEV infected goats were affinity purified against the GST-TM fusion protein and tested for cross-reactivity with a series of goat synovial extracts and proteogylcans. No serum antibody response or cross-reactivity of affinity purified antibodies could be detected. Peptides of the CAEV SU that were predicted to be linear epitopes and a similar heat shock protein 83 (HSP) peptide identified by database searching, were synthesized and tested for reactivity in CAEV goats using ELISA, in vitro lymphocyte proliferation and delayed type hypersensitivity (DTH) assays. Peripheral blood lymphocytes from 10 of 17 goats with long term natural CAEV infections proliferated in vitro in response to CAEV and in vivo 3 of 7 CAEV infected goats had a DTH reaction to CAEV antigen. However, none of the peptides elicited significant cell mediated immune responses from CAEV infected goats. No antibody reactivity to the SU peptides or HSP peptide was found. We observed that the antibody reactivity to the CAEV TM protein associated with severity of arthritis however epitope mimicry by the envelope proteins of CAEV is unlikely to be involved.

Experimental Infection of Culex Annulirostris, Culex Gelidus, and Aedes Vigilax With a Yellow Fever/Japanese Encephalitis Virus Vaccine Chimera (Chimerivax TM-JE)

Australian mosquitoes from which Japanese encephalitis virus (JEV) has been recovered (Culex annulirostris, Culex gelidus, and Aedes vigilax) were assessed for their ability to be infected with the ChimeriVax-JE vaccine, with yellow fever vaccine virus 17D (YF 17D) from which the backbone of ChimeriVax-JE vaccine is derived and with JEV-Nakayama. None of the mosquitoes became infected after being fed orally with 6.1 log(10) plaque-forming units (PFU)/mL of ChimeriVax-JE vaccine, which is greater than the peak viremia in vaccinees (mean peak viremia = 4.8 PFU/mL, range = 0-30 PFU/mL of 0.9 days mean duration, range = 0-11 days). Some members of all three species of mosquito became infected when fed on JEV-Nakayama, but only Ae. vigilax was infected when fed on YF 17D. The results suggest that none of these three species of mosquito are likely to set up secondary cycles of transmission of ChimeriVax-JE in Australia after feeding on a viremic vaccinee.

Do walking and leisure-time physical activity protect against arthritis in older women?

Objective: To examine the prospective dose–response relationships between both leisure-time physical activity (LTPA) and walking with self-reported arthritis in older women. Design, setting and participants: Data came from women aged 73–78 years who completed mailed surveys in 1999, 2002 and 2005 for the Australian Longitudinal Study on Women’s Health. Women reported their weekly minutes of walking and moderate to vigorous physical activities. They also reported on whether they had been diagnosed with, or treated for, arthritis since the previous survey. General estimating equation analyses were performed to examine the longitudinal relationship between LTPA and arthritis and, for women who reported walking as their only physical activity, the longitudinal relationship between walking and arthritis. Women who reported arthritis or a limited ability to walk in 1999 were excluded, resulting in data from 3613 women eligible for inclusion in these analyses. Main results: ORs for self-reported arthritis were lowest for women who reported “moderate” levels of LTPA (OR 0.78; 95% CI 0.67 to 0.92), equivalent to 75 to <150 minutes of moderate-intensity LTPA per week. Slightly higher odds ratios were found for women who reported “high” (OR 0.81; 95% CI 0.69 to 0.95) or “very high” (OR 0.84; 95% CI 0.72 to 0.98) LTPA levels, indicating no further benefit from increased activity. For women whose only activity was walking, an inverse dose–response relationship between walking and arthritis was seen. Conclusions: The results support an inverse association between both LTPA and walking with self-reported arthritis over 6 years in older women who are able to walk.

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Background: Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As the biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Objectives/methods: Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. Results: There is no clear cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis, but it does cause adverse effects. Conclusion: It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

Long term immunity to live attenuated Japanese encephalitis chimeric virus vaccine : randomized, double-blind, 5-year phase II study in healthy adults.

In a randomized, double-blind study, 202 healthy adults were randomized to receive a live, attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and placebo 28 days apart in a cross-over design. A subgroup of 98 volunteers received a JE-CV booster at month 6. Safety, immunogenicity, and persistence of antibodies to month 60 were evaluated. There were no unexpected adverse events (AEs) and the incidence of AEs between JE-CV and placebo were similar. There were three serious adverse events (SAE) and no deaths. A moderately severe case of acute viral illness commencing 39 days after placebo administration was the only SAE considered possibly related to immunization. 99% of vaccine recipients achieved a seroprotective antibody titer ≥ 10 to JE-CV 28 days following the single dose of JE-CV, and 97% were seroprotected at month 6. Kaplan Meier analysis showed that after a single dose of JE-CV, 87% of the participants who were seroprotected at month 6 were still protected at month 60. This rate was 96% among those who received a booster immunization at month 6. 95% of subjects developed a neutralizing titer ≥ 10 against at least three of the four strains of a panel of wild-type Japanese encephalitis virus (JEV) strains on day 28 after immunization. At month 60, that proportion was 65% for participants who received a single dose of JE-CV and 75% for the booster group. These results suggest that JE-CV is safe, well tolerated and that a single dose provides long-lasting immunity to wild-type strains

Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine : randomized double-blind phase II evaluation of safety and immunogenicity

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril(®), Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE virus strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

Minimum important difference between patients with rheumatoid arthritis : the patient's perspective

OBJECTIVE: To determine the point at which differences in clinical assessment scores on physical ability, pain and overall condition are sufficiently large to correspond to a subjective perception of a meaningful difference from the perspective of the patient. METHODS: Forty patients with a diagnosis of rheumatoid arthritis participated in an evening of clinical assessment and one-on-one conversations with each other regarding their arthritic condition. The assessments included tender and swollen joint counts, clinician and patient global assessments, participant assessment of pain and the Health Assessment Questionnaire (HAQ) on physical ability. After each conversation, participants rated themselves relative to their conversational partner on physical ability, pain and overall condition. These subjective comparative ratings were compared to the differences of the individual clinical assessments. RESULTS: In total there were 120 conversations. Generally participants judged themselves as less disabled than others. They rated themselves as "somewhat better" than their conversation partner when they had a (mean) 7% better score on the HAQ, 6% less pain, and 9% better global assessment. In contrast, they rated themselves as "somewhat worse" when they had a (mean) 16% worse score on the HAQ, 16% more pain, and 29% worse global assessment. CONCLUSIONS: Patients view clinically important differences in an asymmetric manner. These results can provide guidance in interpreting results and planning clinical trials.

Neighbourhood disadvantage, individual-level socioeconomic position, and self-reported chronic arthritis : a cross-sectional multilevel study

Objective: To examine the association between individual- and neighborhood-level disadvantage and self-reported arthritis. Methods: We used data from a population-based cross-sectional study conducted in 2007 among 10,757 men and women ages 40–65 years, selected from 200 neighborhoods in Brisbane, Queensland, Australia using a stratified 2-stage cluster design. Data were collected using a mail survey (68.5% response). Neighborhood disadvantage was measured using a census-based composite index, and individual disadvantage was measured using self-reported education, household income, and occupation. Arthritis was indicated by self-report. Data were analyzed using multilevel modeling. Results: The overall rate of self-reported arthritis was 23% (95% confidence interval [95% CI] 22–24). After adjustment for sociodemographic factors, arthritis prevalence was greatest for women (odds ratio [OR] 1.5, 95% CI 1.4–1.7) and in those ages 60–65 years (OR 4.4, 95% CI 3.7–5.2), those with a diploma/associate diploma (OR 1.3, 95% CI 1.1–1.6), those who were permanently unable to work (OR 4.0, 95% CI 3.1–5.3), and those with a household income <$25,999 (OR 2.1, 95% CI 1.7–2.6). Independent of individual-level factors, residents of the most disadvantaged neighborhoods were 42% (OR 1.4, 95% CI 1.2–1.7) more likely than those in the least disadvantaged neighborhoods to self-report arthritis. Cross-level interactions between neighborhood disadvantage and education, occupation, and household income were not significant. Conclusion: Arthritis prevalence is greater in more socially disadvantaged neighborhoods. These are the first multilevel data to examine the relationship between individual- and neighborhood-level disadvantage upon arthritis and have important implications for policy, health promotion, and other intervention strategies designed to reduce the rates of arthritis, indicating that intervention efforts may need to focus on both people and places.

A case of Kunjin virus encephalitis in a traveller returning from the Northern Territory

On 6 May 2001, a 67-year-old Australian born, Caucasian male presented to the Emergency Department of the Austin and Repatriation Medical Centre (A&RMC) with a 3 day history of fever, lethargy and confusion. This occurred one week after returning from a trip to the Northern Territory. His previous medical problems included ischaemic heart disease, a repaired abdominal aortic aneurysm, hypertension, hyperlipidaemia and congestive cardiac failure. He smoked 20 cigarettes per day and had a history of heavy alcohol consumption. He had no history of diabetes. His medications were aspirin, frusemide, lisinopril, simvastatin, and a nitroglycerol patch. Fifty years ago, he had an adverse reaction to penicillin with angioedema and an urticarial rash. Four weeks before admission he went on a fishing trip in the Northern Territory. He travelled by road, through outback regions of Victoria, New South Wales, Queensland, the Northern Territory and South Australia, spending time in Daly River, Coolum, Darwin, Dunmarra, Avon Downs, Innaminka and Mataranka. He was away for 3 weeks and camped in tents or outside in a swag throughout the trip. He recalls numerous times where he was exposed to mosquitoes with large numbers of bites at Dunmarra. During the time away, he remained well as did his 5 travelling companions. There was...

Ross River virus arthritis

“Epidemics” of a benign disease causing polyarthralgia and rash were first described in Australia in 1927.63 Following the recovery of the causative agent and the advent of serologic tests able to diagnose Ross River virus infection, epidemic polyarthritis has been recognized as endemic in Australia and has occurred as epidemics in numerous Pacific nations. Approximately 4000 cases of epidemic polyarthritis are reported in Australia each year, with a peak of 7800 cases in 1996. Some confusion has been generated recently by use of the term Ross River fever to describe clinical Ross River virus infections because fever does not develop in more than half of those with clinical disease.59 Additional confusion has been generated by efforts to describe any polyarthritis caused by an Australian arbovirus as epidemic polyarthritis. The term epidemic polyarthritis should be used to describe only clinical disease caused by Ross River virus.