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Robert C Brunham

Publications and source records attributed to Robert C Brunham.

At least 37 records · Page 2Linked to original sources
PubMed2004

Aggregate content influences the Th1/Th2 immune response to influenza vaccine: evidence from a mouse model.

During the 2000-2001 season, a newly identified oculo-respiratory syndrome (ORS) was detected across Canada as an adverse effect to one influenza vaccine. The implicated vaccine contained a higher than expected proportion of unsplit and aggregated influenza virions. Clinical and epidemiologic features of ORS were suggestive of type 2-like influences on the immune response. We hypothesized that the implicated vaccine from the 2000-2001 season would induce greater Th2-like polarization relative to the non-implicated vaccine from the same season. Three groups consisting of eight mice each were either immunized with implicated vaccine, immunized with non-implicated vaccine or not immunized. Antigen-specific cellular responses were characterized based on the balance of Th2 (IL-4, IL-5) and Th1 (IFN-gamma) cytokines in vitro. We confirm that vaccine aggregates deviate the immune response to a greater Th2 cytokine pattern with potential implications for vaccine screening, safety, and efficacy.

Animals↗
PubMed2004

Associations among human leukocyte antigen (HLA) class II DQ variants, bacterial sexually transmitted diseases, endometritis, and fertility among women with clinical pelvic inflammatory disease.

BACKGROUND: We investigated associations between HLA class II DQ alleles, chlamydial and gonococcal cervicitis, endometritis, and infertility among women with pelvic inflammatory disease (PID). METHODS: Ninety-two women with clinical signs and symptoms of mild-to-moderate PID, enrolled in the PEACH Study, were evaluated. For all HLA class II DQ alleles with a prevalence of 10% or greater in the population, we assessed demographics, cervical infections, endometrial pathology, and fertility outcomes. RESULTS: Chlamydial cervicitis, gonococcal cervicitis, endometritis, and infertility were all more common among women carrying the DQA *0301 allele after adjustment for race. Endometritis and infertility were somewhat less common (or pregnancy more common) among women carrying the DQA *0501 and DQB *0402 alleles. CONCLUSION: Among women with signs and symptoms of PID, carriage of the DQA *0301, DQA *0501, and DQB *0402 alleles altered the occurrence of lower genital tract infection, upper genital tract inflammation, and infertility.

Adolescent↗
PubMed2004

Novel avian influenza H7N3 strain outbreak, British Columbia.

Genome sequences of chicken (low pathogenic avian influenza [LPAI] and highly pathogenic avian influenza [HPAI]) and human isolates from a 2004 outbreak of H7N3 avian influenza in Canada showed a novel insertion in the HA0 cleavage site of the human and HPAI isolate. This insertion likely occurred by recombination between the hemagglutination and matrix genes in the LPAI virus.

Amino Acid Sequence↗
PubMed2003

Neisseria meningitidis carriage during an outbreak of serogroup C disease.

During 2001, an outbreak of serogroup C meningococcal disease led to immunization of individuals aged 13-29 years in Abbotsford, British Columbia, Canada. This study addresses the distribution of Neisseria meningitidis carriage in this population and the implications of that distribution for the targeting of the immunization campaign. Pharyngeal swabs were obtained at immunization from 2004 people. Colonies were identified and serogrouped using standard agglutination methods and by PCR. Isolates were characterized using pulsed-field gel electrophoresis (PFGE). The prevalence of N. meningitidis carriage was 153 carriers per 2004 subjects (7.6%; 95% confidence interval, 6.5%-8.9%). Only 6 (4%) of the isolates from these carriers were found to be serogroup C by agglutination or PCR testing, and all of these were from individuals within the age group targeted for immunization. Only 1 of these 6 isolates was found to be identical to the outbreak strain by PFGE. The observation that a virulent strain is not circulating widely suggests the possibility of low background immunity in the population at risk and emphasizes the importance of vaccination in controlling epidemic group C meningococcal disease.

Adolescent↗
PubMed2003

The Genome sequence of the SARS-associated coronavirus.

We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.

3' Untranslated Regions↗
PubMed2003

Identification of severe acute respiratory syndrome in Canada.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. METHODS: SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. RESULTS: The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. CONCLUSIONS: SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation.

Adult↗
PubMed2003

Serologic evidence of past infection with Chlamydia trachomatis, in relation to ovarian cancer.

Pelvic inflammatory disease has been inconsistently linked with ovarian cancer. We measured antibodies to Chlamydia trachomatis, to chlamydial heat shock protein (CHSP) 60, and to CHSP10, in 117 women with ovarian cancer and in 171 age- and ethnicity-matched population-based control subjects from Oahu, Hawaii. IgG antibodies to serovar D of chlamydia elementary bodies (EB) and IgG antibodies to CHSP60-1, CHSP60-2, CHSP60-3, and CHSP10 were detected using an ELISA assay. The probability of having ovarian cancer was 90% greater in women with the highest, compared with the lowest (optical density, >or =0.40 vs. <0.10), levels of chlamydia-EB antibodies (P=.05). There was also a monotonic trend (P=.09) in ovarian cancer risk associated with CHSP60-1 but not with CHSP60-2, CHSP60-3, or CHSP10. These data suggest that past or chronic persistent infection with chlamydia may be a risk factor for ovarian cancer.

Adult↗
PubMed2003

Targeted mass treatment for syphilis with oral azithromycin.

From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver. The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000. We aimed to eliminate the syphillis outbreak by treating people at risk of infection. In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city. After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001. Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001<p<0.0044). This rate rebound and the absence of a sustained effect suggest that targeted mass treatment for syphilis, even though feasible, should not be done routinely.

Adolescent↗
PubMed2003

Does antigen-specific cytokine response correlate with the experience of oculorespiratory syndrome after influenza vaccine?

During the 2000-2001 season in Canada, a newly identified oculorespiratory syndrome (ORS) was observed in patients after immunization with inactivated influenza vaccine. ORS was associated with a high proportion of microaggregates of unsplit virions in the implicated vaccine and had clinical features suggesting delayed-onset hypersensitivity. We explore the association between in vitro cytokine balance (type 1 vs. type 2) and clinical ORS after influenza vaccination. We report the balance of interferon (IFN)-gamma, interleukin (IL)-10, IL-5, and IL-13 expression by peripheral blood mononuclear cells (PBMC) among unvaccinated, vaccinated ORS-affected, and vaccinated ORS-unaffected persons after in vitro challenge with implicated and nonimplicated vaccines. Antigen-stimulated PBMC from vaccinated persons produced significantly more IFN-gamma than did those from unvaccinated persons. There was a statistically significant type 2 polarization among unvaccinated compared with vaccinated persons. Although vaccinated ORS-affected individuals had less of a type 1 basis than did vaccinated unaffected individuals, this difference was not statistically significant.

Adult↗
PubMed2003

Immunogenetic correlates for Chlamydia trachomatis-associated tubal infertility.

OBJECTIVE: To understand immunogenetic mechanisms of Chlamydia trachomatis infection and tubal scarring. METHODS: We measured and compared previously significant human leukocyte antigen (HLA) class II DQ alleles, their linked DRB genes, and polymorphisms in selected cytokine genes (tumor necrosis factor alpha-308 promoter; transforming growth factor beta1-10 and -25 codons; interleukin 10-1082, -819, and -592 promoters; interleukin 6-174 promoter; and interferon gamma+874 codon 1) among Kenyan women with confirmed tubal infertility with and without C trachomatis microimmunofluorescence antibody. RESULTS: Two class II alleles, HLA-DR1*1503 and DRB5*0101, were detected less commonly in C trachomatis microimmunofluorescence seropositive women than in C trachomatis microimmunofluorescence seronegative women with infertility (0% versus 20%; odds ratio [OR] 0.05; 95% confidence interval [CI] 0, 0.7, and 6% versus 26%; OR 0.2; 95% CI 0.02, 1.0, respectively). These alleles are commonly linked as a haplotype at the DRB locus. This finding could not be explained through linkage disequilibrium with the other studied HLA or cytokine genes. CONCLUSION: These alleles may lead to an immunologically mediated mechanism of protection against C trachomatis infection and associated tubal damage, or alternatively increase risk for tubal scarring due to another cause.

Adult↗
PubMed2003

Serum antibody response to the heat shock protein 60 of Chlamydia trachomatis in women with developing cervical cancer.

OBJECTIVE: The purpose of this study was to determine whether serum antibody response to the three versions of chlamydial heat shock protein 60 is associated with an increased risk for cervical cancer. STUDY DESIGN: Women with cervical carcinoma were identified by linking the data files of three Nordic serum banks with cancer registries. Overall, 178 women with invasive cervical carcinoma were identified. For each case, the earliest prediagnostic serum sample was chosen, and three matched control subjects who were free of cancer at the time of the case diagnosis were selected randomly. Serum antibodies to the chlamydial heat shock protein 60 were measured by enzyme-linked immunosorbent assay and correlated with the risk of the subsequent development of cervical cancer. RESULTS: Antibodies to chlamydial heat shock protein 60-1 were associated with cervical squamous cell carcinoma among cases with long lag time (>3.5 years; odds ratio, 2.4; 95% CI, 1.1-5.1). Antibodies to chlamydial heat shock protein 60-2 or chlamydial heat shock protein 60-3 were not associated with cervical cancer risk. CONCLUSIONS: The finding that chlamydial heat shock protein 60-1 antibodies are associated with an increased cervical cancer risk suggests that persistent Chlamydia trachomatis infection may contribute to cervical neoplasia.

Antibodies↗
PubMed2003

Impact of mass treatment on syphilis transmission: a mathematical modeling approach.

BACKGROUND: Since 1997 Vancouver (British Columbia, Canada) has experienced an outbreak of heterosexually transmitted infectious syphilis, which prompted a mass treatment campaign in early 2000 in an attempt to control the disease. By 1 year postintervention, syphilis cases had rebounded significantly. We investigate the cause of this postintervention rebound. GOAL: We argue that the observed rebound postintervention may have been the result of the natural dynamics of disease transmission in an open population, in response to the partial application of mass treatment in the sexually active subgroup. STUDY DESIGN: We used a mathematical model that describes the transmission dynamics of syphilis in a population. RESULTS: The observed postintervention rebound is related to the mass treatment intervention. CONCLUSION: Our results suggest that mass treatment may not be an optimal strategy to control the transmission of syphilis if complete coverage of high-frequency transmitters cannot be achieved and if population mobility is relatively high.

Adolescent↗
PubMed2003

Molecular analysis of the multiple GroEL proteins of Chlamydiae.

Genome sequencing revealed that all six chlamydiae genomes contain three groEL-like genes (groEL1, groEL2, and groEL3). Phylogenetic analysis of groEL1, groEL2, and groEL3 indicates that these genes are likely to have been present in chlamydiae since the beginning of the lineage. Comparison of deduced amino acid sequences of the three groEL genes with those of other organisms showed high homology only for groEL1, although comparison of critical amino acid residues that are required for polypeptide binding of the Escherichia coli chaperonin GroEL revealed substantial conservation in all three chlamydial GroELs. This was further supported by three-dimensional structural predictions. All three genes are expressed constitutively throughout the developmental cycle of Chlamydia trachomatis, although groEL1 is expressed at much higher levels than are groEL2 and groEL3. Transcription of groEL1, but not groEL2 and groEL3, was elevated when HeLa cells infected with C. trachomatis were subjected to heat shock. Western blot analysis with polyclonal antibodies raised against recombinant GroEL1, GroEL2, and GroEL3 demonstrated the presence of the three proteins in C. trachomatis elementary bodies, with GroEL1 being present in the largest amount. Only C. trachomatis groEL1 and groES together complemented a temperature-sensitive E. coli groEL mutant. Complementation did not occur with groEL2 or groEL3 alone or together with groES. The role for each of the three GroELs in the chlamydial developmental cycle and in disease pathogenesis requires further study.

Amino Acid Sequence↗
PubMed2003

Levels of antibodies against cytomegalovirus and Chlamydophila pneumoniae are increased in early onset pre-eclampsia.

OBJECTIVE: The origins of pre-eclampsia/eclampsia lie in a mismatch between feto-placental demands and utero-placental supply, a situation that also arises in normotensive intrauterine growth restriction (IUGR). Could reactivated chronic infection be both a trigger for these differential maternal responses to the same underlying pathology and a link between pre-eclampsia and its attendant lifelong risks of atherosclerosis? DESIGN: Nested case-control study. SETTING: Tertiary obstetric centre. POPULATION: Cases of pre-eclampsia, normotensive IUGR and controls. METHODS: A nested case-control study of serum from a population-based bank was performed. Seroprevalence and levels of anti-cytomegalovirus (CMV) and Chlamydophila pneumoniae immunoglobulin G (IgG) were compared (non-parametrically) between women with early onset pre-eclampsia (<34 weeks of gestation, n = 9), late onset pre-eclampsia (> or =34 + 0 weeks of gestation, n = 29), normotensive IUGR (birthweight less than third centile, n = 33) and matched normal pregnancy (n = 113, up to 2 per case). RESULTS: There was a significant difference in both anti-CMV and Chl. pneumoniae antibodies between groups (Kruskal-Wallis test, P < 0.05). Women with early onset pre-eclampsia had higher anti-CMV levels (median: 79, 95% confidence interval [95% CI] = 47, 164) than women with late onset pre-eclampsia (26 [95% CI = 22, 82], P < 0.05), normotensive IUGR (40 [95% CI = 31, 72], P < 0.05) and normal pregnancy (49 [95% CI = 45, 70], P < 0.05). Women with normotensive IUGR had significantly lower anti-Chl. pneumoniae antibodies (0.10 [95% CI = 0.08, 0.38]) than did normal pregnancy controls (0.21 [95% CI = 0.20, 0.28], P <0.05). CONCLUSIONS: The anti-CMV and anti-Chl. pneumoniae antibodies were higher in early onset pre-eclampsia than in late onset pre-eclampsia, normotensive IUGR and normal pregnancy. This may provide a pathophysiological link between pre-eclampsia and the known increased risk for subsequent atherosclerosis.

Adult↗
PubMed2002

GM-CSF transgene-based adjuvant allows the establishment of protective mucosal immunity following vaccination with inactivated Chlamydia trachomatis.

Cellular and humoral immune responses induced following murine Chlamydia trachomatis infection confer almost sterile protection against homologous reinfection. On the other hand, immunization with inactivated organism induces little protective immunity in this model system. The underlying mechanism(s) that determines such divergent outcome remains unclear, but elucidating the mechanism will probably be important for chlamydial vaccine development. One of the distinct differences between the two forms of immunization is that chlamydia replication in epithelial cells causes the secretion of a variety of proinflammatory cytokines and chemokines, such as GM-CSF, that may mobilize and mature dendritic cells and thereby enhance the induction of protective immunity. Using a murine model of C. trachomatis mouse pneumonitis lung infection and intrapulmonary adenoviral GM-CSF transfection, we demonstrate that the expression of GM-CSF in the airway compartment significantly enhanced systemic Th1 cellular and local IgA immune responses following immunization with inactivated organisms. Importantly, immunized mice had significantly reduced growth of chlamydia and exhibited less severe pulmonary inflammation following challenge infection. The site of GM-CSF transfection proved important, since mice immunized with inactivated organisms after GM-CSF gene transfer by the i.p. route exhibited little protection against pulmonary challenge, although i.p. immunization generated significant levels of systemic Th1 immune responses. The obvious difference between i.p. and intrapulmonary immunization was the absence of lung IgA responses following i.p. vaccination. In aggregate, the findings demonstrate that the local cytokine environment is critical to the induction of protective immunity following chlamydial vaccination and that GM-CSF may be a useful adjuvant for a chlamydial vaccine.

Adenoviruses, Human↗
PubMed2002

Association between Mycoplasma genitalium and acute endometritis.

Up to 70% of cases of pelvic inflammatory disease do not have a known cause. We recruited 115 women who had presented to a clinic for sexually transmitted diseases in Nairobi, Kenya with pelvic pain that had persisted for 14 days or less, to look for an association between Mycoplasma genitalium and endometritis. With PCR, we detected M genitalium in the cervix, endometrium, or both in nine (16%) of 58 women with histologically confirmed endometritis and in one (2%) of 57 women without endometritis (p=0.02). Our results suggest that infection with M genitalium is strongly associated with acute endometritis in this population.

Acute Disease↗