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Biomedical subjects

S M Garland

Publications and source records attributed to S M Garland.

At least 19 recordsLinked to original sources

The association of Atopobium vaginae and Gardnerella vaginalis with bacterial vaginosis and recurrence after oral metronidazole therapy.

BACKGROUND: We investigated associations between Atopobium vaginae and bacterial vaginosis (BV) and the role that A. vaginae plays in recurrent BV after oral metronidazole therapy. METHODS: Women with abnormal vaginal discharge or odor were enrolled in a cross-sectional study (n=358); the proportion of those infected with Gardnerella vaginalis and A. vaginae was determined by polymerase chain reaction. Women with BV (Nugent score [NS] 7-10 or 4-6 with > or =3 Amsel criteria; n=139) were treated with oral metronidazole (400 mg twice a day for 7 days) and examined at 1, 3, 6, and 12 months or until they reached an NS of 7-10 and recurrence of A. vaginae and G. vaginalis infection was established. RESULTS: A. vaginae and G. vaginalis were highly sensitive for BV--96% (95% confidence interval [CI], 91%-98%) and 99% (95% CI, 97%-100%), respectively. However, A. vaginalis was more specific for BV (77% [95% CI, 71%-82%]) than was G. vaginalis (35% [95% CI, 29%-42%]). G. vaginalis was detected in 100% and A. vaginae in 75% of women with recurrent BV; higher organism loads were present in women with recurrent BV. A. vaginae was rarely detected without G. vaginalis, and women in whom both organisms were detected had higher rates of recurrent BV (83%) than women infected with G. vaginalis only (38%) (P<.001). CONCLUSIONS: Infection with A. vaginae is more specific for BV than infection with G. vaginalis. The higher recurrence rates in women in whom both A. vaginae and G. vaginalis were detected suggest that A. vaginae makes a significant contribution to BV. However, its etiological role remains unclear.

Actinobacteria↗

Genital warts in children: what do they mean?

Human papillomaviruses (HPVs) are a diverse family of viruses, of which 30-40 genotypes specifically infect the genital tract. Genital HPVs are largely transmitted sexually, with most infections being asymptomatic and transient. In contrast, persistent infection with oncogenic genotypes in a minority is a strong risk factor, for subsequent development of high grade dysplasia, the precursor lesion to cervical neoplasia, which generally occurs after a long latency period. It is unknown whether there is a disease correlate in children chronically infected with oncogenic HPVs. Low risk HPV genotypes 6 and 11 are the primary cause of condylomata acuminata, although in children non-genital genotypes are also found in a proportion, with the mode of transmission being either perinatal, horizontal, or sexual. The finding of asymptomatic HPV DNA in children, and correlation with live virus, infectivity, or disease is unclear. Long term follow up for children with anogenital warts is recommended, although there are no longitudinal studies available to clarify whether they are at risk of developing carcinoma in young adulthood.

Anus Neoplasms↗

Newer approaches to the diagnosis of early onset neonatal sepsis.

Accurate and timely diagnosis of early onset neonatal sepsis remains challenging to the clinician and the laboratory. A test with a rapid turnaround time with 100% sensitivity, rather than high specificity, which allows accurate diagnosis and appropriate antimicrobial treatment or which allows antibiotics to be safely withheld in non-infected infants, is desirable. Many potential markers (acute phase reactants, cell surface markers, cytokines) are not routinely available to the laboratory, and most likely combinations of markers will ensure greater diagnostic accuracy. In the future, molecular biology techniques offer the prospect of rapid identification of both pathogens and antimicrobial resistance markers.

Acute-Phase Reaction↗

An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women.

Our objective was to determine the optimal duration of treatment with imiquimod for external genital warts over 4, 8, 12 or 16 weeks. A total of 120 women with a history of genital warts for a median of 3-6 months and prior alternative treatments in 73% were evaluated for total clearance rates. There was no statistically significant difference in complete clearance rates after 16-week follow-up across treatment groups: four weeks (40.0%), eight weeks (48.4%), 12 weeks (39.3%) and 16 weeks (51.6%). Imiquimod was well tolerated, and in those treated for four weeks there was a lower incidence of local skin reactions such as erythema and erosion, and no incidences of pain. These preliminary results suggest that a four-week treatment course of imiquimod applied thrice weekly for women with external genital warts may provide a reasonable approach with comparable efficacy and compliance, and minimal adverse events, drug costs and clinic visits.

Administration, Topical↗

Evaluation of a point-of-care test, BVBlue, and clinical and laboratory criteria for diagnosis of bacterial vaginosis.

Bacterial vaginosis (BV) remains the most common cause of abnormal vaginal discharge in women of reproductive age and is associated with increased susceptibility to human immunodeficiency virus and sexually transmitted infections and preterm delivery. Present diagnostic methods require access to microscopy and laboratory expertise; however, the majority of women, particularly those in populations with a high prevalence of BV, do not have access to clinical services with on-site microscopy capabilities. We evaluated a point-of-care test for the diagnosis of BV, the BVBlue test, with 288 women attending a sexual health service with symptoms of abnormal vaginal discharge and/or odor. The BVBlue test performed well compared with conventional diagnostic methods for the assessment of women with symptoms suggestive of BV at the bedside and significantly better than other simple tests, such as vaginal pH determination and the amine test, that do not require microscopy. The BVBlue test was sensitive (88%; 95% confidence interval [CI], 81 to 93%) and specific (95%; 95% CI, 91 to 98%) compared to the method of Nugent et al. (R. P. Nugent, M. A. Krohn, and S. L. Hillier, J. Clin. Microbiol. 29:297-301, 1991) and performed well compared with the method of Amsel et al. (R. Amsel, P. A. Totten, C. A. Spiegel, K. C. Chen, D. Eschenbach, and K. K. Holmes, Am. J. Med. 74:14-22, 1983), with a sensitivity of 88% (95% CI, 81 to 93%) and a specificity of 91% (95% CI, 85 to 94%). The BVBlue test is a simple, rapid, and objective test for the diagnosis of BV and has the potential to facilitate prompt diagnosis and appropriate treatment of BV in the absence of microscopy. The majority of women at the greatest risk for the sequelae of BV are not in settings where the conventional diagnostic methods are either practical or possible, and they would greatly benefit from access to rapid and reliable point-of-care tests to improve the diagnosis and management of BV.

Adult↗

Screening injecting drug users for sexually transmitted infections and blood borne viruses using street outreach and self collected sampling.

BACKGROUND: Injecting drug users (IDUs) are a marginalised population, who infrequently access health services for screening for sexually transmitted infections (STIs) and blood borne viruses (BBVs), and are at high risk of these infections. OBJECTIVES: To use street outreach and self collection of samples for STI screening, to establish the prevalence of BBVs and STIs, and to identify risk behaviours among a group of culturally diverse street based IDUs. METHODS: This was a cross sectional study of 314 IDUs in the central business district of Melbourne, Australia, conducted over 3 years (1999-2002). We used street outreach as the recruitment strategy with staff "on foot" in injecting and dealing locations, as well as self collected genital sampling to increase acceptance of screening for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis by polymerase chain reaction (PCR). Individuals were screened for hepatitis A, B, and C, syphilis and HIV, and given the option of a self collected or clinician collected blood sample to increase acceptance of screening for BBVs. RESULTS: Street outreach was highly effective and self directed STI sampling was more acceptable than practitioner directed sampling (76% versus 9% acceptance, p<0.001). There was a high prevalence of hepatitis C (74%, 95% CI 69 to 79), STIs (8% (5 to 13)), and chlamydia (6% (3 to 10)), and past exposure to hepatitis A and B was common. High rates of recent sharing of injecting equipment, unprotected sex and casual sexual partners, together with low levels of awareness of current hepatitis C infection were identified. CONCLUSION: Street outreach and self collected genital samples facilitate screening for STIs and BBVs in IDUs and revealed a high prevalence of infections and risk behaviours.

Adolescent↗

A cluster of culture positive gonococcal infections but with false negative cppB gene based PCR.

OBJECTIVES: To describe the prevalence and characteristics of isolates of Neisseria gonorrhoeae grown from urine samples that produced negative results with nucleic acid amplification assays (NAA) targeting the cppB gene. METHODS: An initial cluster of culture positive, but cppB gene based NAA negative, gonococcal infections was recognised. Urine samples and suspensions of gonococci isolated over 9 months in the Northern Territory of Australia were examined using cppB gene based and other non-cppB gene based NAA. The gonococcal isolates were phenotyped by determining the auxotype/serovar (A/S) class and genotyped by pulsed field gel electrophoresis (PFGE). RESULTS: 14 (9.8%) of 143 gonococci isolated were of A/S class Pro(-/)Brpyut, indistinguishable on PFGE and negative in cppB gene based, but not other, NAA. CONCLUSIONS: This cluster represents a temporal and geographic expansion of a gonococcal subtype lacking the cppB gene with consequent loss of sensitivity of NAA dependent on amplification of this target. Gonococci lacking the cppB gene have in the past been more commonly associated with the PAU-/PCU- auxotype, a gonococcal subtype hitherto infrequently encountered in Australia. NAA based on the cppB gene as a target may produce false positive as well as false negative NAA. This suggests that unless there is continuing comparison with culture to show their utility, cppB gene based NAA should be regarded as suboptimal for use either as a diagnostic or supplemental assay for diagnosis of gonorrhoea, and NAA with alternative amplification targets should be substituted.

Bacterial Outer Membrane Proteins↗

Comparison of conventional testing to polymerase chain reaction in detection of Trichomonas vaginalis in indigenous women living in remote areas.

There are high rates of Trichomonas vaginalis in remote areas of Central Australia. Conventional tests for T. vaginalis have low sensitivity in this setting. Aims of the study were to estimate the prevalence of T. vaginalis, to assess the presence of clinical signs and symptoms, to compare a T. vaginalis polymerase chain reaction (PCR) test with conventional methods of diagnosis, and to compare the PCR from different samples, including self-collected swabs (SCS). Of 205 women recruited, the prevalence of T. vaginalis was 24%. The prevalence of T. vaginalis was higher in women under 25 years (33%), compared with those who were 25-34 years (26%) and those over 35 years (15%, P < 0.05). The sensitivity of T. vaginalis PCR detection from SCS (94%) was not statistically different from a practitioner-collected HVS (96%), but was superior to urine PCR (74%) and conventional methods. After multivariate analysis, those women with high pH were almost three times more likely to be positive for T. vaginalis (odds ratio = 2.71 with 95% confidence interval 1.06-6.93, P = 0.037). Superior assays such as PCR should be a diagnostic option to adequately screen and treat women with T. vaginalis, in order to reduce complications, including the increased risk of HIV transmission.

Adult↗

Prevention of neonatal group B streptococcal disease: progress, challenges and dilemmas.

Significant advances in the prevention of neonatal group B streptococcal (GBS) disease have occurred in the last decade. In Australia, as well as in centres overseas, intrapartum penicillin given to carrier mothers has been shown to unequivocally decrease early onset neonatal GBS sepsis. In choosing which women should receive intrapartum chemoprophylaxis, recent data suggest that screening programmes for the detection of GBS carriage may be more effective than risk-based strategies to prevent early onset neonatal GBS sepsis. Combined vaginal and rectal swabs, collected between 35 and 37 weeks gestation, either by a health care worker or by the patient herself and inoculated onto selective media after enrichment provide the optimum conditions to detect carriage. Increasingly erythromycin and clindamycin resistance is being described overseas, which may influence the choice of antibiotics used in those allergic to penicillin. Widespread antibiotic use, particularly with broad-spectrum agents, may lead to increasing neonatal sepsis with ampicillin resistant organisms. Whilst rates of non-GBS neonatal sepsis are generally stable there is evidence suggesting that Escherichia coli sepsis in premature infants is increasing. Novel vaccination strategies for GBS are being developed that may ultimately provide broader protection for mothers and babies and eliminate the need for intrapartum antibiotics.

Anti-Bacterial Agents↗

Evaluation of real time polymerase chain reaction assays for confirmation of Neisseria gonorrhoeae in clinical samples tested positive in the Roche Cobas Amplicor assay.

OBJECTIVE: Development of a rapid, sensitive, and accurate assay for confirmation of Neisseria gonorrhoeae in clinical samples. METHOD: Two real time polymerase chain reaction (PCR) assays, developed on the LightCycler for amplification of the N gonorrhoeae cppB gene, were utilised for confirmation of this bacterial pathogen in samples positive by the Roche Cobas Amplicor assay. Performance characteristics of the two assays were compared with other commercial nucleic acid amplification assays, including the Abbott LCx and Roche 16S rRNA tests. RESULTS: All related Neisseria as well as other bacterial species tested negative by both cppB gene based assays, whereas 120 N gonorrhoeae clinical isolates from various geographical regions gave in positive results. Both assays had a sensitivity of one copy per reaction. 122 clinical samples positive and another 50 samples negative for N gonorrhoeae by Roche Cobas Amplicor were selected from a specimen pool of more than 3000 women tested previously. Overall, 73 of 122 (59.8%) samples were confirmed as positive. The two real time assays had sensitivities of 99% and 100% and specificities of 98% and 100%, respectively. The 16S and LCx assays produced similar results to the real time assays, indicating a similar sensitivity to and specificity of both real time assays. CONCLUSION: The data from this study highlight the need to confirm N gonorrhoeae positive Cobas Amplicor PCR results as an important part of the testing algorithm of all diagnostic laboratories utilising this assay.

DNA, Bacterial↗

Prevalence of sexually transmitted diseases and human immunodeficiency virus among women attending prenatal services in Apia, Samoa.

There is no routine prenatal screening for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV) in pregnancy in Samoa. Testing for chlamydial infection is not available. To gather information on pregnant women, a prevalence survey was conducted in Apia, Samoa, utilizing two prenatal hospital clinics. Pregnant (n=427) women were tested for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis using polymerase chain reaction (PCR), and for syphilis (n=441) by rapid plasmid reagin (RPR) and HIV (n=441) by enzyme-linked immunosorbent assay (ELISA). Results were: chlamydia 30.9% (132); trichomoniasis 20.8%; gonorrhoea 3.3%; syphilis 0.5%; and HIV 0%. Overall 42.7% had at least 1 STD. Young women aged <25 years were three times more likely to have a STD than older women (odds ratio=3.0, 95% confidence intervals 2.0, 4.5). The lack of inexpensive, reliable field diagnostics remain a barrier to sustainable STD control programmes for pregnant women living in developing countries.

Adolescent↗

Genetic aberrations detected by comparative genomic hybridisation in vulvar cancers.

Squamous cell carcinoma of the vulva is a disease of significant clinical importance, which arises in the presence or absence of human papillomavirus. We used comparative genomic hybridisation to document non-random chromosomal gains and losses within human papillomavirus positive and negative vulvar cancers. Gain of 3q was significantly more common in human papillomavirus-positive cancers compared to human papillomavirus-negative cancers. The smallest area of gain was 3q22-25, a chromosome region which is frequently gained in other human papillomavirus-related cancers. Chromosome 8q was more commonly gained in human papillomavirus-negative compared to human papillomavirus-positive cancers. 8q21 was the smallest region of gain, which has been identified in other, non-human papillomavirus-related cancers. Chromosome arms 3p and 11q were lost in both categories of vulvar cancer. This study has demonstrated chromosome locations important in the development of vulvar squamous cell carcinoma. Additionally, taken together with previous studies of human papillomavirus-positive cancers of other anogenital sites, the data indicate that one or more oncogenes important in the development and progression of human papillomavirus-induced carcinomas are located on 3q. The different genetic changes seen in human papillomavirus-positive and negative vulvar squamous cell carcinomas support the clinicopathological data indicating that these are different cancer types.

Carcinoma, Squamous Cell↗

Molecular epidemiology of coagulase-negative staphylococcal bacteraemia in a newborn intensive care unit.

We isolated 55 coagulase-negative staphylococci (CoNS) over two separate 12-month periods (26 in 1993 and 29 in 1996) from the blood of neonates in a neonatal intensive case unit (NICU) in Melbourne, Australia and compared them by pulse-field gel electrophoresis profile (PFGE), random amplification of polymorphic DNA (RAPD) and antibiogram. The most common species were Staphylococcus epidermidis, S. haemolyticus and S. warneri. The majority of such isolates were resistant to penicillin and to either or both of methicillin and gentamicin. During 1993, there was an increase in the number of CoNS bloodstream infections compared with previous years. S. epidermidis was the most common isolate, with 88% assessed as clinically relevant. Using the three typing systems, we identified one likely epidemic clone of S. epidermidis, the isolates of which were resistant to penicillin, gentamicin and erythromycin and possessed the mecA gene. There was complete correlation between the detection of mecA and the phenotypic expression of resistance when zone diameters in the disc diffusion assay were interpreted according to the latest NCCLS guidelines (1999). Profiles of the remaining 1993 isolates were generally heterogeneous, suggesting independent acquisition with some evidence of cross-infection. The predominant bloodstream isolates in 1996 were heterogeneous multi-resistant strains of S. epidermidis, S. haemolyticus and S. warneri, about half of which were assessed as clinically relevant. These data support the view that CoNS are significant nosocomial pathogens in NICU and that resistant clones may be transmitted between babies. Molecular epidemiological tools are helpful for understanding transmission patterns and sources of infection, and are useful for measuring outcomes of intervention strategies implemented to reduce nosocomial CoNS sepsis. PFGE was found to be more discriminatory than RAPD, but the latter provides results in a more timely manner.

Australia↗