The Impact of Prior Season Vaccination on Subsequent Influenza Vaccine Effectiveness to Prevent Influenza-related Hospitalizations Over 4 Influenza Seasons in Canada.

BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.

Evaluation of a Clostridium difficile infection management policy with clinical pharmacy and medical microbiology involvement at a major Canadian teaching hospital.

WHAT IS KNOWN AND OBJECTIVE: Clostridium difficile infection (CDI) represents a spectrum of disease and is a significant concern for healthcare institutions. Our study objective was to assess whether implementation of a regional CDI management policy with Clinical Pharmacy and Medical Microbiology and Infection Control involvement would lead to an improvement in concordance in prescribing practices to an evidence-based CDI disease severity assessment and pharmacological treatment algorithm. METHODS: Conducted at a tertiary care teaching hospital, this two-phase quality assurance study consisted of a baseline retrospective healthcare record review of patients with CDI prior to the implementation of a regional CDI management policy followed by a prospective evaluation post-implementation. RESULTS AND DISCUSSION: One hundred and forty-one CDI episodes in the pre-implementation group were compared to 283 episodes post-implementation. Overall treatment concordance to the CDI treatment algorithm was achieved in 48 of 141 cases (34%) pre-implementation compared with 136 of 283 cases (48·1%) post-implementation (P = 0·01). The median time to treatment with vancomycin was reduced from five days to one day (P < 0·01), with median length of hospital stay decreasing from 30 days to 21 days (P = 0·01) post-implementation. There was no difference in 30-day all-cause mortality. WHAT IS NEW AND CONCLUSION: A comprehensive approach with appropriate stakeholder involvement in the development of clinical pathways, education to healthcare workers and prospective audit with intervention and feedback can ensure patients diagnosed with CDI are optimally managed and prescribed the most appropriate therapy based on CDI disease severity.

Successful methodology for large-scale surveillance of severe events following influenza vaccination in Canada, 2011 and 2012.

In 2011 and 2012, a nationwide Canadian vaccine safety surveillance network rapidly collected safety data from healthcare workers (HCW) during the first weeks of the annual influenza vaccination campaign. This network provided the first available post-marketing safety data on seasonal influenza vaccines with information on background rates as a comparator. In 2012, these data were used to investigate a possible safety concern regarding a particular vaccine. An online questionnaire was provided to participating HCW two weeks before the annual influenza vaccination campaign for controls, and eight days after influenza vaccination for vaccinees. Control and vaccinees were requested to report health events occurring in the seven days prior to receiving the questionnaire. Control data were used to calculate background rates. HCW reporting a severe event were followed-up by telephone within 48 hours of the online report to validate the report and check on their health status. More than 22,000 vaccinated HCW were enrolled and surveyed over two seasons and > 90% reported no severe event following vaccination. Validated severe event rates were similar in vaccinated HCW and unvaccinated HCW (2.2% vs 2.3%; p < 0.70). The questionnaire was accurately completed for most reported symptoms, matched the validated report and was able to detect events of interest. Prior to the safety concern, the implicated vaccine was in use at one centre. Reassuring safety data were provided to public health authorities 48 hours after the vaccine was temporarily suspended. Data from this and similar networks can be used for rapid evaluation of vaccine safety and for safety assessment as required by the European Medicines Agency in 2015.

Validation of the Seegene RV15 multiplex PCR for the detection of influenza A subtypes and influenza B lineages during national influenza surveillance in hospitalized adults.

Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0 % sensitivity, 100 % specificity and 99.7 % accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2 % sensitivity, 100 % specificity and 99.8 % accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.

Dealing with waterborne disease in Canada: challenges in the delivery of safe drinking water.

Protecting the public from waterborne diseases is an environmental health responsibility that every government worldwide must deal with. Canada's recent experience with waterborne outbreaks has brought the effectiveness of its water-monitoring and treatment systems under scrutiny. This paper focuses on microbial waterborne diseases and the shortcomings of drinking-water systems, dividing them into source control, monitoring, treatment, and operation, epidemiologic, and risk communication issues. Whereas some of these issues are often addressed, others, such as risk communication issues, are less frequently included in drinking water-management plans. Lessons can be learned from the Canadian experience, as these issues are applicable worldwide and especially in the developed world.

Etiology of nongonococcal urethritis. Evidence for Chlamydia trachomatis and Ureaplasma urealyticum.

Chlamydia trachomatis, Ureaplasma urealyticum (T-mycoplasma), and Hemophilus vaginalis have previously been considered possible etiological agents in nongonococcal urethritis (NGU). In this study, current C. trachomatis infection was confirmed by culture and (or) micro-immunofluorescence serology in 26 of 69 men experiencing afirst episode of NGU, and 1 of 39 with no urethritis. Serum IgM immunofluorescent antibody to chlamydia was demonstrated in 16 of 20 men with chlamydia culture positive NGU, and 3 of 39 with chlamydia culture negative NG, and none of 34 with no urethritis. 9 of 10 culture positive men with less than or equal to 10 days symptoms developed immunofluorescent antibody seroconversion in paired sera. U. realyticum was isolated significantly more often and in significantly higher concentration from first voided urine from chlamydia-negative cases of NGU than from chlamydia-positive NGU. Ureaplasmacidal antibody titers increased fourfold in six men, four of whom had negative cultures for for unreaplasma. H. vaginalis was isolated from c9 of 33 men with no urethritis and 2 of 69 with NGU. C. trachomatis is susceptible, and U. urealyticum is resistant to sulfonamides. A 10-day course of sulfisoxazole therapy produced improvement in 13 of 13 chlamydia-positive, unreaplasma-negative, and only 14 of 29 chlamydia-negative, unreaplasma-positive NGU cases (P less than 0.002). Thus, culture, serology, and response to therapy support the etiologic role of chlamydia in NGU. Quantitative culture and response to therapy suggest U. unrealyticum may cause many cases of chlamydia-netative NGU.

Drug therapies for sexually transmitted diseases. Clinical and economic considerations.

Sexually transmitted diseases (STDs) are common, and result in immense social and economic costs. In some countries they have a major demographic impact. Because many STDs facilitate the transmission of HIV, the consequences of STDs are further increasing. At the same time, this association between STDs and HIV provides one of the ways in which drug therapy should be very cost effective. The perspective taken in this article is a societal one, and broader issues than those directly related to drug costs and benefits are discussed. However, it is the availability of drugs that has the potential to most quickly and most reliably make a major difference to overall health sector and societal costs as they relate to STDs. For those STDs for which curative therapy is available (particularly Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, and Trichomonas vaginalis) there have been large decreases in prevalence in many parts of the world. In contrast, those STDs for which curative therapy is not available (particularly HIV, genital herpes and genital human papillomavirus infection) have had stable or increasing prevalence. For these latter infections, each new case increases the overall prevalence. Numerous features of STDs make clinical and economic evaluation difficult. These include the sensitive nature of the topic, the changing epidemiology and drug susceptibility of individual STDs, the fact that a large proportion of those infected are asymptomatic, difficulties in making specific diagnoses, the fact that often consequences are recognised late, sexual re-exposure and reinfection, and inadequate data on which to do clinical and economic evaluations. Furthermore, risk of acquiring an STD roughly correlates inversely with socioeconomic status, and countries or places with the highest rates of STDs may have the least ability to deal effectively with their diagnosis and management. Most of the direct and indirect costs are incurred by women, since they experience the vast majority of the complications of STDs. Many of these only become apparent years later, which makes it very hard to attribute costs and benefits to a specific episode of infection, and to its treatment. The late and indirect costs, plus the costs of prevention, are hard to quantify. That the major burden of STDs is in adolescents and young adults, socioeconomically disadvantaged groups and women has important implications, including for pharmacoeconomic studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Effective treatment of urethritis. A practical guide.

Most cases of urethritis can be readily treated using recommended regimens. The most important causes of urethritis are Chlamydia trachomatis and Neisseria gonorrhoeae, and initial treatment is directed at them. Optimal management requires obtaining a thorough sexual history, evaluation for objective clinical and laboratory evidence of infection, antimicrobial therapy directed towards the major aetiologies, and evaluation and treatment of sexual partners. Treatment of gonorrhoea requires a single-dose regimen active against N. gonorrhoeae, plus a regimen active against C. trachomatis and nongonococcal urethritis. The usually recommended treatment for N. gonorrhoeae is a single dose of ceftriaxone 250mg intramuscularly, but there are many alternatives, including oral ones. Only in very restricted geographical areas and under restricted situations are penicillins still reliable against N. gonorrhoeae. Recommended optimal treatment of C. trachomatis or nongonococcal urethritis currently requires 7 days' treatment with a tetracycline. Some guidelines now propose ofloxacin 300 mg orally twice daily for 7 days as an equivalent alternative, and there are very promising data with a single dose therapy with azithromycin, a long-acting macrolide antimicrobial. Using recommended regimens, microbiological failure is infrequent in compliant patients. Recurrent urethritis is, however, frequent. For patients who receive recommended treatment and do well, no follow-up cultures are needed. Patients with persistent or recurrent symptoms require careful re-evaluation of the patient, documentation of urethritis, and retreatment with antimicrobial agents a second time if urethritis is documented by positive cultures or increased numbers of polymorphonuclear leucocytes in urethral secretions.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiology and therapy of Chlamydia trachomatis infections.

Chlamydia trachomatis infections are exceedingly prevalent, and can be associated with significant sequelae. The major infections are urethritis, cervicitis, salpingitis, and ocular infection. Chlamydial genital infections present as syndromes, where C. trachomatis is one of the causes of the syndrome. Because specific laboratory diagnosis of a chlamydial infection is often not available, and even if available does not exclude the concurrent presence of other pathogens, therapy should usually be directed at all the major causes of the syndrome. Thus, although C. trachomatis is readily eradicated by tetracyclines, macrolides, sulphonamides, and rifampicin, for most situations tetracyclines are the drugs of choice. Penicillins have some activity when used in multiple-dose therapy, but are not reliable for eradication of chlamydiae. Aminoglycosides, nitroimidazoles, and the newer cephalosporins have minimal or no useful activity. Seven days of tetracycline hydrochloride 500mg 4 times daily or doxycycline 100mg twice daily are the optimum regimens for uncomplicated urethritis, cervicitis (except in pregnancy), and gonorrhoea. These regimens should be extended to 10 days for epididymitis and salpingitis. Additional antimicrobials should be added to the salpingitis regimen. For chlamydial infection during pregnancy, erythromycin 500mg 4 times daily for 1 week or 250mg 4 times daily for 2 weeks should be utilised. Neonatal infection requires 2 to 3 weeks of systemic treatment with erythromycin. Inclusion conjunctivitis responds well to antimicrobials, but improved sanitation has a greater effect than antimicrobial therapy in the management of trachoma.

Canadian street youth: correlates of sexual risk-taking activity.

The purpose of this study was to develop a national perspective on the sexual activity of street youth in Canada and to determine the correlates of risky sexual behavior according to street youth's link to the street. Five categories of street youth (sex industry workers, heavy drug and/or alcohol users, young offenders, homeless and unemployed) ages 15 to 20 years were recruited in 1988 from 10 Canadian urban centers to participate in a 45-minute structured interview focusing on knowledge and attitudes regarding sexually transmitted diseases (STD)/human immunodeficiency virus, current sexual practices, sexual and STD history, demographic background, alcohol/drug use and relationship with parents and peers. Data from the survey were also compared with findings from more than 15,000 non-street youth adolescents surveyed in the same year with the use of parallel questionnaires. Of 712 street youth surveyed (391 males, mean age 17.3 years; 321 females, mean age 16.8 years), the majority were sexually active (95% males, 93% females) and 22% reported at least one previous STD (16% males, 30% females). The lowest STD rates were in unemployed males (5%) and the highest (68%) in female sex industry workers. STD/human immunodeficiency virus high risk behaviors were frequent with 47% of males and 41% of females having had at least 10 different partners, 73% of males and 75% of females inconsistently using condoms and 22% of males and 24% of females participating in anal intercourse. Even among sex industry workers more than 40% used condoms inconsistently.(ABSTRACT TRUNCATED AT 250 WORDS)

Human papillomavirus infection of the uterine cervix. Tissue sampling and laboratory methods affect correlations between infection rates and dysplasia.

Two common tissue sampling techniques--colposcopic biopsy and cervical scrape--and two common human papillomavirus (HPV) detection techniques--Southern blot and dot blot (SB and ViraPap [VP])--were compared to determine whether differences in these techniques alter correlations between "oncogenic" HPVs and cervical neoplasia. In 87 women with persistently abnormal Papanicolaou (Pap) smears, concurrent biopsy and scrape specimens contained HPV in 21 (24%) and contained no HPV in 26 (30%); 30 scrape specimens (34.5%) tested positive when the biopsy tested negative and 10 (11.5%) scrape specimens tested negative when the biopsy tested positive (overall concordance, 54%). Concordance for the most prevalent HPVs (16/18) was 59%. In carcinoma in situ, HPV was found in biopsy samples significantly more frequently than in scrape specimens: 17 of 23 (75%) biopsy samples versus 9 of 23 (39%) scrape specimens (P = 0.018). Conversely, in mild or no dysplasia, 0 of 42 biopsy samples tested positive for HPV 16/18 compared with 12 of 42 scrape specimens (29%; P = 0.0001). Of 229 specimens analyzed by SB and VP, 43 (19%) tested positive and 148 (65%) tested negative for HPV by both methods (concordance, 84%). Corroborative results indicated that 29 of 35 (83%) VP-positive SB-negative results were truly positive compared with none of three SB-positive VP-negative results. Both the cervical sampling technique and the method for HPV detection can significantly affect statistical correlations between cervical dysplasia and HPV type.

Antibiotics and sexually transmitted diseases.

There have been gratifying decreases in the rates of several major treatable STDs. These decreases show that diligent application of current preventive and management approaches can be effective. These improvements have not necessarily been reflected as great changes for populations at greatest risk, particularly younger women and those in certain geographic locales or in certain ethnic groups. The CDC 1993 STD guidelines provide updated recommendations for treatment, with key innovations, including an indication of the strength of evidence for certain recommendations, expanded discussions of syndromes, and modifications required in treating infection with HIV. There are many areas in which recommendations concerning efficacy are based on insufficient data. In addition to evaluation of new anti-infectives, key areas for future research are issues of compliance and effectiveness, advantages and appropriateness of liberal treatment of core group or selected populations, and impact of treatments for one STD on risk of transmission of others, particularly HIV. Further study is required on the effects of adjunctive treatments of diseases such as PID.

Isoenzyme analysis of human and animal isolates of Giardia duodenalis from British Columbia, Canada.

Isoenzyme patterns of 32 isolates of Giardia duodenalis, obtained from 6 beavers and 11 humans from British Columbia, plus 15 other isolates were evaluated using thin-layer starch-gel electrophoresis. We attempted to use 12 enzymes; 9 gave reproducible and interpretable results. The isoenzyme patterns of the isolates were classified into 12 groups with 17 (53%) of the 32 isolates confined to 1 group. The other 11 groups each comprised only 1 or 2 isolates. There was no obvious correlation between clinical symptoms and isoenzyme patterns. Our findings suggest that beavers, like humans and gerbils are receptive to organisms with many different isoenzyme patterns.

Epidemic and endemic seroprevalence of antibodies to Cryptosporidium and Giardia in residents of three communities with different drinking water supplies.

This study was carried out to compare cryptosporidiosis and giardiasis seroprevalence rates in residents of three communities. Community (Com 1) uses drinking water from deep wells, community 2 (Com 2) uses surface water from a protected watershed, and community 3 (Com 3) uses surface water frequently containing Cryptosporidium oocysts and Giardia cysts. Unfiltered drinking water from each community was collected at the tap and tested for Cryptosporidium oocysts and Giardia cysts during the 12 months in which sera were collected for testing. No oocysts or cysts were detected in the water from the Com 1 deep wells; oocysts and cysts were detected intermittently in the drinking water from the other two communities. A waterborne outbreak of cryptosporidiosis occurred in a municipality adjacent to Com 3 six months into this 12-month study. Sera from residents of each of the communities were collected proportionately by month and by population size. Coded sera were tested for IgG to Cryptosporidium using a previously developed Western blotting method. The presence or absence of bands at 15-17 kD and/or 27 kD was recorded for the 1,944 sera tested. Definite bands at 15-17 kD and/or 27 kD were detected in 981 (50.5%) of the sera. A total of 33.2% of sera from Com 1 (community using deep wells) were positive using the same criteria compared with 53.5% (Com 2) and 52.5% (Com 3) of sera from the two communities using surface drinking water. Both bands (15-17 kD plus 27 kD) were detected in 582 sera (29.9%) from the three communities: 14.1% of sera from Com 1 compared with 32.7% from Com 2 and 31.5% from Com 3. These findings are consistent with a lower risk of exposure to Cryptosporidium from drinking water obtained from deep well sources. However, analysis of results by calendar quarter showed a significant (P < 0.001) increase in the number of Com 3 positive sera (compared with Com 1) following the waterborne outbreak. Without this outbreak-related observation, a significant overall difference in seropositivity would not have been seen. We also observed that in sera from the community affected by the outbreak, the presence on immunoblots of both Cryptosporidium bands appeared to be the best indicator of recent infection. Seroprevalence rates using an ELISA to detect IgG to Giardia were estimated using the same sera. Overall 30.3% (590 of 1,944) of sera were positive by the ELISA. A total of 19.1% of sera from Com 1, 34.7% from Com 2 and 16.0% from Com 3 were seropositive. Rates for both Com 3 and Com 1 did not change significantly over time. In Com 2, rates decreased significantly (P < 0.001) during the last half of the study period (third and fourth calendar quarters). The reasons for the decrease in seroprevalence in Com 2 sera are presently not known. These studies show intriguing associations between seroprevalence, outbreak-related laboratory serologic data, and patterns of parasite contamination of drinking water. Further studies are required to validate the serologic approach to risk assessment of waterborne parasitic infections at a community level.

Molecular epidemiology of cryptosporidiosis outbreaks and transmission in British Columbia, Canada.

Isolates from 25 (13 sporadic and 12 outbreak) cryptosporidiosis cases, 24 of which were from British Columbia, Canada, were characterized using nested polymerase chain reaction amplification of the polymorphic internal transcribed spacer 1 locus. Two predominant Cryptosporidium parvum genotypes were found. Twelve (8 sporadic and 4 outbreak) isolates amplified with the cry7/cry21 primer pair and 12 (5 sporadic and 7 outbreak) isolates amplified with the cry7/cryITS1 primer pair. Multi-locus gene analysis using sequence polymorphisms on 3 other loci, i.e., the thrombospondin-related adhesion protein gene, the dihydrofolate reductase gene, and the 18S rRNA gene on 8 (4 outbreak and 4 sporadic) isolates showed non-random association among the human and animal alleles of the 4 different C. parvum gene loci. Associations between these 2 parasite genotypes and different routes of cryptosporidiosis transmission such as zoonotic, anthroponotic, and waterborne transmission were studied using municipal population and agricultural information, as well as detection of C. parvum oocysts in municipal drinking water specimens of the residential communities of sporadic and outbreak cases.

Approach to men with urethritis and urologic complications of sexually transmitted diseases.

The most important causes of urethritis, and epididymitis in younger men, are C. trachomatis and N. gonorrhoeae. Management of these syndromes requires a thorough sexual history, genital examination, evaluation for objective and laboratory evidence of infection, antimicrobial therapy directed toward the major etiologies, and evaluation and treatment of sexual partners. Treatment of N. gonorrhoeae requires use of a single-dose regimen active against this organism, plus a 7- to 10-day tetracycline regime active against C. trachomatis and nongonococcal urethritis. With recommended regimens, microbiologic failure is infrequent in compliant patients. Recurrent urethritis is frequent, however. The management of patients with persistent or recurrent symptoms requires careful reevaluation of the patient, documentation of urethritis, and re-treatment with antimicrobials if urethritis is documented by positive cultures or increased numbers of polymorphonuclear leukocytes in urethral secretions. Additional treatment beyond this point usually is not indicated, even though a proportion of men will remain symptomatic and some of these will have increased numbers of polymorphonuclear leukocytes in urethral secretions. The most important causes of prostatitis, and epididymitis in older men or men with urethral structural abnormalities, are classical urinary tract pathogens rather than sexually transmitted pathogens. Management of these infections includes documentation of the infection and treatment directed toward the specific pathogen. Men with symptoms of "prostatitis" must be evaluated using both urine and prostatic secretions to document infection and inflammation. The majority of men with such symptoms do not have an infection that can be documented. These men respond poorly to medications. Men with documented chronic bacterial prostatitis require long courses of antimicrobials to effect cure. In some cases, however, the disease is intractable, and chronic suppression with antimicrobials may be necessary.

Nongonococcal urethritis.

Nongonococcal urethritis is a frequent genital infection, in most cases caused by Chlamydia trachomatis or Ureaplasma urealyticum. Diagnosis requires demonstration of urethritis and exclusion of Neisseria gonorrhoeae infection. Preferred treatment is seven days of tetracycline hydrochloride or doxycycline, to both the patient and partners. Physical sequelae are infrequent but include epididymitis and Reiter's syndrome.

Giardia duodenalis: enhanced growth in cell culture.

Growth of Giardia duodenalis in broth and in animals has been studied in considerable detail. In contrast, the kinetics of growth in cell culture have been little evaluated. In this study, in vitro growth of G. duodenalis was evaluated in cell culture, primarily using mouse McCoy cells in vials. The media used were Giardia broth (TYI-G), Trichomonas vaginalis broth (TYI-T), and standard cell culture media (CMGA) alone and in combination (2 parts by volume CMGA to one part of TYI broth). Addition of cell culture enhanced the sensitivity of the systems in detecting low numbers of G. duodenalis. Growth was identified consistently with inocula less than or equal to 10/ml, and often with a calculated 10-1/ml inoculum with CMGA/TYI-T and CMGA/TYI-G with cells, and with TYI-G with and without cells. The 2 preferred systems for sensitivity and growth were CMGA/TYI-G with cells and TYI-G with cells. The pH fell minimally in the growth systems and, if CMGA was in the media, cell monolayers remained intact and viable throughout the experiment. In preliminary experiments, cell cultures did not allow growth of one strain of G. muris. These cell culture systems may be useful for detection of low numbers of non-laboratory adapted trophozoites, and should be useful in evaluating the interaction of G. dudodenalis with cells in culture.

Regional coronary blood flow in ponies.

Regional coronary blood flow was measured by injecting radioactive microspheres (15 mum +/- 5 in diameter) into the left atrium of anesthetized ponies with surgically prepared open thorax before and during occlusion of the coronary arteries. The normal blood flow to the myocardium of the interventricular septum and the left ventricular wall were highest, followed in decreasing order by the right ventricular wall, the interatrial septum, the atrial walls, and the valves. Measurement of transmural blood flow in the normal left ventricle yielded a mean endocardial/epicardial flow ratio of 1.36 in the free wall. The left ventricular flow ratio was 1.33 in the septal wall. The percentage of the left ventricular myocardium made ischemic during occlusion of the right coronary artery or of the left coronary artery (cranial descending and circumflex arteries) was approximately equal. Blood flow to the ischemic areas of the left ventricle after occlusion of coronary arteries ranged from 3.8 to 20.6% of the normal flow. A disproportionate decrease in flow to the endocardial regions of the left ventricle was also observed in ischemic areas (mean inner/outer left ventricular wall flow ratio was 68.89% of the normal flow ratio).

Etiology of cervicitis and treatment with minocycline.

OBJECTIVE: To evaluate the etiology of cervicitis using the recommended Canadian definition, and to evaluate the efficacy and tolerability of seven days of minocycline treatment, 100 versus 200 mg at bedtime. DESIGN: Randomized double-blind study with initial microbiological evaluation, and intended follow-up through 12 weeks. SETTING: Women attending the major sexually transmitted disease clinic in Vancouver and the major teaching hospital in Winnipeg. POPULATION STUDIED: Women with cervicitis (inclusion criteria were an off-white or yellow colour of cervical mucus when viewed on a white-tipped swab, and a mean of 10 or more polymorphonuclear leukocytes per oil immersion [× 1000] field on Gram stain of cervical mucus). Fourty-four women were enrolled but two were excluded because of contaminated cultures. INTERVENTIONS: Treatment with two identical appearing capsules of 50 mg (100 mg dose) or 100 mg (200 mg dose) of minocycline taken at bedtime with water for seven days. MAIN RESULTS: Of the 42 evaluable women, Chlamydia trachomatis was initially isolated from 19 (45%) and Neisseria gonorrhoeae from four (10%). The study was prematurely terminated because of an unacceptable and significantly higher frequency of adverse reactions on the higher dose regimen of minocycline - severe reactions in one (4%) on 100 mg compared with six (30%) on 200 mg (P=0.05). Major reactions were dizziness, mood alterations and nausea. Clinical parameters, but not numbers of polymorphonuclear leukocytes, improved significantly irrespective of initial microbiology or the regimen received. Cultures became and stayed negative for C trachomatis in seven of eight on minocycline 100 mg and five of six on minocycline 200 mg. Both 'failures' had an intervening negative culture and were re-exposed to untreated sexual partners. CONCLUSIONS: Although not a definitive study in terms of proving efficacy of lower dose regimens, the results are consistent with efficacy and demonstrate the significant advantage of the lower dose regimen in terms of adverse reactions.