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.

Is the delay in diagnosis of pulmonary tuberculosis related to exposure to fluoroquinolones or any antibiotic?

BACKGROUND: Delays in diagnosis of tuberculosis (TB) have been associated with previous use of antibiotics, and in particular fluoroquinolones (FQ), for suspected pulmonary infections. METHODS: We conducted a population-based cohort study with 2232 patients who had active TB between 1997 and 2006 (records obtained from the British Columbia Linked Health Databases). Patients with a record of an initial health care contact preceding the diagnosis of TB were identified for inclusion. Health care delay was defined as the time between initial health care contact and the initiation of anti-tuberculosis medication, and was compared between patients prescribed antibiotics and those not exposed to any antibiotics. RESULTS: A total of 1544 patients were included. After adjusting for covariates, average health care delay for patients exposed to antibiotics was found to be significantly greater, by a factor of 2.10 (95%CI 1.80-2.44), with a median delay of 41 days in the antibiotic group compared to 14 days in the non-antibiotic group. Sex, age, foreign-born status and socio-economic status were non-significant factors. Health care delay increased with the number of antibiotic courses received, but not with the type of antibiotic. CONCLUSIONS: Previous treatment with any antibiotic, and not only a FQ, is associated with a delay in TB diagnosis.

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.

Pulmonary actinomycosis complicating infliximab therapy for Crohn's disease.

The use of anti-tumour necrosis factor (TNF) agents has expanded significantly over the past few years, particularly for rheumatological diseases and Crohn's disease. A number of associated opportunistic infections have been observed as a result of suppression of T cell-mediated immunity, the most frequent being tuberculosis. We report the first case of pulmonary actinomycosis in a patient receiving regular infusions of infliximab, an anti-TNF agent, for Crohn's disease.

Computer-generated dot maps as an epidemiologic tool: investigating an outbreak of toxoplasmosis.

We used computer-generated dot maps to examine the spatial distribution of 94 Toxoplasma gondii infections associated with an outbreak in British Columbia, Canada. The incidence among patients served by one water distribution system was 3.52 times that of patients served by other sources. Acute T. gondii infection among 3, 812 pregnant women was associated with the incriminated distribution system.

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.

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.

Detection of Toxoplasma gondii oocysts in drinking water.

The world's largest outbreak of waterborne toxoplasmosis occurred in a municipality in the western Canadian province of British Columbia. When drinking water emerged as a possible source of infection during the outbreak investigation, a laboratory method was needed to attempt detection of the parasite, Toxoplasma gondii. The method developed was based on the current U.S. Environmental Protection Agency method for detection of Cryptosporidium oocysts. Collection of large-volume drinking water samples and cartridge filter processing were unchanged, although identification of Toxoplasma oocysts in the filter retentate was carried out by using a previously described rodent model. Validation of the method developed was tested by using oocysts from a well-characterized Toxoplasma strain.

Multiple cases of acquired toxoplasmosis retinitis presenting in an outbreak.

OBJECTIVE: The purpose of the study was to examine the variability in presentation and outcome of individuals presenting with acquired toxoplasmosis retinitis in the setting of an outbreak of the disease. DESIGN: The study design was a case series. PARTICIPANTS: Twenty-one eyes of 20 patients with equal gender distribution and a mean age of 54 years followed for 38 to 170 weeks (mean 113.7 weeks) were studied. INTERVENTION: Systemic antimicrobials and corticosteroids when indicated were given. MAIN OUTCOME MEASURES: Visual acuity, media inflammation and clarity, resolution of active retinitis, and appearance of recurrence were observed. RESULTS: Fifteen of 21 lesions were active, and 7 of the total number of lesions fell within the macula-peripapillary region. Overall, vision improved with treatment except in cases of macular involvement (3 cases) and persistent vitritis (3 cases). Four recurrences have occurred to date. CONCLUSIONS: This is the largest reported outbreak of acquired toxoplasmosis retinitis occurring within a single outbreak. Twenty-one eyes of 20 patients presented with retinal lesions, and on average, those treated for active retinitis had improvement in vision.

Outbreak of toxoplasmosis associated with municipal drinking water. The BC Toxoplasma Investigation Team.

BACKGROUND: Outbreaks of toxoplasmosis are recognised infrequently. In March, 1995, a sudden increase of serologically diagnosed cases of acute toxoplasmosis was noted in the Greater Victoria area of British Columbia, Canada. Concurrently, but independently, seven cases of acute toxoplasma retinitis were diagnosed against a background of no cases in the previous 5 years. METHODS: Cases were defined by serological testing, clinical presentation, and residence in Greater Victoria. A screening programme for women who were or had been pregnant was started. Geographical mapping of cases, and case-control studies of symptomatic cases and of women enrolled in the screening programme were done. FINDINGS: 100 individuals aged 6 to 83 years met the definition for an acute, outbreak-related case. 94 resided in Greater Victoria and six had visited it; 19 had retinitis, 51 had lymphadenopathy, four others had symptoms consistent with toxoplasmosis, seven had other symptoms, 18 were symptom-free, and one would not provide information. 36 (0.9%) of 3812 screened pregnant and postnatal women were cases. Excess cases were not detected outside Greater Victoria and no conventional source of toxoplasmosis was implicated. Mapping studies of cases and of the screened women, and both case-control studies showed significant associations between acute infection and residence in the distribution system of one reservoir supplying water to Greater Victoria (ORs or RRs: 3.53, 3.05, 8.27, and 5.42, respectively). The epidemic curve appeared bimodal, with peaks in December, 1994, and March, 1995, that were preceded by increased rainfall and turbidity in the implicated reservoir. INTERPRETATION: A municipal water system that uses unfiltered, chloraminated surface water was the likely source of this large community-wide outbreak of toxoplasmosis.

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)

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.

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)

Minocycline compared with doxycycline in the treatment of nongonococcal urethritis and mucopurulent cervicitis.

OBJECTIVE: To compare the efficacy and tolerability of minocycline versus doxycycline in the treatment of nongonococcal urethritis and mucopurulent cervicitis. DESIGN: Randomized, double-blind trial. SETTING: Sexually transmitted disease clinics. PATIENTS: 151 men and 102 women with nongonococcal urethritis, mucopurulent cervicitis or whose sexual partner had either condition or a positive culture for Chlamydia trachomatis. INTERVENTIONS: Minocycline, 100 mg nightly, or doxycycline, 100 mg twice daily, each administered for 7 days. MEASUREMENTS: At each visit (days 14 +/- 3, 28 +/- 5, and 49 +/- 7) patients were questioned regarding symptoms, signs, drug compliance, and sexual contact. Cultures for C. trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis were obtained at each visit. RESULTS: 253 patients were enrolled (133, doxycycline; 120, minocycline). Chlamydia trachomatis was initially isolated from 31% of men and 39% of women. Men with a positive smear had a higher symptom/sign score (P < 0.001) and were more likely to have chlamydia (P = 0.004). Positive endocervical smears were not associated with symptoms or signs (P > 0.2) but correlated with isolation of chlamydia (P < 0.001). One hundred sixty-two patients (64%) completed the study. The proportion with urethritis or cervicitis did not differ by treatment group at any follow-up visit (P > 0.08). Unprotected sexual contact did not affect clinical or microbiological cure rates. Adverse effects occurred more frequently in the doxycycline group (men: 43% versus 26%; P = 0.05; women: 62% versus 35%; P = 0.009). Although the proportion with dizziness did not differ by drug administered (P = 0.1), dizziness was reported more often by women (11% versus 3%). CONCLUSIONS: Minocycline, 100 mg nightly, was as effective as doxycycline, 100 mg twice daily, each given for 7 days in the treatment of nongonococcal urethritis and mucopurulent cervicitis. Vomiting and gastrointestinal upset occurred more frequently in the doxycycline group.

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.

Need for treatment of gonorrhea to be effective against Chlamydia trachomatis.

Men and women with gonorrhea or contact to gonorrhea are frequently co-infected with Chlamydia trachomatis. To assess the importance of using treatment regimens active against both Neisseria gonorrhoeae and C trachomatis, tetracycline 500 mg orally four times daily for five days, with activity against both organisms, was compared with ceftriaxone, 250 mg once intramuscularly, with activity against only N gonorrhoeae. N gonorrhoeae microbiological failure occurred in six of 148 patients (4%) on tetracycline and zero of 85 on ceftriaxone. Microbiological failure for C trachomatis occurred in zero of 27 on tetracycline and 10 of 12 (83%) on ceftriaxone (P<0.001). In addition, 14 others on ceftriaxone had C trachomatis first isolated after treatment. When all types of microbiologialc and clinical failures are included, outcome was significantly better on tetracycline (P<0.001). Optimal treatment of patients with gonorrhea must include regimens with activity against both C trachomatis and N gonorrhoeae.

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)

Comparison of an in vitro method and an in vivo method of Giardia excystation.

An in vitro method and an in vivo method of excystation were compared to determine the most useful method for the retrieval of Giardia duodenalis isolates. Cysts from 11 Giardia strains were used. In vitro excystation produced motile trophozoites in 16 sets, while in vivo excystation produced trophozoites in all of the 21 comparative sets of excystations. Few cultures were lost because of contamination by either method (17% of in vitro-derived trophozoites versus 23% of in vivo-derived trophozoites; P greater than 0.05). Both methods demonstrated comparable isolate retrieval rates (15% of in vitro-derived trophozoites adapting to culture compared with 29% of in vivo-derived trophozoites; P greater than 0.05), although analysis of the strains retrieved showed that two isolates were retrieved from in vitro excystation alone, compared with four from in vivo excystation. Analysis that included results of extra in vivo cultures showed that a total of nine isolates were retrieved by using this type of excystation. Despite the disadvantages of cost and labor, in vivo excystation appears to be more useful than in vitro excystation for isolate retrieval at the present time.

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.