Lymphogranuloma venereum in Quebec: Re-emergence among men who have sex with men.

BACKGROUND: Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis genotypes L1, L2 and L3. This LGV is associated with significant morbidity and increased risk of HIV transmission. While fewer than two cases per year were reported in Quebec before 2005, LGV emerged in 2005-2006 with 69 cases, followed by a period of low incidence (2007-2012), and subsequent re-emergence since 2013. OBJECTIVES: To describe the incidence of LGV in Quebec and the characteristics of the affected population, including demographics and risk factors, clinical manifestations, laboratory tests, treatments and reinfection rates. METHODS: Descriptive data were collected from the notifiable diseases records through the Institut national de santé publique du Québec (INSPQ) infocentre portal. Questionnaires were obtained through the enhanced surveillance system and transmitted anonymously to the Quebec Ministry of Health. In-depth analysis was performed on cases from 2013 to 2016. RESULTS: There were 338 cases of LGV over the four-year period in Quebec. All cases were male, excluding one transsexual. Mean age was 41 years. Most lived in Montréal (81%) and were men who have sex with men (MSM; 99%). The majority (83%) reported four sexual partners or more in the last year, met mostly through the Internet (77%) and in saunas (73%). Frequency of sexual intercourse with out-of-province residents decreased in 2013-2016 (27%) compared with 2005-2012 (38%). History of STIs was frequent: 83% were HIV-infected, 81% reported previous syphilis and 78% previous gonorrhea. Recreational drug use was frequent (57%), reaching 71% in 2016. Most cases were symptomatic, a proportion which decreased in 2016 (68%) compared with 2013-2015 (82%; p=0.006). Clinical presentations included proctitis (86%), lymphadenopathy (13%) and ulcer/papule (12%). Reinfections, mostly within two years of first infection, occurred in 35 individuals (10%).Conclusion: The re-emergence of LGV in Quebec involves an urban subpopulation composed almost exclusively of MSM with STIs, who have a high number of partners and often use drugs.

HPV E6 oncoproteins and nucleic acids in neck lymph node fine needle aspirates and oral samples from patients with oropharyngeal squamous cell carcinoma.

Commercial assays measuring HPV E6 viral oncoproteins, E6/E7 mRNA or DNA were used to test neck lymph node fine needle aspirates (FNA) and oropharyngeal samples (saliva and oral swabs) from 59 Canadian patients with oropharyngeal squamous cell carcinomas (OPSCC). Overall agreements of p16 antigen staining of tumors to FNA tested for OncoE6™, Aptima HPV E6/E7 mRNA and cobas HPV DNA were 81.4% (k 0.53), 94.9% (k 0.83) and 91.1% (k 0.73) respectively. Using HPV presence in a subset of 25 tumors as the comparator, overall agreement was 64.0% (k 0.08) with OncoE6™, 88.0% (k 0.65) with Aptima HPV E6/E7 mRNA and 91.7% (k 0.70) with cobas HPV DNA. HPV testing of oropharyngeal samples yielded lower agreements with tumor markers; 23.7-24.0% (k 0.02), 55.9-68.0% (k 0.24-0.37) and 78.9-86.9% (k 0.49-0.58) in the 3 respective tests. HPV 16 was present in 93.7-100% of the samples tested and showed 100% genotype agreement between FNA and tumors. The high rates for HPV E6 oncoproteins and E6/E7 mRNA suggests most patients were experiencing transcriptionally active HPV-related OPSCC. Results from these commercial assays performed on FNA but not oropharyngeal samples showed moderate to very good agreements with p16 and HPV testing of tumors.

The diagnosis of genital herpes - beyond culture: An evidence-based guide for the utilization of polymerase chain reaction and herpes simplex virus type-specific serology.

Accurate identification of persons with genital herpes is necessary for optimal patient management and prevention of transmission. Because of inherent inaccuracies, clinical diagnosis of genital herpes should be confirmed by laboratory testing for the causative agents herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). Further identification of the HSV type is valuable for counselling on the natural history of infection and risk of transmission. Laboratory methods include antigen detection, culture, polymerase chain reaction (PCR) and conventional and type-specific serology (TSS). PCR has, by far, the greater sensitivity and should be the test of choice for symptomatic cases. HSV-2 TSS is indicated for patients with genital lesions in whom antigen detection, culture or PCR fail to detect HSV, and for patients who are asymptomatic but have a history suggestive of genital herpes. HSV-2 TSS is further indicated for patients infected with HIV. HSV-2 TSS along with HSV-1 TSS may be considered, as appropriate, in evaluating infection and/or immune status in couples discordant for genital herpes, women who develop their first clinical episode of genital herpes during pregnancy, asymptomatic pregnant women whose partners have a history of genital herpes or HIV infection, and women contemplating pregnancy or considering sexual partnership with those with a history of genital herpes. The above should be performed in conjunction with counselling of infected persons and their sex partners.

Increase in intracellular Na+: transmembrane signal for rejoining of DNA strand breaks in proliferating lymphocytes.

Two early events in the mitogen-induced entry of murine splenocytes into proliferation are (a) a rapid rise in influx of Na+, causing its total internal concentration to increase by 42 +/- 7% within 2 h of culture with concanavalin A (Con A), and (b) rejoining of some 3000 DNA strand breaks per diploid genome within the same period. Con A did not induce rejoining in low Na+ (less than 9 mM) medium, but the process began directly when Na+ was added, at its usual concentration, to the growth medium. Incubation of cells with ouabain, an inhibitor of the Na+K+-ATPase, or monensin, a Na+ ionophore, caused an increase in the internal Na+ concentration in normal, but not in low, Na+ medium. In the former (but not in the latter) medium, both ouabain and monensin caused rejoining of the DNA strand breaks to occur in resting lymphocytes, i.e., in the absence of mitogen. Stimulation of splenocytes with Con A also resulted in a rapid but transient increase in the level of intracellular free Ca2+. This effect was also observed in the absence of extracellular Na+; however, deprivation of extracellular Ca2+ completely abolished this effect. Moreover, the intracellular free Ca2+ level was significantly higher in cells suspended in Na+-free buffer or medium. Since the Con A-induced rejoining of DNA strand breaks occurred in the absence of extracellular Ca2+ and removal of extracellular Na+ had no inhibitory effect on the Con A-induced increase in the level of intracellular free Ca2+, the Con A-stimulated repair could not have been mediated by the initial increase in Ca2+ influx. The early mitogen-induced increase in the internal Na+ concentration is a necessary and sufficient signal for the rejoining of breaks, an event that must occur before the proliferating lymphocytes can replicate their DNA.

Amino acid transport in pig lymphocytes. Enhanced activity of transport system asc following mitogenic stimulation.

Changes in neutral amino acid transport activity caused by addition of phytohaemagglutinin-P to quiescent peripheral pig lymphocytes have been evaluated by measurements of 14C-labelled neutral and analogue amino acids under conditions approaching initial entry rates. Utilizing methylaminoisobutyric acid, the best model substrate of System A, we confirmed our previous report (Borghetti, A.F., Kay, J.E. and Wheeler, K.P. (1979) Biochem. J. 182, 27-32) on the absence of this transport system in quiescent cells and its emergence following stimulation. Furthermore, we demonstrated the presence in quiescent cells of an Na+-dependent transport system for neutral amino acids that has been characterized as System ASC by several criteria including intolerance to methylaminoisobutyric acid, strict Na+-dependence, the property of transtimulation and specificity for pertinent substrates such as alanine, serine, cysteine and threonine. Analysis of the relationship between influx and substrate concentration revealed that two independent saturable components contribute to entry of alanine in quiescent cells: a low affinity (Km = approximately 4 mM) and a high affinity (Km = approximately 0.2 mM) component. The high affinity component could be inhibited in a competitive way by serine, cysteine and threonine, but methylaminoisobutyric acid did not change appreciably its constants. The enhanced activity of alanine transport through the ASC system observed in activated cells resulted from a large increase in the capacity (V) of the high affinity component without any substantial change in the apparent affinity constant (Km).

Chlamydia and lymphogranuloma venereum in Canada: 2003-2012 Summary Report.

BACKGROUND: Chlamydia continues to be the most commonly reported sexually transmitted infection in Canada. Lymphogranuloma venereum (LGV), caused by certain serovars of Chlamydia trachomatis, is becoming established in some populations in a number of Western countries. OBJECTIVE: To identify trends in reported cases of chlamydia and LGV in Canada from January 1, 2003 to December 31, 2012. METHODS: Notifiable disease data on chlamydia were submitted to the Public Health Agency of Canada by provincial and territorial epidemiological units and summarized at the national level by age and sex. Confirmatory testing for suspected LGV cases and serovar subtyping were performed by the National Microbiology Laboratory (NML). Where possible, provincial/territorial health authorities use a standardized national case report form to collect enhanced epidemiological data on each case and to submit the data to the Agency. RESULTS: Rates of reported cases of chlamydia increased by 57.6%, from 189.6 to 298.7 per 100,000 between 2003 and 2012. The rate of reported cases of chlamydia among females (383.5 per 100,000) was almost twice as high as that among males (212.0 per 100,000), although the highest relative rate increase occurred among males. In both males and females, the rates of chlamydia were highest in those aged 20 to 24 years. From 2004 to 2012, 170 cases of LGV were reported to the Agency by provincial health authorities (including 104 confirmed and 66 probable cases). In 2012, case reports were received on 12 confirmed and probable cases, compared to 38 laboratory-positive cases confirmed by the NML. CONCLUSION: In Canada, as in many countries, chlamydia rates have markedly increased over the last 10 years, in part due to improved diagnosis through nucleic acid amplification (NAAT) testing. Consistent with trends in Europe and other countries, LGV is emerging in Canada among men who have sex with men (MSM).

Type-specific human papillomavirus infections and Pap test findings in Inuit and non-Inuit women in Nunavut, Canada.

OBJECTIVE: To determine the prevalence and distribution of type-specific human papillomavirus (HPV) infections and their association with cytological outcomes in women living in the Canadian territory of Nunavut. METHODS: Surveillance of type-specific HPV infection was conducted. Cervical specimens of all Inuit, First Nations and non-Aboriginal women in Nunavut who presented for a Pap test in any clinical setting between January 2008 and March 2009 were tested for HPV infection. The association between high-grade cervical lesions and HPV type was also examined. RESULTS: HPV results were available for 4,043 individual women (13 to 77 years). Of those with known ethnicity (N=4,033), 89.2% were Inuit, 0.4% were First Nations and 10.4% were non-Aboriginal. First Nations women were included in all analyses except those making comparisons by ethnicity, due to the small number of individuals in this group. Overall, 29.9% of women were found to be infected with HPV (any type) and 19.9% with any high-risk HPV (type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 or 59). Most often, women were infected with HPV 16 (6.4%) followed by HPV 31 (3.1%). There were no statistically significant differences between Inuit and non-Aboriginal (reference group) women 20 years of age and older regarding the prevalence of any HPV (odds ratios (OR): 1.19, 95% confidence intervals (CI): 0.92-1.54), high-risk HPV (OR: 1.06, 95% CI: 0.78-1.44) or HPV 16 and 18 (OR: 0.81, 95% CI: 0.51-1.27). HPV 31 was the only type that was significantly more frequent among Inuit than non-Aboriginal women (OR: 3.95, 95% CI: 1.24-12.54). There was no difference in the overall occurrence of cervical abnormalities between non-Aboriginal and Inuit women (p-value = 0.17). HPV 16 was strongly associated with cervical dysplasia, being present in 50.9% of specimens with a high-grade lesion. CONCLUSION: HPV is a significant public health issue in the territory of Nunavut. The findings presented in this article are similar to those in other studies among Inuit women, with prevalence of HPV being higher than in studies conducted among non-Inuit women in other regions of Canada. These results provide a baseline of HPV prevalence that precedes the introduction of the Nunavut HPV Immunization Program in 2010 and will allow for future evaluation. The high prevalence of HPV infection among women living in Nunavut can be reduced through immunization and associated high-grade cervical abnormalities mitigated by regular cervical screening.

Inherited diseases in North American Mennonites: focus on Old Colony (Chortitza) Mennonites.

The patterns of migration and the genetic disorders occurring among North American Mennonites are reviewed, and inherited conditions recently recognized in a religious and genetic isolate, the Old Colony (Chortitza) Mennonites, are described. Old Colony Mennonites are of Dutch/German origin and descend from approximately 400 founding families who settled in the Old Colony, Chortitza (the Ukraine, USSR) in the late 1700s, and then migrated to Canada and Central and South America in the past century. We investigated over 6 generations of a Canadian Old Colony kindred in which there was extensive intermarriage, and in whom 28 individuals developed diabetes mellitus. Insulin-dependent diabetes mellitus (IDDM) occurred in 14 affected individuals in 10 closely related sibships; the 11 living IDDM patients were all concordant for the immunogenetic marker HLA-DR4. Fourteen close relatives had other disorders of carbohydrate metabolism, including gestational diabetes and non-insulin-dependent diabetes mellitus. Other close relatives had autoimmune diseases, including rheumatoid arthritis, hyper- and hypothyroidism, multiple sclerosis, and red cell aplasia. Other inherited diseases, including Alport syndrome, congenital defects, and inborn errors of metabolism were also found in the kindred. In the almost exclusively (99%) Old Colony Mennonite public health district in which the kindred was ascertained, there were multiple cases of Tourette syndrome, of malformations (including congenital heart defects and cleft lip +/- palate), and familial clusters of inborn errors of metabolism. We report this Old Colony (Chortitza) Mennonite isolate because 1) there are large familial aggregations of tissue-specific autoimmune diseases, malformations, inborn errors of metabolism, and of some other conditions whose genetic basis is still unknown; 2) there are multiple cases of rare genetic conditions, 3) we have established a computerized genealogic data base on over 1,000 kindred members as well as a cryopreserved lymphocyte/DNA bank on over 100 closely related individuals with various genetic conditions; and 4) this religious isolate, which extends across North, Central, and South America, offers an excellent opportunity for studying the epidemiology and molecular genetics of both common and rare inherited diseases.

Suprapubic cystotomy as treatment for severe hemorrhagic cystitis after bone marrow transplantation.

We analyzed the success of suprapubic cystotomy in patients with severe hemorrhagic cystitis after bone marrow transplantation. Seventy-three out of 963 patients developed severe hemorrhagic cystitis which resulted in urinary tract obstruction after high-dose cytoreductive therapy. Eleven patients (15%) failed medical treatment and required emergency suprapubic cystotomy. Three of these patients died of other complications prior to resolution of HC. Of the remaining 8 patients who underwent surgery, 4 are alive. The mortality rate was significantly higher in patients who required surgery than in those who responded to medical therapy. Patients whose HC required surgery also had a greater transfusion requirement than those who responded to medical therapy. We conclude that surgical treatment of severe HC should be undertaken only after failure of medical therapy.

The occurrence of cholangitis after percutaneous biliary drainage: evaluation of some risk factors.

Sepsis of the biliary tract is often reported after percutaneous transhepatic biliary drainage (PTBD) and is considered a life-threatening condition. The authors studied 39 patients with biliary stenosis (35 with neoplastic stricture and four with benign disease) with the purpose of identifying some factors possibly associated with a higher risk of cholangitis. None of the patients complained of biliary sepsis at the first clinical examination. Several factors were taken into account and were statistically tested according to Miettinen rate ratios to differentiate patients in whom cholangitis would consequently develop: nature, site and extent of basic disease, type and functioning of PTBD, skin contamination at puncture site of PTBD, and bile contamination at PTBD and at follow-up. The presence of bacteria in the first bile (31.5%) was not related to a higher risk. All subjects showed bile contamination after PTBD, but cholangitis developed in only 15 patients, and it was always supported by enteric microorganisms. When we compared patients with cholangitis and subjects without infection, it was possible to demonstrate a statistically significant association of cholangitis and the following: nature of the stricture, presence of multiple intrahepatic biliary obstruction, neoplastic invasion or compression on the duodenum, and presence of Staphylococcus aureus on the skin at puncture site at drainage.