Eija Hiltunen-Back

Subtly Impaired Humoral Immunity Predisposes to Frequently Recurring Genital Herpes Simplex Virus Type 2 Infection and Herpetic Neuralgia

BACKGROUNDnImmunogenetic factors predisposing to recurrent genital herpes remain poorly characterized.nnnMETHODSnIn a prospective case-control study, 52 consecutive patients with frequently recurring outbreaks of genital herpes were compared with 80 herpes simplex virus (HSV)-seropositive (types 1 and 2) and 70 HSV-seronegative control subjects. Immunoglobulins (Igs), type-specific anti-HSV-2 IgG and IgG subclass antibodies against glycoprotein G, levels of C3 and C4, and classical pathway hemolytic complement activity were measured, and IgG1 and IgG3 allotyping; C4 immunophenotyping; C4* real-time polymerase chain reaction (PCR) genotyping; and HLA-A*, B*, and DR* typing were performed.nnnRESULTSnThe G3m(g),G1m(a/a(x)) haplotype was more frequent in patients than in HSV-seronegative control subjects (P=.047). Compared with all control subjects, low levels of total IgG1 (odds ratio [OR], 4.9 [95% confidence interval {CI}, 2.0-12.5]; P=.001) and IgG3 (OR 3.6 [95% CI 1.7-7.8]; P=.001), but not of anti-HSV-2 antibodies, were associated with recurrences. Levels of complement were lowest in patients. The C4* null type was negatively associated with neuralgia (OR, 0.2 [95% CI, 0.06-0.81]; P=.022).nnnCONCLUSIONSnLow levels of antibody-dependent cellular cytotoxicity-mediating IgG1 and IgG3 antibodies, partly dependent of allotype, may predispose to recurrent genital herpes. Antibodies produced by T helper type 1 responses, potentially against an unknown epitope, appear to be relevant in recurrences. In patients, C4* deficiencies are associated with protection from herpetic neuralgias, possibly through reduced inflammation.

Nationwide increase of Chlamydia trachomatis infection in Finland: highest rise among adolescent women and men.

Background Since 1995, the incidence of Chlamydia trachomatis infection has been increasing in Finland, although there have been no major changes in public sexually transmitted disease (STD) services or screening practice. Objectives The objective was to study whether the change in C. trachomatis incidence is significant and to identify specific risk groups. Methods The incidence rates for all C. trachomatis cases notified by laboratories to the National Infectious Disease Register (NIDR) in Finland in 1995-2000 were calculated by gender, age, and domicile. Data from a sentinel STD surveillance network was used to analyze changes of risk-taking behavior in age groups with the highest C. trachomatis rates. Results During the 6-year study period, laboratory surveillance data documented an increase in the incidence rate from 23.4 per 10,000 to 29.2 per 10,000. The increase was most evident among people living in nonurban densely populated areas. Highest increase, 1.37-fold (95% confidence interval [CI], 1.29-1.46) in women and 1.69-fold (CI, 1.47-1.92) in men, occurred in the youngest age group (10-19 years old). In 2000, more women, but not men, in the age group of 10-29 years reported 5 or more annual sex partners (18.8%; CI, 16.3-21.6) than in 1995 (8.3%; CI, 5.7-11.5). Conclusion National surveillance of C. trachomatis infection based on laboratory notification documented increasing incidence rates, especially among adolescents and young people. This risk group should be a target for screening and educational programs to control the epidemic of C. trachomatis infections.

A nationwide sentinel clinic survey of chlamydia trachomatis infection in Finland.

Background Chlamydia trachomatis has been recognized as a major sexually transmitted infection in North America and Western Europe during the past two decades. The incidence of C trachomatis in Finland has been continuously high throughout the 1990s. Objectives As the epidemic of C trachomatis infection continues in Finland, there is a need to obtain up-to-date information on the prevalence and patient profiles in the planning of preventive strategies. Methods A nationwide sentinel clinic network consisting of seven sexually transmitted disease (STD) and five general student health clinics was established in 1995. Data were collected during a 3-year period (1995–1997) from 3,686 patients with and 32,230 patients without C trachomatis using a self-administered questionnaire. Results The prevalence of chlamydia was 8.4% in the STD clinics and 5.3% in the general clinics; 90% of the infections were endemic. The prevalence was highest in the youngest age group (15–19 years; 16% in females, 14% in males). The patients with chlamydia were significantly younger (mean age: men 26.6 years, women 23.7 years) than those without chlamydia. Women with chlamydia used oral contraceptives or intrauterine devices (IUD) significantly more often (59%) than women without chlamydia (42%). A high number of sex partners and a history of previous chlamydia during the preceding 12 months were also risk factors. Men contracted chlamydia frequently from a casual partner (61%) but rarely from a commercial sex worker (2%). For women, the source partner was most often a regular one (61%). The median time from exposure to attendance was 34 days, and was highest when the source partner was a spouse. One third of the patients could have spread chlamydia to a new partner before the diagnosis. Conclusions C trachomatis infection is spread all over Finland, and the risk factors include younger age, high number of sex partners, and use of oral contraceptives or IUDs. Source partner analysis focused attention on the importance of transmission from regular partners, especially in women. The time from transmission to diagnosis was long, and any effort to shorten this period would be an effective preventive strategy.

Epidemics due to imported syphilis in Finland

Background Russia and other states of the former Soviet Union experienced a huge increase in syphilis beginning in the early 1990s. At first these epidemics were not well known in neighboring countries such as Finland. Study Design In 1995 the incidence of syphilis in Finland doubled to 3.3/100,000 and a local cluster of 18 cases was detected in the city of Tampere. The reasons for this epidemic were analyzed and the occurrence of syphilis was carefully monitored up to 2001. Results The main reason for the increased incidence in Finland was the import of syphilis from Russia; only a few cases were acquired from Estonia or elsewhere. The source partners of Finnish men who contracted syphilis abroad were mostly sex workers or other casual partners. Mobile prostitution to Finland was not involved in the transmission. Most syphilis cases were found sporadically in southern Finland, in areas where foreign travel is frequent. Secondary transmission in Finland was usually limited to one or two partners. The only isolated cluster was further away and developed due to unawareness of the risk of syphilis by the cases and local healthcare providers. From 1995 onward, syphilis was carefully monitored by national reporting and a special sexually transmitted disease (STD) surveillance network, and the incidence remained at a constant level even though travel to and from Russia more than tripled. Nationwide serologic surveillance in STD and maternity clinics and among blood donors showed no major changes in the prevalence of syphilis. Conclusion An epidemic of syphilis imported mainly by heterosexual men from Russia caused one sporadic cluster in Finland in 1995. Thereafter, general awareness by the public and healthcare providers about the risks of contracting syphilis from abroad, in addition to effective use of national surveillance and notification systems, was needed to protect the country from further spread of syphilis to an endemic infection.

Mannose-binding lectin 2 gene polymorphism in recurrent herpes simplex virus 2 infection

Mannose-binding lectin (MBL) is a complement component and an opsonic factor recognizing and binding to herpes simplex virus 2 (HSV-2). In this study, we assessed the effect of MBL2 genotypes on the risk of recurring HSV-2 infection. The MBL2 structural variant genotype (A/O or O/O) was more common among the patients with recurrent HSV-2 infection compared with healthy controls (47% vs 26%, respectively; odds ratio [OR] = 2.6, 95% confidence interval [CI] 1.3-4.9; p = 0.005) or controls positive for HSV-2 antibodies (15%; OR 4.9, 95% CI 1.5-16; p = 0.007). Thus, we conclude that the MBL2 structural variant genotype, possibly through impaired recognition of HSV-2, seems to predispose individuals to the development of recurring HSV-2 infection.

Genotyping of Chlamydia trachomatis in rectal and pharyngeal specimens: identification of LGV genotypes in Finland

Objectives Lymphogranuloma venereum (LGV) infections caused by Chlamydia trachomatis L types have recently emerged in Europe among HIV-positive men having sex with men. Our aim was to introduce a genotyping strategy suitable for a diagnostic laboratory using nucleic acid amplification tests (NAATs) for detection of C trachomatis and to investigate the prevalence of LGV types in rectal and pharyngeal specimens in Finland. Methods Aptima Combo 2 (Gen-Probe) was used to detect C trachomatis in swabs. Altogether 140 C trachomatis NAAT-positive rectal and pharyngeal samples were genotyped by pmpH and ompA real-time PCR. Results Of the 140 NAAT-positive rectal and pharyngeal specimens, 114 (81%) were successfully typed by pmpH PCR. One hundred and four samples contained non-LGV, nine samples LGV and one sample both non-LGV and LGV C trachomatis types. The C trachomatis LGV types were mainly found in rectal samples. Six of the L types were confirmed to be genotype L2b and two were L2 with ompA PCR and sequencing. Conclusions Our experience suggests that genotyping C trachomatis by pmpH PCR can be introduced as a function of a diagnostic laboratory already using NAAT for detection of C trachomatis. The data show that LGV infections occur also in Finland. LGV should be taken into account when considering treatment and management of rectal C trachomatis infections.

Rapid decrease of endemic gonorrhea in Finland

Objectives: The incidence of gonorrhea has decreased in several European countries while a recent epidemic has occurred in Russia and the Baltic countries. In 1990, Finland had a higher gonorrhea incidence than the other Nordic countries. Therefore we studied prospectively the epidemiology of gonorrhea with special reference to the endemic or imported source of infection. Study Design: The study included three gonorrhea patient series from STD clinics in Helsinki in 1990 to 1995. Each series covered a 12‐month period. Case controls with Chlamydia trachomatis infection were included. Demographic and epidemiological findings, including source partner profiles, were analyzed. Results: Gonorrhea decreased rapidly during the study period. In 1990 to 1991, there were 490 patients (3.3% of all patient visits); in 1992 to 1993, 162 (1.3%); and in 1994 to 1995, only 92 patients (0.9%) with gonorrhea. The change in the prevalence was highly significant (p < 0.0001) and was entirely because of the decreased number of endemic infections. The rate of imported gonorrhea remained constant with 50 to 60 patients, although traveling had increased markedly to Russia and Estonia where the incidence of gonorrhea was very high. Thirty‐one percent of the patients with endemic gonorrhea but only 14% with imported gonorrhea (p < 0.0001) had a concomitant C. trachomatis infection. The prevalence of chlamydia decreased from 10.2 to 8.1% (p < 0.001), but in contrast to gonorrhea the source of infection was mainly endemic (89% to 97%) during the whole study period. The patients with gonorrhea were older and had a higher frequency of casual source partners than those with chlamydia. Overall, from 80% to 74% of the men and from 48% to 33% of the women had contracted infection from a casual partner. Conclusion: The present study documented a rapid decrease of endemic gonorrhea in Finland, whereas the rate of imported gonorrhea remained constant. Demographic findings or source partner profiles of patients with gonorrhea or chlamydia gave no obvious explanation for the rapid decline of endemic gonorrhea, which is in sharp contrast to C. trachomatis infection.

Chlamydia trachomatis Infection Induces Replication of Latent HHV-6

Human herpesvirus-6 (HHV-6) exists in latent form either as a nuclear episome or integrated into human chromosomes in more than 90% of healthy individuals without causing clinical symptoms. Immunosuppression and stress conditions can reactivate HHV-6 replication, associated with clinical complications and even death. We have previously shown that co-infection of Chlamydia trachomatis and HHV-6 promotes chlamydial persistence and increases viral uptake in an in vitro cell culture model. Here we investigated C. trachomatis-induced HHV-6 activation in cell lines and fresh blood samples from patients having Chromosomally integrated HHV-6 (CiHHV-6). We observed activation of latent HHV-6 DNA replication in CiHHV-6 cell lines and fresh blood cells without formation of viral particles. Interestingly, we detected HHV-6 DNA in blood as well as cervical swabs from C. trachomatis-infected women. Low virus titers correlated with high C. trachomatis load and vice versa, demonstrating a potentially significant interaction of these pathogens in blood cells and in the cervix of infected patients. Our data suggest a thus far underestimated interference of HHV-6 and C. trachomatis with a likely impact on the disease outcome as consequence of co-infection.

Chlamydia trachomatis Genotypes and the Swedish New Variant among Urogenital Chlamydia trachomatis Strains in Finland

Our aims were to genotype Chlamydia trachomatis strains present in urogenital samples and to investigate the occurrence of the Swedish new variant of C. trachomatis in Finland. We genotyped 160 C. trachomatis positive samples with ompA real-time PCR and analyzed 495 samples for the new variant. The three most prevalent genotypes were E (40%), F (28%), and G (13%). Only two specimens containing bacteria with the variant plasmid were detected. It seems that in Finland the percentage of infections due to genotypes F and G has slightly increased during the last 20 years. Genotypes E and G appear to be more common, and genotypes J/Ja and I/Ia appear to be less common in Europe than in the USA. Although the genotype E was the most common genotype among C. trachomatis strains, the new variant was rarely found in Finland.

An increasing proportion of reported Chlamydia trachomatis infections are repeated diagnoses.

Background In recent decades, increasing rates of Chlamydia cases have contrasted with decreasing Chlamydia trachomatis seroprevalence rates and decreasing Chlamydia-associated complication rates. We elucidated the conflicting trends by studying incidence of repeated Chlamydia infections over time. Methods Chlamydia cases reported during 1995 to 2009 were identified in the Finnish National Infectious Diseases Registry. Trends of single and repeated diagnoses of Chlamydia infection were analyzed. Results Our study population comprised 147,148 individuals with a total of 177,138 genital chlamydial infections. The proportion of annual repeated diagnoses of genital infections increased among female and males from 4.9% to 7.3% and from 3.8% to 5.3%, respectively. In 2009, 24.8% of the females and 20.3% of the males had had an earlier Chlamydia infection ever during the follow-up time. Of all the repeated diagnoses, 34.1% occurred within 12 months. The highest rates of repeated infection diagnoses occurred in 25-year-old women (37.0%) and in 29-year-old men (30.9%) in a cohort of individuals born in 1979. Conclusions A gradual increase of repeated Chlamydia infections resulted in 43% increase in annual infections between 1996 and 2009. The result is supportive of the existing seroprevalence data suggesting that Chlamydia infection burden is not increasing in the whole population. The increasing infection rates in males, in particular, justify development of effective strategy in preventing reinfections and onward transmission.