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Pregnancy outcome in recurrent aborters is not influenced by Chlamydia IgA and/or G.

PROBLEM: It is unclear whether chlamydia infection influences the miscarriage rate and immunological factors in patients with recurrent miscarriage. METHOD OF STUDY: Chlamydia DNA, IgA and IgG to Chlamydia trachomatis, natural killer cell activity, complement 3 (C3), C4, hemolytic complement, antinuclear antibodies, antiphospholipid antibodies, prolactin, activated partial thromboplastin time, prothrombin time and fibrinogen were examined in 504 patients with a history of two or more consecutive first-trimester miscarriages. Subsequent pregnancy outcomes were compared between cases with and without antibodies to C. trachomatis. RESULTS: Totals of 10 of 30 and 48 of 201 patients receiving no medication miscarried subsequently with and without chlamydia infection. Chlamydia IgA and/or IgG were associated with a high level of C3 but not other immunological and coagulatory parameters. CONCLUSION: Antibodies to C. trachomatis do not influence subsequent pregnancy outcome in patients with a history of recurrent miscarriage.

Abortion, Habitual↗

[Immune response against Chlamydia trachomatis inoculation in mice--changes in interferon activity, antibody titers and weight of the spleen as parameters of infection].

We examined the immune response against Chlamydia trachomatis (serovar L2) inoculation in mice by measuring the serum interferon (IFN) level, 2'-5'A synthetase (2-5A(S] activity, antibody titers (IgM, IgG) and the spleen weight as parameters of infection. The interferon activity was detected 6 hrs (400 U/ml) and the activity peaked 12 hrs (450 U/ml) after inoculation, and then gradually decreased thereafter (24 hrs: 12 U/ml, 36 hrs: undetectable). It was found that Chlamydia trachomatis induces IFN as well as bacteria. To monitor the behavior of IFN action after serum IFN was cleared, 2-5A(S) activity in the spleen cell extract was measured. It was found that the activity reached its peak 1 to 2 days after inoculation and then decreased as well as in infectivity of Chlamydia trachomatis. The activity however was almost not detected in sera of mice after inoculation of heat-inactivated Chlamydial organism (56 degrees C, 10 min). This may indicate that intact Chlamydial organisms were required for induction of IFN. IFN induced in mice was stable in pH 2.0 treatment and IFN induced by Newcastle disease virus inhibited growth of Chlamydia trachomatis in L929 cell cultures in a dose-dependent manner. The weight of the spleen gradually increased and reached its peak (2- to 3-fold of the control) in 3 to 5 days after inoculation, and then gradually decreased to the control level. IgM and IgG antibodies to Chlamydia trachomatis were detected by immunofluorescence method and enzyme-linked immunosorbent assay, respectively. The antibody IgM was detected as early as 2 days and reached its peak 3 to 4 days after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effect of storage conditions on the infectivity of Chlamydia pneumonia].

In order to facilitate the isolation of C. pneumoniae, strain similar TWAR, with high frequency, we investigated the effect of various factors on the infectivity of Chlamydia using two laboratory strains, C. pneumoniae TWAR and C. trachomatis serovar D. The factors tested were the effects of different temperatures for storage conditions, saliva from healthy person, storage media for Chlamydia, and the frequency of freezing and thawing. Chlamydial suspension was prepared in the two media, SPG (sucrose-phosphate-glutamate buffer pH 7.5), and CT-GM (culture medium for Chlamydia which contains 1 micrograms/ml cycloheximide and 0.04% glucose). Chlamydial suspension was allowed to stand in each of four different thermal conditions: 37 degrees C, room temperature (25 degrees C), 4 degrees C, 0 degrees C and -75 degrees C for 1, 3, 6, 24, 48, 72, 96, 120 and 144 hours. For storage at -75 degrees C, one of three groups of glass vial tubes containing Chlamydia was covered with an "airmat" to prevent the rapid freezing of Chlamydia. The effect of various factors on the infectivity was assayed by inoculation of the suspension on HeLa 229 cell monolayers. Results showed that the infectivity rapidly decreased at 37 degrees C and room temperature, while at 4 degrees C, 0 degrees C and -75 degrees C, relatively high infectivity was maintained and contained until days 4 to 6. This decreasing pattern was similar to among the media used. We were not able to find any differences in the infectivity among the samples with or without the "airmat".(ABSTRACT TRUNCATED AT 250 WORDS)

Chlamydia↗

[Evaluation of a synthetic peptide based species specific EIA kit for detection of antibodies to Chlamydia trachomatis with clinical specimens].

We have evaluated a new kit, PEPTIDE Chlamydia (Meiji Milk Products Co., Ltd, Tokyo), for detecting species specific antibodies to Chlamydia trachomatis with synthetic peptide as an antigen. Serum samples from women with C. trachomatis cervicitis (n = 45), healthy pregnant women (n = 100), and children suffering from C. pneumoniae lower respiratory tract infection (n = 9) were used. We have measured the serum IgG or IgA antibodies to C. trachomatis of those sera with PEPTIDE, Sero IPALIZA Chlamydia (Savyon Diagnostics, Israel), and HITAZYME Chlamydia (Hitachi Chemical Co., Ltd, Hitachi). Serum samples with discrepant results were further analyzed by a microimmunofluorescence test and immunoblotting (western blotting). IgG and IgA serum positive rate to C. trachomatis of sera from women with C. trachomatis cervicitis were similar in three kits, that is, 91% and 80% in PEPTIDE, 89% and 82% in Sero IPALIZA, and 84% and 76% in HITAZYME, respectively. IgG and IgA serum positive rate to C. trachomatis of sera from healthy pregnant women were 18% and 9% in PEPTIDE, 12% and 15% in Sero IPALIZA, and 15% and 13% in HITAZYME, respectively. Serum antibodies to C. trachomatis in serum samples from children with C. pneumoniae infection were all negative in PEPTIDE, but falsely positive in several cases in Sero IPALIZA or HITAZYME. In sera with discrepant results, PEPTIDE gave more identical results with a micro-IF test and immunoblotting analysis than Sero IPALIZA or HITAZYME. These results indicate that PEPTIDE is an useful kit to detect more species specific antibodies to Chlamydia trachomatis than former kits.

Antibodies, Bacterial↗

Susceptibility of prostate epithelial cells to Chlamydia muridarum infection and their role in innate immunity by recruitment of intracellular Toll-like receptors 4 and 2 and MyD88 to the inclusion.

Although Chlamydia infections are widespread throughout the world, data about immunopathogenesis of genitourinary tract infections in males are very limited. In the present work we present an in vitro model of male genital tract-derived epithelial cells, more precisely prostate epithelial cells (PEC), to analyze if they are susceptible and able to respond to Chlamydia muridarum infection. Our results demonstrate that rat PEC are susceptible to C. muridarum infection and respond to this pathogen by up-regulating different proinflammatory cytokine and chemokine genes that could participate in the recruitment and local activation of immune cells, therefore influencing innate and adaptive immune responses during Chlamydia infection. Moreover, we analyzed the expression of Toll-like receptor 4 (TLR4), TLR2, and related molecules on PEC and the effect of C. muridarum infection on their expression. Our results demonstrate that PEC express significant levels of TLR4, CD14, TLR2, and the adaptor molecule MyD88 and up-regulate these proteins in response to C. muridarum infection. Indeed, TLR4, CD14, TLR2, and the adaptor MyD88 are specifically recruited to the vicinity of the bacterial inclusion, suggesting that these TLRs are actively engaged in signaling from this intracellular location in these cells. This is, to our knowledge, the first time that an in vitro model of infection with Chlamydia of male tract-derived epithelial cells has been achieved, and it provides the opportunity to determine how these cells respond and participate in modulating innate and adaptive immune response during Chlamydia infections.

Active Transport, Cell Nucleus↗

Interaction between Chlamydia spp. and human polymorphonuclear leukocytes in vitro.

Chlamydia psittaci and Chlamydia trachomatis elementary bodies (EB) incubated in the presence of complement or specific antibody or both caused chemotaxis of human polymorphonuclear leukocytes (PMN) in vitro. Reticulate bodies and culture supernatants had no effect on these cells. The ability of chlamydiae to enter and survive in PMN under nonopsonizing conditions was investigated by measuring the association of 3H-labeled EB and of inclusion-forming units with these phagocytes. Both assays indicated that C. psittaci as well as C. trachomatis EB are efficiently internalized. The mechanism by which this is accomplished is distinct from classical phagocytosis in that it is not dependent upon the presence of complement or antibody. Furthermore, uptake of at least C. psittaci appeared to be rapid, with no additional increase occurring after 15 min. The majority of cell-associated chlamydiae were rendered acid soluble or noninfectious within 1 h. Subsequently, there was a small but steady loss of infectivity for up to 10 h, which may have been due to the conversion of EB to the noninfectious reticulate-body form of the organism. However, even at 10 h after entry a small percentage of bacteria was still capable of infecting a second target cell. This is noteworthy in that PMN are relatively short-lived cells, and after lysis, intracellular organisms may be free to infect adjacent tissue. Electron microscopic observations were consistent with the data on uptake and persistence. The ability of a small percentage of infecting chlamydiae to maintain infectivity in PMN for at least several hours may enable these organisms subsequently to establish productive infection in permissive host cells.

Blood Bactericidal Activity↗

Chemical, biological, and immunochemical properties of the Chlamydia psittaci lipopolysaccharide.

The lipopolysaccharide (LPS) of Chlamydia psittaci was extracted from yolk sac-grown elementary bodies, purified, and characterized chemically, immunochemically, and biologically. The LPS contained D-galactosamine, D-glucosamine, phosphorus, long-chain fatty acids, and 3-deoxy-D-manno-2-octulosonic acid in the molar ratio of approximately 1:2:2:6:5. The antigenic properties of the isolated LPS were compared with those of the LPS from Chlamydia trachomatis and Salmonella minnesota Re by the passive hemolysis and passive hemolysis inhibition tests, absorption, hydrolysis kinetics, and Western blot analysis with rabbit polyclonal antisera against chlamydiae and with a mouse monoclonal antibody recognizing a genus-specific epitope of chlamydial LPS. Two antigenic determinants were identified, one of which was chlamydia specific and the other of which was cross-reactive with Re LPS. Both determinants were destroyed during acid hydrolysis, whereby a third antigen specificity was exposed which was indistinguishable from the lipid A antigenicity. In rabbit polyclonal antisera prepared against Formalin-killed elementary bodies or detergent-solubilized membranes, two antibody specificities were differentiated. One of these was chlamydia specific, and the other was cross-reactive with Re LPS. The LPS of C. psittaci was inactive within typical endotoxin parameters (lethal toxicity, pyrogenicity, local Shwartzman reactivity); it was, however, active in some in vitro assays, such as those testing for mouse B-cell mitogenicity and the induction of prostaglandin E2 in mouse peritoneal macrophages.

Abortion, Veterinary↗

Production of colony-stimulating factors during pneumonia caused by Chlamydia trachomatis.

The colony-stimulating factors (CSFs) are cytokines involved in the production, differentiation, and activation of host phagocytes. During murine infection with Chlamydia trachomatis (MoPn), plasma CSF levels increased in euthymic (nu/+) and athymic (nu/nu) BALB/c mice. Levels declined later in infection, with the nu/+ mice resolving the infection but the nu/nu mice succumbing by day 16. Either live or heat-killed Chlamydia organisms could induce CSF increases on day 7 postchallenge in nu/+ mice; however, by day 14, only mice challenged with live organisms maintained high plasma levels. CSFs were also produced by spleen cells of nu/+ and nu/nu mice in response to Chlamydia antigen. Spleen cell CSF production was detectable by days 3 to 5 postinfection. In nu/+ mice, spleen cell CSF production was elevated throughout the rest of the time course but in nu/nu mice fell significantly at day 14. Like the plasma CSF activity (CSA) production, spleen cell CSA production on day 7 was seen in mice challenged with either live or heat-killed Chlamydia organisms, but on day 14 only nu/+ mice challenged with live organisms maintained significant CSA production. To further characterize the T-cell dependence of CSA production, spleen cells of nu/+ mice were depleted of T cells or T-cell subsets before producing supernatants. On day 14 postinfection, the CD4+ lymphocyte was the major producer of CSFs. Additionally, there were different types of CSFs secreted by nu/+ and nu/nu mice as determined by the ability of spleen cell supernatants to support the granulocyte-macrophage CSF/interleukin 3-dependent cell line FDCP-1. Supernatants from nu/+ mice had 4 to 8 times the level of FDCP-1 CSF activity of the supernatants from nu/nu mice. These results support the evidence that nu/+ mice were producing some CSFs by T-cell-dependent mechanisms. This is the first report of CSF production in vivo during Chlamydia infection. Furthermore, we show that CSFs are produced by both T-cell-dependent and T-cell-independent mechanisms. The capacity of the CSFs to increase the production and effector function of phagocytes may be important to host defenses.

Animals↗

Selective translocation of annexins during intracellular redistribution of Chlamydia trachomatis in HeLa and McCoy cells.

When Chlamydia trachomatis elementary bodies enter epithelial cells, they occupy membrane-bound vesicles that aggregate with each other in a calcium-dependent manner but that do not fuse with lysosomes. As members of the annexin family of calcium- and membrane-binding proteins have been implicated in mediating calcium-regulated membrane traffic during endo- and exocytosis, we examined the intracellular localization of certain annexins following invasion of HeLa and McCoy cells by C. trachomatis serovar L2. Immunofluorescence staining with a panel of polyclonal antibodies against five human annexins revealed that annexins III, IV, and V translocate within the cytoplasm to the proximity of intracellular chlamydiae whereas the distribution of annexins I and VI was unaffected. The distinct distribution of annexins I and III was further analyzed by confocal microscopy, which revealed an intimate association between chlamydial aggregates or inclusions and annexin III. Confocal microscopy also confirmed the nonassociation of annexin I with chlamydial aggregates. Depletion of intracellular Ca2+ did not prevent association of annexin III with individual elementary body-containing endosomes but did prevent formation of chlamydial aggregates and translocation of annexin III. Furthermore, chloramphenicol-treated cells also showed association between chlamydial aggregates and annexin III, indicating that the annexins are of host cell origin. These data suggest that certain cytosolic annexins may be involved in the Ca(2+)-dependent aggregation and fusion of chlamydia-containing vesicles. The fact that these Ca(2+)-binding proteins differ in their ability to associate with chlamydia-containing vesicles and inclusions implies that the factors that regulate the interaction of annexin I and annexin III with membrane are different and suggests a selective regulatory mechanism for endosome aggregation and avoiding lysosome fusion during chlamydia infection.

Annexins↗

Gamma interferon production by cytotoxic T lymphocytes is required for resolution of Chlamydia trachomatis infection.

In this study, we used mice in which the gene for gamma interferon (IFN-gamma) has been disrupted (IFN-gamma-/- mice) to study the role of this cytokine in the resolution of Chlamydia trachomatis infection. We show that IFN-gamma-/- mice are impaired in the ability to clear infection with C. trachomatis compared to IFN-gamma+/+ control mice. Activated CD8(+) cytotoxic T lymphocytes (CTL) secrete IFN-gamma in response to intracellular infection, and we have shown previously that a Chlamydia-specific CTL line can reduce C. trachomatis infection when adoptively transferred into infected mice. In the present study, we found that when these IFN-gamma+/+ CTL lines are transferred into Chlamydia-infected IFN-gamma-/- mice, the transferred CTL cannot overcome the immune defect seen in the IFN-gamma-/- mice. We also show that Chlamydia-specific CTL can be cultured from IFN-gamma-deficient mice infected with C. trachomatis; however, the adoptive transfer of IFN-gamma-/- CTL into infected IFN-gamma+/+ mice does not reduce the level of infection. These results suggest that IFN-gamma production by CTL is not sufficient to overcome the defect that IFN-gamma-/- mice have in the resolution of Chlamydia infection, yet IFN-gamma production by CTL is required for the protective effect seen upon adoptive transfer of CTL into IFN-gamma+/+ mice.

3T3 Cells↗

Route of infection that induces a high intensity of gamma interferon-secreting T cells in the genital tract produces optimal protection against Chlamydia trachomatis infection in mice.

The induction of local T helper type 1 (Th1)-mediated cellular immunity is crucial for resistance of mice to genital infection by the obligate intracellular bacterium Chlamydia trachomatis. We tested the hypothesis that the route of immunization that elicits relatively high numbers of chlamydia-specific, gamma interferon (IFN-gamma)-secreting T lymphocytes (ISTLs) in the genital tract would induce optimal protective immunity against reinfection. Female BALB/c mice were infected intravaginally (i.v.), intranasally (i.n.), orally (p.o.), or subcutaneously (s.c.) with C. trachomatis. At days 7, 14, 21, and 28 postinfection, T cells isolated from the genital tract tissues were restimulated with chlamydial antigen in vitro, and the amounts of IFN-gamma induced were measured by a sandwiched enzyme-linked immunosorbent assay method. At day 7 postinfection, i.n.- and i.v.-immunized mice had high levels of chlamydia-specific ISTLs in their genital tracts (203.58 +/- 68.1 and 225.5 +/- 12.1 pg/ml, respectively). However, there were no detectable ISTLs in the genital tracts of p.o.- or s.c.-infected mice. When preinfected mice were challenged i.v. 70 days later, animals preexposed by the i.n. route were highly resistant to reinfection, with greatly reduced chlamydial burden, and suffered an attenuated infection that resolved by day 6 postchallenge. Animals preexposed by the i.v. route were modestly protected, whereas p.o. and s.c. groups were indistinguishable in this regard from control mice. The resistance of i.n.-immunized mice (and to some extent the i.v.-exposed mice) to reinfection was associated with early appearance (within 24 h) of high levels of genital ISTLs compared with mice preinfected by other routes. Furthermore, although i.n. and i.v.-immunized mice had comparable levels of chlamydia-specific immunoglobulin A (IgA) antibodies in their vaginal washes, the levels of IgG2a were four- sixfold higher in i.n.-immunized mice than in any of the other groups. The results suggested that immunization routes that foster rapid induction of vigorous genital mucosal cell-mediated immune (CMI) effectors (e.g., IFN-gamma), the CMI-associated humoral effector, IgG2a, and to some extent secretory IgA produce protective immunity against chlamydial genital infection. Therefore, i.n. immunization is a potential delivery route of choice in the development of a vaccine against Chlamydia.

Administration, Intranasal↗

Qualitative analysis of psychosocial impact of diagnosis of Chlamydia trachomatis: implications for screening.

OBJECTIVES: To investigate the psychosocial impact for women of a diagnosis of Chlamydia trachomatis and discuss the implications for the proposed UK chlamydia screening programme. DESIGN: Qualitative study with semistructured interviews. Interview transcripts analysed to identify recurrent themes. PARTICIPANTS: Seventeen women with a current or recent diagnosis of chlamydia. SETTING: A family planning clinic and a genitourinary medicine clinic in Glasgow. RESULTS: Three themes were identified: perceptions of stigma associated with sexually transmitted infection, uncertainty about reproductive health after diagnosis, and anxieties regarding partner's reaction to diagnosis. Most women had not previously perceived sexually transmitted infections as personally relevant; this was a function of stereotypical beliefs about who was "at risk" of sexually transmitted infection. These beliefs were pervasive and negatively affected reactions to diagnosis and produced anxiety about disclosure of the condition to others (particularly sexual partners) and future reproductive morbidity. This anxiety, given the uncertain natural history of chlamydia, may prove difficult to dispel. CONCLUSIONS: There are three primary areas of concern for women after a diagnosis of chlamydia which need to be examined in the proposed screening programme. Information provided should normalise and destigmatise chlamydial infection and positively promote genitourinary medicine services. Support services should be available because notification of partner can cause anxiety. Uncertainty about future reproductive morbidity may be inevitable; staff providing screening will require guidance in providing advice under such conditions.

Adult↗

Coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and prevalence of infection in the United Kingdom general population: cross sectional study.

OBJECTIVE: To measure the coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and the prevalence of infection in the general population in the United Kingdom. To investigate factors associated with these measures. DESIGN: Cross sectional survey of people randomly selected from general practice registers. Invitation to provide a specimen collected at home. SETTING: England. PARTICIPANTS: 19,773 men and women aged 16-39 years invited to participate in screening. MAIN OUTCOME MEASURES: Coverage and uptake of screening; prevalence of chlamydia. RESULTS: Coverage of chlamydia screening was 73% and was lower in areas with a higher proportion of non-white residents. Uptake in 16-24 year olds was 31.5% and was lower in men, younger adults, and practices in disadvantaged areas. Overall prevalence of chlamydia was 2.8% (95%confidence interval 2.2% to 3.4%) in men and 3.6% (3.1% to 4.9%) in women, but it was higher in people younger than 25 years (men 5.1%; 4.0% to 6.3%; women 6.2%; 5.2% to 7.8%). Prevalence was higher in the subgroup of younger women who were harder to engage in screening. The strongest determinant of chlamydial infection was having one or more new sexual partners in the past year. CONCLUSIONS: Postal chlamydia screening was feasible, but coverage was incomplete and uptake was modest. Lower coverage of postal screening in areas with more non-white residents along with poorer uptake in more deprived areas and among women at higher risk of infection could mean that screening leads to wider inequalities in sexual health.

Adolescent↗

Polymorph count for predicting non-gonococcal urethral infection: a model using Chlamydia trachomatis diagnosed by ligase chain reaction.

BACKGROUND/OBJECTIVES: The criteria for the diagnosis of non-gonococcal urethritis (NGU) on a Gram stained urethral smear are derived from previous studies which used culture as a diagnostic test for Chlamydia trachomatis. Our objectives were (1). to re-assess the relation between urethral polymorph count and C trachomatis infection, using ligase chain reaction (LCR) as the diagnostic test; and (2). to assess other possible predictors of C trachomatis infection such as symptoms, signs, demographic and behavioural variables. METHODS: We collected data from 363 men consecutively attending a genitourinary medicine clinic (excluding those with gonorrhoea and follow up visits) who had a urethral smear and a urethral LCR test for C trachomatis. The sensitivity and specificity of a discrete cut off in urethral polymorphonuclear leucocyte (PMNL) count as a diagnostic test for chlamydia urethritis were calculated. The associations between other variables, such as age and symptoms, and this infection were also estimated. RESULTS: 8% of men had C trachomatis infection and 26% of men had a PMNL count of 5 or more. Of those men with chlamydia 37% did not have NGU; 20% of men with NGU had chlamydia. Adjusted odds ratios for risk of chlamydial infection were significant for age less than 30 relative to 40 years and over (adj OR 13.6; 95% confidence interval 1.69 to 110), a PMNL count of 20 or more (6.56; 2.15 to 20.0), a PMNL count of 5-19 (3.59; 1.41 to 9.15), and the symptom of dysuria (3.27; 1.32 to 8.08). However a PMNL count of 5 or more was only 63% sensitive and 77% specific for C trachomatis infection. No association between sexual behaviour and chlamydial infection was found in this setting. CONCLUSIONS: The PMNL count is associated with presence of chlamydial infection but a large proportion of men with chlamydia have PMNL counts below the recommended cut off for a diagnosis of NSU. Lower age and the presence of symptoms may be as predictive as the urethral polymorph count for chlamydial urethritis and possibly for other urethral infections.

Adolescent↗

Chlamydia trachomatis prevalence in men in the mid-west of Ireland.

OBJECTIVES: To estimate the prevalence of chlamydia infection in young men in the Mid-Western Health Board Region of Ireland, and to determine risk factors for its acquisition. METHODS: Consecutive men attending orthopaedic clinics (OPD), and a university sports arena (UL) were recruited to a chlamydia prevalence study. All men aged 17-35 who had been sexually active and had not passed urine in the last hour were eligible. Information about chlamydia was given, informed consent obtained, and a self administered questionnaire was completed. A first void urine (FVU) was collected and tested by ligase chain reaction (LCR). RESULTS: 82% (207/252) of men from OPD, and 60% (186/310) from UL participated. 6.3% (13/207) from the OPD and 5.4% (10/186) from UL tested LCR positive, giving an overall prevalence of 5.9% (23/393). Proved risk factors for chlamydial positivity were: (1) more than one sexual partner in previous 6 months, (2) more than eight lifetime sexual partners, (3) current symptoms (dysuria or discharge). No statistical significance was found for age, condom use, smoking, days since last sexual intercourse and previous GUM clinic attendance. No statistically significant difference to cost effective prevalence of 6% was shown. CONCLUSIONS: A 5.9% prevalence of Chlamydia trachomatis was found which is cost effective to screen and treat. Non-invasive screening of men in the community was possible. Numbers of sexual partners and current symptoms were significant risk factors. Since only 25% of men in this laboratory were diagnosed with chlamydia outside the GUM clinic, compared with 59% of women, it is important that community screening of men is promoted.

Adolescent↗

Prevalence of urogenital Chlamydia trachomatis increases significantly with level of urbanisation and suggests targeted screening approaches: results from the first national population based study in the Netherlands.

OBJECTIVES: Chlamydia trachomatis (Chlamydia) is the most prevalent sexually transmitted bacterial infection and can cause considerable reproductive morbidity in women. Chlamydia screening programmes have been considered but policy recommendations are hampered by the lack of population based data. This paper describes the prevalence of Chlamydia in 15-29 year old women and men in rural and urban areas, as determined through systematic population based screening organised by the Municipal Public Health Services (MHS), and discusses the implications of this screening strategy for routine implementation. METHODS: Stratified national probability survey according to "area address density" (AAD). 21 000 randomly selected women and men in four regions, aged 15-29 years received a home sampling kit. Urine samples were returned by mail and tested by polymerase chain reaction (PCR). Treatment was via the general practitioner, STI clinic, or MHS clinic. RESULTS: 41% (8383) responded by sending in urine and questionnaire. 11% (2227) returned a refusal card. Non-responders included both higher and lower risk categories. Chlamydia prevalence was significantly lower in rural areas (0.6%, 95% CI 0.1 to 1.1) compared with very highly urbanised areas (3.2%, 95% CI 2.4 to 4.0). Overall prevalence was 2.0% (95% CI 1.7 to 2.3): 2.5% (95% CI 2.0 to 3.0%) in women and 1.5% (95% CI 1.1 to 1.8) in men. Of all cases 91% were treated. Infection was associated with degree of urbanisation, ethnicity, number of sex partners, and symptoms. CONCLUSION: This large, population based study found very low prevalence in rural populations, suggesting that nationwide systematic screening is not indicated in the Netherlands and that targeted approaches are a better option. Further analysis of risk profiles will contribute to determine how selective screening can be done.

Adolescent↗

Finding, confirming, and managing gonorrhoea in a population screened for chlamydia using the Gen-Probe Aptima Combo2 assay.

OBJECTIVES: To identify the prevalence of Neisseria gonorrhoeae (NG) within a population screened for Chlamydia trachomatis (CT). To monitor confirmatory microscopy, culture, and partner findings following reactive Aptima Combo2 assay (AC2) gonorrhoea screening tests. METHODS: Between June and December 2004, all gonorrhoea screening tests performed using AC2 for clients taking part in the Liverpool Chlamydia Screening Programme were monitored. Clients with AC2 NG reactive results were referred to a local genitourinary medicine (GUM) department for confirmatory microscopy, culture, treatment, and partner follow up. RESULTS: 47 (1%) of 4680 women and eight (1.7%) of 473 men had AC2 reactive gonorrhoea screening tests. Of those clients who agreed to follow up and were tested before any treatment, supportive evidence for a gonorrhoea diagnosis was found in 37 (97%) of 38 women and all five men. In the population opportunistically screened for chlamydia, CT prevalence rates were 12% for women and 15.7% for men. Although both women and men showed a higher relative risk for NG if chlamydia positive, of the 47 women who were reactive for NG by AC2, 55% (26) were negative for chlamydia. CONCLUSIONS: Sexually transmitted infections are rising in England and reduction of gonorrhoea rates is an objective of the Department of Health Sexual Health and HIV Strategy. AC2 tests provide an acceptable and accurate means of testing for gonorrhoea in an asymptomatic population in the community. AC2 had a higher positive predictive value than might be suggested by previous clinical trials in this low prevalence population. Although antibiotic sensitivity must be monitored, AC2 testing may offer a more acceptable alternative to microscopy and culture for NG in some populations.

Adolescent↗

The case for further treatment studies of uncomplicated genital Chlamydia trachomatis infection.

Azithromycin 1 g immediately and doxycycline 100 mg twice daily have good antimicrobial activity against Chlamydia trachomatis and treatment studies have demonstrated a >95% microbiological cure at 2-5 weeks, with antimicrobial resistance being rarely reported. Recently an 8% (95%, CI 5% to 11%) failure rate was observed in 289 women, but not in men, who had been sexually inactive after treatment. At high multiplicities of infection (load) in vitro persistence can often be demonstrated to antimicrobials-heterotypic resistance. The subsequently recovered isolates do not possess antimicrobial resistance at low loads. It is known that genital chlamydia load varies in vivo and is probably greater in women than men. In mass treatment trials of trachoma, treatment failure is associated with high chlamydia loads. It is therefore possible that women with high chlamydia loads may be at increased risk of treatment failure. Given the imminent role out of the National Chlamydia Screening Programme and the consequences of persistent chlamydial infection in women this hypothesis urgently merits further investigation.

Anti-Bacterial Agents↗