Repeated Chlamydia trachomatis infections are associated with lower bacterial loads.

Chlamydia trachomatis (CT) infections remain highly prevalent. CT reinfection occurs frequently within months after treatment, likely contributing to sustaining the high CT infection prevalence. Sparse studies have suggested CT reinfection is associated with a lower organism load, but it is unclear whether CT load at the time of treatment influences CT reinfection risk. In this study, women presenting for treatment of a positive CT screening test were enrolled, treated and returned for 3- and 6-month follow-up visits. CT organism loads were quantified at each visit. We evaluated for an association of CT bacterial load at initial infection with reinfection risk and investigated factors influencing the CT load at baseline and follow-up in those with CT reinfection. We found no association of initial CT load with reinfection risk. We found a significant decrease in the median log10 CT load from baseline to follow-up in those with reinfection (5.6 CT/ml vs. 4.5 CT/ml; P = 0.015). Upon stratification of reinfected subjects based upon presence or absence of a history of CT infections prior to their infection at the baseline visit, we found a significant decline in the CT load from baseline to follow-up (5.7 CT/ml vs. 4.3 CT/ml; P = 0.021) exclusively in patients with a history of CT infections prior to our study. Our findings suggest repeated CT infections may lead to possible development of partial immunity against CT.

Chlamydia trachomatis IgG3 seropositivity is associated with gastroschisis.

OBJECTIVE: To investigate the association between Chlamydia trachomatis (CT) infection seropositivity and gastroschisis. STUDY DESIGN: In this case-control study we enrolled pregnant women either prenatally diagnosed with gastroschisis (cases, n=33) or with a normal ultrasound (controls, n=66). Both groups attended the University of Utah's Maternal Fetal Medicine Diagnostic Center for their diagnostic ultrasound or because of a community obstetrician referral. Participants completed a structured interview on potential risk factors. Anti-CT immunoglobulin (IgG)1 and IgG3 were measured by a CT elementary body enzyme-linked immunosorbent assay. RESULT: Median age at sexual debut was lower and reported sexual partner number higher in cases compared with controls. Risk factors for gastroschisis included having ⩾ 3 sexual partners (odds ratio (OR)=3.3, 95% CI 1.2, 9.4), change in partner from the previous pregnancy (OR=3.6, 95% CI 0.9, 13.9) and anti-CT IgG3 seropositivity (age-adjusted OR=3.9, 95% CI: 1.1, 13.2). CONCLUSION: Anti-CT IgG3 seropositivity was associated with greater than a threefold risk for gastroschisis.

Chlamydia trachomatis OmpA genotyping as a tool for studying the natural history of genital chlamydial infection.

OBJECTIVE: To investigate the relationship of Chlamydia trachomatis (CT) outer membrane protein A (OmpA) type to the clearance of CT infection before treatment. METHODS: CT OmpA genotyping, with amplification and sequencing of ompA, was utilised to study the natural history of CT infection (spontaneous resolution vs persistence) in 102 individuals with chlamydia-positive screening tests returning for treatment. RESULTS: CT OmpA distribution was associated with spontaneous resolution of CT, most notably with CT OmpA genotype J/Ja detected more often from the initial screening CT test than other genotypes in those who then had spontaneous resolution of CT noted at the time of treatment. Five individuals with presumed persisting CT infection had discordant CT OmpA genotypes at the screening and treatment visits, suggesting possible new interval CT infection. CONCLUSIONS: Clearance of chlamydia by the host before treatment may be influenced by the CT OmpA genotype infecting the host. CT OmpA genotyping may be a valuable tool in understanding the natural history of chlamydial infections.

Interleukin (IL)-2 and IL-12 responses to Chlamydia trachomatis infection in adolescents.

Chlamydia trachomatis infects epithelial cells at the mucosal surface. While in vitro and animal studies have shown changes in mucosal T(H)1-associated cytokines in the presence of C. trachomatis infection and with its progression to the upper genital tract or clearance, in vivo cytokine responses to chlamydial infection in humans are not well understood. Using a quantitative enzyme-linked immunosorbent assay (ELISA), we examined the endocervical production of two T(H)1-associated cytokines, i.e. interleukin (IL)-2 and IL-12, in relation to C. trachomatis infection in adolescents. At a randomly selected visit for 396 females, median endocervical IL-2 levels were significantly lower (190 versus 283 pg/ml, P = 0.02) and median IL-12 levels significantly higher (307 versus 132 pg/ml, P < 0.001) in subjects testing positive versus negative for C. trachomatis. These divergent T(H)1-associated cytokine responses were: (1) confirmed in paired analyses of 96 individuals before and after infection within 6-month intervals, (2) reversible in 97 patients who cleared infection during consecutive visits, (3) not attributable to sociodemographic factors or other genital infections and (4) independent of common genetic variants at the IL2 and IL12B loci associated previously with differential gene expression. From these findings we infer that increased IL-12 and decreased IL-2, observed commonly during mucosal inflammation, are important features of mucosal immune defence against C. trachomatis infection.

Phenytoin hypersensitivity syndrome masquerading as fever and systemic illness of unknown origin in an HIV-infected patient.

A 32-year-old HIV-infected woman developed fever and systemic illness of unknown origin after being placed on phenytoin for seizures. Her clinical syndrome, skin biopsy findings, and clinical response to steroids were consistent with phenytoin hypersensitivity syndrome.

Vaginal leucocyte counts in women with bacterial vaginosis: relation to vaginal and cervical infections.

OBJECTIVES: To evaluate whether an elevated vaginal leucocyte count in women with bacterial vaginosis (BV) predicts the presence of vaginal or cervical infections, and to assess the relation of vaginal WBC counts to clinical manifestations. METHODS: We retrospectively analysed the relation of vaginal leucocyte counts to vaginal and cervical infections and to clinical manifestations in non-pregnant women diagnosed with BV at an STD clinic visit. RESULTS: Of 296 women with BV studied, the median age was 24 years and 81% were African-American. Elevated vaginal leucocyte counts were associated with objective signs of vaginitis and cervicitis and also predicted candidiasis (OR 7.9, 95% CI 2.2 to 28.9), chlamydia (OR 3.1, 95% CI 1.4 to 6.7), gonorrhoea (OR 2.7, 95% CI 1.3 to 5.4), or trichomoniasis (OR 3.4, 95% CI 1.6 to 7.3). In general, as a screening test for vaginal or cervical infections, vaginal leucocyte count had moderate sensitivities and specificities, low positive predictive values, and high negative predictive values. CONCLUSIONS: An elevated vaginal leucocyte count in women with BV was a strong predictor of vaginal or cervical infections. Vaginal leucocyte quantification may provide an alternative approach to assessing need for empirical therapy for chlamydia and gonorrhoea, particularly in resource-limited high STD risk settings that provide syndromic management.

Methodologies and cell lines used for antimicrobial susceptibility testing of Chlamydia spp.

In vitro susceptibility testing was performed on strains of Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci under various conditions, including the cell line utilized, the time between infection and the addition of an antimicrobial, the concentration of inoculum, and the effect of multiple passage on the minimal chlamydicidal concentrations for the antibiotics doxycycline, azithromycin, erythromycin, ofloxacin, and tetracycline. With macrolides, the MIC varied depending upon the cell line utilized. With all antimicrobials, the MIC was related to the time at which the antimicrobial was added after infection. By an optimized cell culture passage method, all strains of chlamydia tested demonstrated survival after exposure to high levels (>100 times the MIC) of antimicrobials. Furthermore, upon retest, these surviving organisms did not demonstrate increased MICs. Thus, this phenomenon does not reflect selection of antimicrobial-resistant mutants but rather survival of some organisms in high antimicrobial concentrations (heterotypic survival). An additional 44 clinical isolates of C. trachomatis from patients with single-incident infections were tested against those from patients with recurrent or persistent infections, and heterotypic survival was seen in all isolates tested; hence, in vitro resistance did not correlate with the patient's apparent clinical outcome.

Quantitative culture of Chlamydia trachomatis: relationship of inclusion-forming units produced in culture to clinical manifestations and acute inflammation in urogenital disease.

The relationship of Chlamydia trachomatis inclusion-forming units in quantitative culture to clinical manifestations and inflammation in urogenital disease was assessed in 1179 patients attending a sexually transmitted diseases clinic. In women, greater inclusion-forming unit counts were associated with cervical mucopus (3000 vs. 450 ifu), amount and character of cervical discharge, > or =30 polymorphonuclear cells (PMNL) per high-power field (hpf) on Gram stain (2050 vs. 320 ifu), and diagnoses of mucopurulent cervicitis (MPC; 2550 vs. 300 ifu) and pelvic inflammatory disease (PID; 3000 vs. 578 ifu). In men, greater inclusion-forming unit counts were associated with urethral discharge (85 vs. 44 ifu), amount and character of discharge, and > or =10 PMNL/hpf (95 vs. 50 ifu). These associations persisted on multivariate analysis. Thus, chlamydial replication is associated with MPC and PID in women, urethritis in men, and inflammation in both. Since infections with high inclusion counts may be the most transmissible, identification and treatment of patients with these chlamydia-associated syndromes is important in control programs.

Epidemiology and clinical manifestations of unique Chlamydia trachomatis isolates that occupy nonfusogenic inclusions.

Unique Chlamydia trachomatis strains characterized by multiple nonfusing inclusions were recently described. These strains lack evidence of the protein IncA in the inclusion membrane and have mutations in the incA gene. This study evaluated the epidemiology and clinical manifestations of patients infected with nonfusing mutant strains (case patients) and compared them with patients infected with wild-type fusing strains (control subjects). Both male and female case patients had fewer signs of infection than did control subjects (P=.016 and P=.019, respectively). Female case patients also had fewer symptoms of infection (P=.02). Median inclusion-forming unit (ifu) counts were lower in male and female case patients (P=.045 and P=.135, respectively). Thus, nonfusing strains of C. trachomatis more often produce subclinical infections than do normal fusing strains and have lower median ifu counts. From a prevention perspective, the data underscore the importance of screening programs to detect and treat inapparent C. trachomatis infection.

Pneumonia and sepsis due to fluoroquinolone-resistant Capnocytophaga gingivalis after autologous stem cell transplantation.

Human oral Capnocytophaga species have been only rarely described as a cause of sepsis in patients following stem cell or marrow transplantation, and pneumonia has not been reported in this setting. In addition, fluoroquinolone resistance is rarely seen in these species, and has never been reported in C. gingivalis. We report a case of pneumonia (confirmed by culture of bronchoalveolar lavage fluid) and sepsis due to fluoroquinolone- resistant Capnocytophaga gingivalis in a patient following autologous stem cell transplantation, who responded to treatment with linezolid and metronidazole. Capnocytophaga infections should be considered in patients with fever following stem cell or marrow transplantation, especially those with neutropenia and mucositis. Susceptibility testing is needed given the existence of multidrug-resistant isolates.