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TestPack Chlamydia, a new rapid assay for the direct detection of Chlamydia trachomatis.

TestPack Chlamydia (Abbott Laboratories) is a rapid enzyme immunoassay for the direct antigen detection of Chlamydia trachomatis in endocervical specimens. The assay is self-contained, requires no specialized equipment, and yields results in less than 30 min. The clinical performance of TestPack Chlamydia versus chlamydial cell culture was evaluated with a total of 1,694 paired endocervical specimens. Discordant samples were further investigated by immunofluorescent staining and by Chlamydiazyme immunoassay, with confirmatory procedures. The sensitivity of TestPack Chlamydia with less-than-48-h-old specimens was 76.5%, while culture sensitivity was 86.7%. TestPack Chlamydia specificity was determined to be 99.5%. These results indicate that TestPack Chlamydia is an accurate test for chlamydial infection, with a positive predictive value of 96.2%. This assay is suitable for low-volume chlamydial testing in physician offices, clinics, and smaller laboratories.

Antigens, Bacterial↗

Epidemiology and therapy of Chlamydia trachomatis infections.

Chlamydia trachomatis infections are exceedingly prevalent, and can be associated with significant sequelae. The major infections are urethritis, cervicitis, salpingitis, and ocular infection. Chlamydial genital infections present as syndromes, where C. trachomatis is one of the causes of the syndrome. Because specific laboratory diagnosis of a chlamydial infection is often not available, and even if available does not exclude the concurrent presence of other pathogens, therapy should usually be directed at all the major causes of the syndrome. Thus, although C. trachomatis is readily eradicated by tetracyclines, macrolides, sulphonamides, and rifampicin, for most situations tetracyclines are the drugs of choice. Penicillins have some activity when used in multiple-dose therapy, but are not reliable for eradication of chlamydiae. Aminoglycosides, nitroimidazoles, and the newer cephalosporins have minimal or no useful activity. Seven days of tetracycline hydrochloride 500mg 4 times daily or doxycycline 100mg twice daily are the optimum regimens for uncomplicated urethritis, cervicitis (except in pregnancy), and gonorrhoea. These regimens should be extended to 10 days for epididymitis and salpingitis. Additional antimicrobials should be added to the salpingitis regimen. For chlamydial infection during pregnancy, erythromycin 500mg 4 times daily for 1 week or 250mg 4 times daily for 2 weeks should be utilised. Neonatal infection requires 2 to 3 weeks of systemic treatment with erythromycin. Inclusion conjunctivitis responds well to antimicrobials, but improved sanitation has a greater effect than antimicrobial therapy in the management of trachoma.

Adult↗

Glycogen assay for diagnosis of female genital Chlamydia trachomatis infection.

Chlamydia trachomatis can synthesize glycogen at various stages in its developmental cycle. The glycogen content of female genital epithelial cells was detected by anthrone, and the results were compared with those from PCR. A total of 320 cervical samples were examined. Of 92 specimens that were positive by PCR, 78 were positive and 14 were negative by the glycogen assay. Of 228 specimens that were negative by PCR, 220 were negative and 8 were positive by the glycogen assay. The sensitivity and specificity of the glycogen assay obtained from these data were 84.8% (78 of 92) and 96.5% (220 of 228), respectively. Use of the glycogen assay to detect the glycogen content in genital epithelial cells may be helpful in the diagnosis of C. trachomatis infection. This is an easy, fast, and inexpensive assay and can be done in less-sophisticated labs.

Cervix Uteri↗

Oral erythromycin prophylaxis vs watchful waiting in caring for newborns exposed to Chlamydia trachomatis.

BACKGROUND: Chlamydia trachomatis exposure at birth may cause conjunctivitis or pneumonia. Until recently, a course of oral erythromycin prophylaxis was recommended for C trachomatis-exposed neonates. However, recognition of an association between erythromycin and pyloric stenosis prompted a change to a watchful waiting recommendation under which only infants who develop symptomatic C trachomatis infection are treated with oral erythromycin. OBJECTIVE: To compare erythromycin prophylaxis with watchful waiting for a hypothetical cohort of 100 000 neonates exposed to C trachomatis. METHODS: In a decision tree, potential outcomes were C trachomatis conjunctivitis, C trachomatis pneumonia (which could require inpatient or outpatient therapy), no clinical disease, and pyloric stenosis. Published data were reviewed to derive probability point estimates and ranges. Estimated charges served as outcome measures. RESULTS: Watchful waiting is less expensive than erythromycin prophylaxis ($15.1 million vs $28.3 million); prophylaxis prevents 5986 cases of C trachomatis pneumonia, including 1197 hospital admissions, but causes 3284 pyloric stenosis cases. (For every 30 infants given oral erythromycin prophylaxis, one additional case of pyloric stenosis would be expected to occur, and approximately 1.8 cases of C trachomatis pneumonia would be prevented.) In sensitivity analyses, if more than 3.4% of exposed neonates are hospitalized for C trachomatis pneumonia, prophylaxis becomes favored. CONCLUSIONS: This study supports the watchful waiting recommendation for asymptomatic C trachomatis-exposed neonates. However, there are wide plausible ranges for pyloric stenosis risk after erythromycin administration and for the incidence of C trachomatis pneumonia severe enough to require hospitalization; under some combinations of these rates, prophylaxis could be favored.

Anti-Bacterial Agents↗

Human immune response and Chlamydia trachomatis infection.

Chlamydia trachomatis is a prevalent pathogen in human populations in both developing and developed areas of the globe. Disease burden is heavy, since both acute and chronic complications can arise from infection. Emerging knowledge of the immune response to infection suggests that many of the complications of chlamydial infection are accompanied by important alterations in immunoregulation; new information suggests that both antibody-mediated and cell-mediated immune effectors may be significant in eliminating or limiting chlamydial infection. Further studies of the pathophysiologic mechanisms of host defense and the ways in which C. trachomatis escapes these defenses are needed. Elucidation of the immune response may provide the information necessary to redevelop a vaccine approach to disease control.

Antibodies, Bacterial↗

Comparative efficacy of clindamycin versus erythromycin in eradication of antenatal Chlamydia trachomatis.

Antenatal Chlamydia trachomatis infections are associated with both maternal and neonatal morbidity. Erythromycin, the only drug recommended for treatment during pregnancy, is often poorly tolerated, thus preventing successful cure. We have done a prospective, randomized, double-blind, placebo-controlled trial to compare the efficacy of clindamycin with that of erythromycin base in eradication of antenatal chlamydia. A total of 126 patients with documented cervical infection were enrolled before 24 weeks' gestation to receive clindamycin (450 mg), erythromycin (333 mg), or placebo orally four times daily for 14 days. Partners received doxycycline, 100 mg, twice daily for 7 days. Both clindamycin and erythromycin were effective agents with cure rates of 92.7% and 83.8%, respectively. Erythromycin therapy was associated with significantly more gastrointestinal complaints than was placebo therapy (23.1% (9/39) vs. 2.4% (1/41), p less than 0.02) whereas clindamycin was not. Patients who experienced side effects were more likely to be poorly compliant (p less than 0.03) and patients with moderate-to-good compliance were more likely to be cured than were women who were poorly compliant (p less than 0.002). Results of test of cure cultures performed immediately on completion of therapy did not differ significantly from those taken 4 weeks later.

Administration, Oral↗

In situ studies on incorporation of nucleic acid precursors into Chlamydia trachomatis DNA.

Chlamydiae are obligate intracellular bacteria that are dependent on eukaryotic host cells for ribonucleoside triphosphates. The purpose of the present study was to determine whether Chlamydia trachomatis obtains deoxyribonucleotides from the host cell. The study was aided by the finding that host and parasite DNA synthesis activity could be distinguished by their differing sensitivities to aphidicolin and norfloxacin. Results from isotope incorporation experiments indicated that any nucleobase or ribonucleoside that could serve as a precursor for host DNA synthesis could also be utilized by C. trachomatis for DNA replication. C. trachomatis utilized only those precursors which the host cell converted to the nucleotide level. Pyrimidine deoxyribonucleotides were efficient precursors for host DNA synthesis; however, they were not used by C. trachomatis. On the other hand, purine deoxyribonucleosides are rapidly catabolized by host cells, it is necessary to regulate their metabolism to determine whether they serve as direct precursors for C. trachomatis DNA synthesis. This was partially achieved by using a hypoxanthine-guanine phosphoribosyltransferase-negative cell line and using deoxycoformycin and 8-aminoguanosine as inhibitors of (deoxy)adenosine deaminase and purine nucleoside phosphorylase, respectively. The results indicated that purine deoxyribonucleosides are efficiently utilized for host cell DNA synthesis even if degradation pathways are inhibited and salvage to ribonucleotides is minimized. In sharp contrast, the purine deoxyribonucleosides were utilized by C. trachomatis as precursors for DNA synthesis only when host catabolic pathways and salvage reactions were intact. High-pressure liquid chromatographic analysis of nucleotide pools extracted from host cells pulsed with radiolabeled precursors suggests that infected cells transport and phosphorylate all deoxynucleosides as effectively as mock-infected control cultures. In aggregate, these results show that chlamydiae do not take up deoxyribonucleotides from the host cells.

Animals↗

Intra-amniotic Chlamydia trachomatis infection.

Chlamydia trachomatis is one of the most prevalent genital pathogens in pregnant women. Ascending, transcervical infection may reach fetal membranes creating chorioamnionitis or amniotic fluid infection. The aim of this study was to examine amniotic fluids obtained during cesarean section for the presence of chlamydial IgM- and IgG-specific antibodies, and for the presence of C. trachomatis antigen. Five of 52 (9.6%) amniotic fluid samples were seropositive. Two of 52 (3.8%) amniotic fluid samples had C. trachomatis antigen in the epithelial cells of the amnion. In conclusion, our data indicate that there is a high rate of transmission of C. trachomatis from mother to infant and that the pathogen can be identified in the amniotic fluid.

Adolescent↗

Prediction of efficacy of antimicrobial agents in treatment of infections due to Chlamydia trachomatis.

Although Chlamydia trachomatis is readily eradicated by systemic therapy in patients with acute urethritis, systemic therapy is less satisfactory in treatment of chronic trachoma. The activities of antimicrobial agents against C. trachomatis in cell cultures when the antimicrobial agents are added 1 hr after the C. trachomatis (minimal inhibitory concentration [MIC]) predicts efficacy of the drugs in the treatment of urethritis but does not necessarily predict efficacy in the treatment of chronic ocular trachoma. Concentrations of antimicrobial agents required to eradicate C. trachomatis when the agents were added 48 hr after inoculation of the cell cultures with C. trachomatis exceeded the MIC by several logarithms, and minocycline, doxycycline, and rifampin were markedly more active than tetracycline, erythromycin, or several other antimicrobial agents. Of the three most active antimicrobial agents, only doxycycline has been used systemically to treat ocular infections due to C. trachomatis, and it has been reported to be the most effective antimicrobial agent that has been utilized. In vitro testing of obligate intracellular pathogens such as C. trachomatis presents unique problems. Utilization of several methods of testing may help to identify antimicrobial agents with improved clinical efficacy, particularly in the treatment of ocular trachoma.

Anti-Bacterial Agents↗

Modern diagnosis and management of genital Chlamydia trachomatis infection.

Chlamydia trachomatis infection is now the commonest bacterial, sexually transmitted infection in the UK. Uncomplicated genital chlamydial infection often does not produce symptoms in men or women, but patients may present with sequelae. New diagnostic techniques are available to identify C. trachomatis more easily and new antibiotic regimens provide effective treatment. These factors, together with heightened awareness within the medical profession and the general population, should help to reduce the prevalence of this infection.

Anti-Bacterial Agents↗

In-vitro activity of roxithromycin against Chlamydia trachomatis.

Ten Chlamydia trachomatis isolates were tested for their sensitivity to roxithromycin, in comparison with erythromycin and tetracycline. The minimum inhibitory and minimum bactericidal concentrations of roxithromycin ranged from 0.03-0.12 and 0.25-1 microg/ml, respectively.

Anti-Bacterial Agents↗

Relative resistance to erythromycin in Chlamydia trachomatis.

Recent Chlamydia trachomatis isolates were tested in a tissue culture system for susceptibility to tetracycline, erythromycin, rosaramicin, rifampin, and clindamycin. Rifampin was the most active drug (minimal inhibitory concentration, less than or equal to 0.02 microgram/ml). Tetracycline and rasaramicin were highly active, with a concentration of less than or equal to 0.25 microgram/ml being chlamydicidal. Clindamycin was least active on a weight basis, requiring up to 16 microgram/ml to prevent the passage of chlamydiae into a drug-free tissue culture system. Relative resistance to erythromycin was detected; two isolates were capable of limited replication in 1 microgram/ml.

Anti-Bacterial Agents↗

Oral immunization with an anti-idiotypic antibody to the exoglycolipid antigen protects against experimental Chlamydia trachomatis infection.

Chlamydia trachomatis is the leading cause worldwide of preventable infectious blindness (trachoma) and sexually transmitted disease, including nongonoccocal urethritis and pelvic inflammatory disease. To date, no effective vaccine against C. trachomatis infection has been identified. A monoclonal anti-idiotypic antibody (anti-Id) to the chlamydial exoglycolipid antigen (GLXA) was tested in a murine model of ocular chlamydial infection for its ability to induce systemic immunity, which reduces microbiologic and clinical disease. The anti-Id to GLXA, delivered either systemically in soluble form or orally after encapsulation in poly(lactide) microspheres, induced significant protective immunity against ocular challenge of mice with a human biovar of C. trachomatis. Protection was associated with induction of anti-GLXA antibody and anti-chlamydial neutralizing antibody.

Administration, Oral↗

Intra-articular co-infection by Borrelia burgdorferi and Chlamydia trachomatis.

OBJECTIVE: Chlamydia trachomatis and Borrelia burgdorferi infections are frequently the cause of unexplained oligoarthritis, as shown by identification of bacteria specific DNA in joint material from patients with reactive arthritis, Lyme arthritis, and undifferentiated oligoarthritis. The aim of this study was to determine whether the two organisms occur simultaneously in joint material from patients with arthritis. METHODS: Seventy six patients with unexplained arthritis were prospectively studied. Synovial fluid was obtained from all patients and examined for DNA from C trachomatis and B burgdorferi using specific polymerase chain reaction (PCR) protocols. Data concerning prior genitourinary infection or a history of tick bite were recorded and serum antibodies to C trachomatis and B burgdorferi were determined. RESULTS: Six patients (8%) had DNA from both C trachomatis and B burgdorferi in the same synovial fluid specimen (mean leucocyte count 11.925/mm(3), 65% granulocytes). These patients (four men, two women; mean age 33.7 years) all had oligoarthritis of the knee, ankle, or both (mean disease duration 11.3 months). From the history and serological examination, four patients had some evidence of actual or previous infection with one or other of the bacteria, while the other two patients had a positive serological test for Chlamydia only. CONCLUSIONS: DNA from two different microorganisms which are known to be triggering agents for arthritis may be present simultaneously in joint material from patients with unexplained oligoarthritis. This finding raises the question as to whether, in such cases, one or both bacteria contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

Adult↗

[Modern diagnosis of Chlamydia trachomatis infections].

Chlamydia trachomatis is the most frequent sexually transmitted bacterial infection. Tests to diagnose C. trachomatis infections include growth on cell culture and assays detecting bacterial antigens or nucleic acids. Until recently, culture was considered the gold standard of testing because of its high specificity. However, the sensitivity of culture is limited. Nucleic acid amplification tests (NATs) have the highest sensitivity and are almost as specific as culture. They are best suited for screening. Chlamydial antigen EIAs are considerably less sensitive and specific, resulting in low positive predictive values, especially when low-prevalence populations are studied. Thus, positive results of chlamydia antigen EIAs should be confirmed by another test.

Bacterial Typing Techniques↗

Management of genital Chlamydia trachomatis infections.

Chlamydia trachomatis is a common cause of genital infection and can give rise to urethritis and epididymitis in men and cervicitis and pelvic inflammatory disease in women. However, most genital chlamydial infections do not produce symptoms and so may be spread unknowingly. This article discusses the diagnosis and treatment of infection and how the risk of spread may be reduced.

Anti-Bacterial Agents↗

Evaluation of a novel solid-phase immunoassay, Clearview Chlamydia, for the rapid detection of Chlamydia trachomatis.

Clearview Chlamydia (Unipath Limited, Bedford, United Kingdom) is a rapid immunoassay for the direct detection of Chlamydia trachomatis antigen. This assay was evaluated against the tissue culture method by using 376 paired endocervical specimens. The Clearview assay had a sensitivity of 93.5% and a specificity of 99% when it was compared with the tissue culture method. This assay does not require specialized equipment or trained personnel and yields results within 30 min from the time that a specimen is collected.

Bacteriological Techniques↗