Screening for chlamydial infections in women attending family planning clinics.
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Biomedical subjects
Publications and source records attributed to J Schachter.
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We tested 383 women with and 500 women without cervical neoplasia for antibodies against Chlamydia trachomatis or herpes simplex virus (HSV). Exposure to both agents was related to sexual activity, with the highest prevalence of antibodies found in women with more sex partners and who had first coitus at an earlier age. When subjects were matched for several risk factors (age, race, marital status, parity, number of sex partners, and history of venereal disease), a significant excess of antibodies against C trachomatis was found in cases as compared with control subjects (76.5% v 58.4%, respectively; n = 149). Because matched-pair analysis lost a substantial proportion of women with neoplasia (largely because they were older), linear logistic analysis was performed. This also showed an excess of antichlamydial antibody in cases, with an estimated odds ratio of approximately 2 for the association of antichlamydial antibody and the risk of being a case. Neither analysis found an excess of antibodies to HSV type 2 in cases.
The lymphogranuloma venereum (LGV) L2 serotype of Chlamydia trachomatis has been isolated from the rectums of three homosexual men with acute, primary ulcerative proctitis that responded to appropriate anti-chlamydial therapy. LGV is still present in the urban United States and must be considered in cases of acute ulcerative proctitis.
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Athymic nude (nu/nu) mice, which are more susceptible to the agent of mouse pneumonitis (MoPn) (murine Chlamydia trachomatis) than are their heterozygous littermates (nu/+), do not develop significant IgG or IgA antibody to the MoPn agent. Nu/+ mice develop significant titers of both specific IgG or IgA antibodies after either intranasal or intrauterine challenge. Prior intranasal or intrauterine immunization protects nu/+ but not nu/nu mice against subsequent intranasal challenge with the MoPn agent. Resistance to pneumonia due to the MoPn agent can be transferred to nu/nu mice by nu/+ mouse immune serum (with high titers of IgG and IgA antibodies to the MoPn agent) but not by nu/+ mouse normal serum (with undetectable titers of IgG and IgA antibodies to the MoPn agent). Serum components, probably specific antibodies, are important in host defense against the MoPn agent.
Sera from 502 infants with pneumonia were tested for antibodies to Chlamydia trachomatis by the microimmunofluorescence test; 175 (34.9%) were positive for IgM antibodies (titer, greater than or equal to 1:32). Chlamydiae were recovered from 42 (46.2%) of 91 IgM antibody-positive infants as compared with six (3.3%) of 181 IgM antibody-negative infants (P less than 0.0001). Two (4%) of 46 of the infants with inclusion conjunctivitis, but not pneumonia, had titers of IgM antibody of greater than or equal to 1:32; both shed the organism from the rectum. IgM antibody to C. trachomatis is not maternally transmitted to infants and was detected at a low rate (1.1%) in infants with nonpneumonic conditions. Diagnosis of pneumonia due to Chlamydia in infants by isolation of the agent is slow and unreliable. High levels of IgM antibody (greater than 1:32) appear to reflect a systemic chlamydial infection and offer the possibility of a same-day diagnosis. Thus, the detection of specific IgM antibodies to C. trachomatis may be the method of choice in diagnosing chlamydial pneumonia in infants.
A patient with simultaneous proctitis and meningitis due to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was extensively investigated. In both disease locations the infection was clinically evident and culture-proven. Analysis by sodium dodecylsulfate-polyacrylamide gel electrophoresis of rectal isolates revealed both HSV-1 and HSV-2. The cerebrospinal fluid harbored two apparently different strains of HSV-1, one of which was shown by restriction endonuclease analysis to be identical with the rectal isolate of HSV-1.
Blood pressure (BP) was measured on the third postnatal day in 392 healthy, full-term, appropriate weight infants, and again in 318 infants at six months, in 277 infants at 15 months, and in 232 infants at 24 months of age. Differences in average BP between white infants and black infants were small; BP did not vary significantly as a function of socioeconomic class or sex. BP, measured during sleep, had increased from birth to six months of age, but showed no change from six to 15 months, a period of rapid growth, during which average weight increased 37% and average height increased 16%. BP continued to show to change from 15 to 24 months, when waking BP measurements at 24 months were adjusted for sleep-waking differences in BP. Cross-sectional and analyses revealed only modest weight-BP relationships at 15 and 24 months. Five per cent of the infants exhibited systolic BPs which remained above the 80th percentile at six, 15, and 24 months of age. This was six times the number expected by chance if BP was assumed to be uncorrelated from measurement to measurement. This group of infants showed physical maturation, measured by weight change, which was almost identical with that of the total cohort.
The major outer membrane proteins (MOMPs) of several Chlamydia trachomatis serotypes (B, D, G, H, and L2) and of the C. psittaci meningopneumonitis strain were purified by preparatory sodium dodecyl sulfate-(SDS)-polyacrylamide gel electrophoresis. The isolated SDS-polypeptide complexes, which varied in their apparent subunit molecular weights, were used as immunogens to raise hyperimmune rabbit antisera. The specificities of these antisera were determined both by rocket immunoelectrophoresis with the soluble SDS-polypeptide complex as antigen and by micro-immunofluorescence with whole organisms. By rocket immunoelectrophoresis, each of the soluble C. trachomatis MOMPs was immunologically related; however, no immunological cross-reactions occurred with the C. psittaci meningopneumonitis polypeptide, indicating that the MOMPs are antigenically distinct among members of these two chlamydial species. The same antisera were highly reactive with intact organisms by micro-immunfluorescence, demonstrating that at least some of the antibodies raised with SDS-polypeptide complexes reacted with native antigenic sites of these surface proteins. By micro-immunofluorescence, anti-MOMP sera remained species specific; but, unlike the results observed by rocket immunoelectrophoresis, distinct differences in the reactivity and specificity of these antisera were observed among C. trachomatis serotypes. C. trachomatis isolates were separated into two distinct serogroups on the basis of their reactivity with anti-MOMP sera. B complex organisms (B, Ba, D, E, F, G, K, L1, L2, and L3) all reacted strongly with anti-MOMP sera of the B, D, G, and L2 serotypes. In contrast, these same antisera were poorly reactive with the C complex serotypes A, C, H, I, and J. Anti-H MOMP serum was the most serospecific, since high-antibody titers were found only against the homologous H serotype organism. These findings indicate that MOMPs of different strains of C. trachomatis are antigenically complex and that antigenic heterogeneity exists among the surface-exposed portions of the protein.
Chlamydia trachomatis (strains L2 and DE) were found to infect fertilized mouse ova in vitro. Inclusions were found in the trophoblast, but not in the embryo.
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An animal model of chronic cicatrizing trachoma has been produced by repeated ocular inoculation with Chlamydia trachomatis serotype E, a genitally transmitted strain. We have now produced a chronic follicular conjunctivitis on cynomolgus monkeys by repeated inoculation with C. trachomatis serotype A, which has been isolated from an area of endemic trachoma. This disease was similar in all respects to that which followed infection with the serotype E strain. Cynomolgus monkeys inoculated with a single dose of serotype E of C. trachomatis strain developed an acute, self-limited follicular conjunctivitis, which was intense for 4 weeks and then slowly subsided. The organism could be reisolated only during the first 4 weeks after inoculation. On reinoculation at 15 and 30 weeks after the initial infections, these animals demonstrated only a mild and transitory clinical response, and the agent could be recovered for only up to 14 days after inoculation. In contrast, repeated weekly reinoculation with either serotype led to a chronic progressive clinical response in these animals, although after the first 6 weeks the agent was isolated only occasionally. This chronic disease was shown not to be due to hypersensitivity to the egg yolk components in which the organism was grown. These data suggest that the serotype of the chlamydial organism may not be as important in determining the clinical course of disease as is the frequency or persistence of exposure to the chlamydial agent. Although a single inoculum produced an acute follicular conjunctivitis, repeated inoculation is needed to produce the chronic disease characteristic of trachoma in this animal model.
Because topical antibiotic treatment has had a limited effect in previous controlled trials against trachoma, treatment with oral erythromycin was compared with topical tetracycline in 6-8-year-old children in southern Tunisia who had potentially blinding active trachoma. A total of 169 children were divided into two groups that were carefully matched for age, sex, locality, and intensity of disease. Oral erythromycin ethyl succinate in a paediatric dosage form was administered to one group and topical 1% tetracycline ointment to the other group, twice daily, six days a week for three weeks. The two treatments were equivalent in effectiveness and resulted in a substantial decrease in disease intensity and a marked reduction in chlamydial infection detected in conjunctival smears. To maintain blood levels of antibiotics known to be effective in the treatment of chlamydial infections with a dosage schedule possible in a trachoma control programme, one of the long-acting tetracyclines (doxycycline or minocycline) might be considered. Such systemic chemotherapy should be limited to selective treatment of individuals who can be adequately monitored.
We studied 52 adult patients admitted to the hospital over a 11-month period with symptoms suggesting pulmonary infection. Twenty-nine had pneumonia and none were receiving immunosuppressive drug therapy. We found definite serological evidence of recent chlamydial infection in 21% (4/19) of patients with pneumonia of unclear etiology, and in 0% (0/33) of patients with other pulmonary conditions. An additional three patients with pneumonia had suggestive serological evidence of recent chlamydial infection. None of the seven patients had culture evidence of bacterial infection, or serological evidence of mycoplasmal, viral, or Legionella infection; none had physical examination findings suggesting intercurrent chlamydial infection of the eye or genitourinary tract. Chlamydia trachomatis may have been a cause of community-acquired pneumonia in some of these patients.
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Athymic nude mice (nu/nu) were significantly more susceptible to pneumonia due to the agent of mouse pneumonitis (MoPn), Chlamydia trachomatis, than their heterozygous (nu/+) littermates, as judged both by a greater mortality and a decreased ability to rid their lungs of the infection. Nu/nu mice did not produce significant antibody to the MoPn agent, whereas nu/+ mice did. Thymic transplantation rendered nu/nu mice significantly more resistant to the MoPn agent than nu/nu controls. Resistance to the MoPn agent and production of specific antibody to the MoPn agent were dependent on thymus-derived cells.
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Elementary bodies (EB) of Chlamydia trachomatis serotypes C, E, and L2 were extrinsically radioiodinated, and whole-cell lysates of these serotypes were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Autoradiography of the polypeptide profiles identified a major surface protein with an apparent subunit molecular weight of 39,500 that was common to each C. trachomatis serotype. The abilities of nonionic (Triton X-100), dipolar ionic (Zwittergent TM-314), mild (sodium deoxycholate and sodium N-lauroyl sarcosine), and strongly anionic (SDS) detergents to extract this protein from intact EB of the L2 serotype were investigated by SDS-PAGE analysis of the soluble and insoluble fractions obtained after each detergent treatment. Only SDS readily extracted this protein from intact EB. Sarkosyl treatment selectively solubilized the majority of other EB proteins, leaving the 39,500-dalton protein associated with the Sarkosyl-insoluble fraction. Ultrastructural studies of the Sarkosyl-insoluble EB pellet showed it to consist of empty EB particles possessing an apparently intact outer membrane. No structural evidence for a peptidoglycan-like cell wall was found. Morphologically these chlamydial outer membrane complexes (COMC) resembled intact chlamydial EB outer membranes. The 39,500-dalton outer membrane protein was quantitatively extracted from COMC by treating them with 2% SDS at 60 degrees C. This protein accounted for 61% of the total COMC-associated protein, and its extraction resulted in a concomitant loss of the COMC membrane structure and morphology. The soluble extract obtained from SDS-treated COMC was adsorbed to a hydroxylapatite column and eluted with a linear sodium phosphate gradient. The 39,500-dalton protein was eluted from the column as a single peak at a phosphate concentration of approximately 0.3 M. The eluted protein was nearly homogeneous by SDS-PAGE and appeared free of contaminating carbohydrate, glycolipid, and nucleic acid. Hyperimmune mouse antiserum prepared against the 39,500-dalton protein from serotype L2 reacted with C. trachomatis serotypes Ba, E, D, K, L1, L2, and L3 by indirect immunofluorescence with EB but failed to react with serotypes A, B, C, F, G, H, I, and J, with the C. trachomatis mouse pneumonitis strain, or with the C. psittaci feline pneumonitis, guinea pig inclusion conjunctivitis, or 6BC strains. Thus, the 39,500-dalton major outer membrane protein is a serogroup antigen of C. trachomatis organisms.