Sulfonamides and sulfones in dermatologic therapy.
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Non-gonococcal ophthalmia neonatorum was the first recognized manifestation of sexually transmitted chlamydial infection and for many years it was thought to be the only manifestation in infants born to infected mothers. In the 20 years since techniques for isolation of Chlamydia trachomatis in cell culture were described, many important effects of chlamydial infection, including afebrile pneumonia in infants, have been established. Prospective studies have determined the incidence of chlamydial infection in pregnant women and the risk of transmission of infection to their infants. They have shown that these are among the commonest perinatal infections. It is estimated that at least 1% of infants in this community have chlamydial conjunctivitis and up to 5/1000 will develop pneumonia. Chlamydial infections are characterized by a subacute onset and, without appropriate treatment, a prolonged course. Although they are rarely fatal, symptoms are sometimes severe and there may be long-term sequelae. The recent development of rapid and relatively inexpensive methods for direct detection of chlamydiae in clinical specimens will facilitate the diagnosis and treatment of infections in infants.
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A retrospective case-control study was designed to assess risk factors for neonatal infection. Nonprivate patients (8,215) who delivered in a period from January 1, 1983 to June 30, 1988 were studied. Ninety three cases of conjunctivitis (incidence 2.4/1,000), 104 cases of pneumonia (incidence 2.8/1,000), and 50 cases of sepsis (incidence 1.3/1,000) were identified. Group B streptococcus was cultured from septic neonates in 46%. Calculated Odds ratio's indicated prematurity/low birth-weight (OR 6.9) and antepartum fetal tachycardia (OR 6.3) as important risk factors for pneumonia/sepsis. Prematurity/low birth-weight (OR 3.0) and an abnormal presentation in the birth canal (OR 2.8) were identified as risk factors for conjunctivitis. After testing all the risk factors found by univariate analysis in a logistic regression model tachycardia (chi 2 35.21, p less than 0.001) remained an independent predictor for neonatal pneumonia/sepsis and abnormal vaginal presentation (chi 2 7.58, p 0.006) for conjunctivitis.
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PROBLEM: Establishing the correlation between antichlamydial antibodies (AchAbs) and antisperm antibodies (ASA) in patients with chlamydial infections. METHOD OF STUDY: ASA were studied in sera from patients (142 with genital, 57 with ocular chlamydial infections) and control group (n = 100) by gelatin and tray agglutination test (TAT), sperm immobilization test (SIT) and ELISA. AchAbs were revealed by ELISA. RESULTS: A significantly higher (P < 0.05) ASA incidence was noted in patients with genital infections as compared with controls and patients with ophthalmologic infection (P < 0.0001), but not between patients with ophthalmologic infection and controls (P > 0.05). A significant correlation was established between AchAbs and ASA for TAT (r = 0.8214, P = 0.0341), SIT (r = 0.797, P = 0.032) and ELISA (r = 0.8519, P = 0.0313) in patients with genital infections only. CONCLUSIONS: The genital Chlamydia infection may play a role in the induction of ASA. This is probably a result of the inflammatory process, but not of cross-reactivity between sperm and Chlamydia trachomatis antigens.
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Chlamydia trachomatis (Ct) was isolated from eyes of 33 out of 160 infants with neonatal conjunctivitis. In nineteen (58%) of the infants with chlamydial conjunctivitis Ct could also be isolated from the nasopharynx. All infants were treated with oral erythromycin ethylsuccinate 25 mg/kg every 12 hours for 14 days combined with lid hygiene. All were clinically cured, and none had a relapse of clinical Ct conjunctivitis during an observation period of one year. However, one infant had persistent asymptomatic chlamydial eye infection, two displayed a persistent infection of the nasopharynx, and one infant's vagina was infected despite therapy. Serum IgG antibodies to Ct were significantly more often detected in clinical cases (90%) than in controls (33%) (p less than 0.01). Infants with conjunctivitis developed detectable IgM antibodies to Ct in 43% as compared to 7% in controls (p less than 0.01).
Tear and serum samples from 128 neonates and 122 adults with conjunctivitis were examined for antibodies to Chlamydia trachomatis with a micro-immunofluorescence (MIF) technique and the results compared to antigen detection by culture, enzyme immunoassay (EIA) (Chlamydiazyme, Abbott) and direct immunofluorescence (IF) (MicroTrak, Syva and Chlamyset, Orion) tests. From the 52 culture-positive adults, chlamydial IgA (titre greater than or equal to 1:8) antibodies were detected in 81% of the tear and in 62% of the serum samples, while 88% had such serum IgG antibodies (titre greater than or equal to 1:32). The persistence of chlamydial IgA in tears and sera was related to the duration of symptoms of conjunctivitis and the antibody titres declined after institution of antibiotic treatment. In the adults, the sensitivity of the MIF tear IgA antibody test (81%) was higher than that of the EIA (71%) and the IF (MicroTrak 71% and Chlamyset 62%) tests. The specificity for the MIF test was 79%, while it was 100% for the EIA and the two IF tests. Of the 67 chlamydia-infected neonates, 36% had chlamydial tear IgA antibodies, while such antibodies were only found in 15% of the sera. No neonates with chlamydia-negative conjunctivitis had chlamydial IgA antibodies. The MIF test may be used as a diagnostic method complementary to culture, EIA and IF tests in the diagnosis of chlamydial conjunctivitis in adults, but is not applicable in neonates.
Out of 300 newborn infants who had conjunctival swabs inoculated for detection of Chlamydia trachomatis and other bacteria, 72% had bacteria isolated 4 to 6 days after birth. Of these, Staph. albus constituted 51% and Staph. aureus 19%. None of the infants were Chlamydia positive. Five out of 112 mothers (4.5%) were Chlamydia positive from the cervix just before delivery. Nineteen of the neonates were treated for conjunctivitis within the first month of life. Chlamydia trachomatis was isolated from 2, and Staph. aureus, alpha-Streptococci, Pneumococci and Haemophilus influenzae from some of the other infants. A likely diagnosis could be made in 46% of these cases, while the remaining cultures showed only apathogenic bacteria or no growth. There was a fairly good accordance with observation of inflammatory cells in the tear fluid and the clinical picture, 17/19 = 90% showing neutrophilia. Despite failing aetiological diagnosis in several cases, the infants responded satisfactorily to local antibiotic treatment. 75% of the parents replied to questionnaires 2 months after birth concerning conjunctivitis within the first month of life. The replies showed that 58 = 25% had had conjunctivitis, of whom 17% had been treated with antibiotics.
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A single blind study of 10 days' randomly allocated treatment with erythromycin (1000 mg/day) and roxithromycin (300 mg/day) in 14 (group A) and 13 (group B) adults, respectively, all with culture-proven chlamydial conjunctivitis was performed. For comparison, 14 days' treatment with 1 g erythromycin daily given to 35 adults (Group C) with chlamydial conjunctivitis was also evaluated. Follow-up was made approximately one month after start of therapy. Only 2 of the 37 men and 1 of the 25 women studied, all of whom had signs of conjunctivitis, had noticed concomitant symptoms of infection from the genital tract. Nasopharyngeal cultures were chlamydia-positive in 7 (50%), 7 (54%) and 20 (57%) of the patients in Group A, B and C, respectively, while for genital cultures the corresponding figures were 9 (64%), 8 (62%) and 23 (66%), respectively. The course with erythromycin in group C cured the conjunctivitis in 34 (97%) of the patients both clinically and microbiologically. Ten days' treatment with the same dose (Group A) did not eradicate chlamydiae from the eye in one, from the nasopharynx in 5 and from the genital tract in still another patient. The roxithromycin treatment (Group B) resulted in negative chlamydial cultures from the eyes in all 13 cases, while the nasopharyngeal and genital cultures were still positive in one patient each. The study showed that in spite of the eye being cured by macrolide therapy, other sites like the nasopharynx and the genital tract may still be colonized, why sampling for C. trachomatis from these sites should be made in tests for cure in chlamydial conjunctivitis cases.(ABSTRACT TRUNCATED AT 250 WORDS)
In this study, we examined the temporal antibody response by immunoblotting analysis in tears and sera of three cynomolgus monkeys (Macaca fasicularis) with primary acute Chlamydia trachomatis serovar B conjunctivitis. The objective was to identify chlamydial antigens stimulating antibody during the host responses in the course of this self-limiting infection with the rationale that they may be protective antigens. The major outer membrane protein (MOMP), lipopolysaccharide (LPS), and polypeptides of 60 and 68 kilodaltons (kDa) were the predominant antigens recognized by immunoglobulin A (IgA) in monkey tears. Tear IgA antibody specific for the MOMP was first detected 14 days postinfection, whereas tear IgA reactive with LPS or the 68- and 60-kDa polypeptides was first detectable on day 21. Tear IgA antibodies specific for each of these antigens persisted in tears through day 56, 4 weeks after both peak clinical disease and recovery of the organism from the conjunctivae. In contrast, tear IgG antibodies peaked at approximately 28 days postinfection, the time of maximal inflammatory response. The IgG response in monkey sera was similar to that observed for tear antibodies, in that the MOMP, 60-, and 68-kDa polypeptides were the primary immunogens. The exception was that IgG antibody against these antigens was detected 1 week later than that observed for tear IgA antibodies. Of three monkeys that responded with tear IgA antibody against LPS, one did not have detectable serum IgG LPS antibody. The specificity of the tear IgA antibody response of monkeys was determined by immunoblotting nine other C. trachomatis serovars in addition to the homologous B serovar. The tear IgA response to the MOMP was predominantly B complex subspecies-specific (serovars B, Ba, D, and E), whereas the response to chlamydial LPS was found to be species-specific. The significance of these observations in relation to previous vaccine studies in nonhuman primates is discussed.
Antigen-specific responses to chlamydiae have been demonstrated with lymphocytes isolated from the conjunctiva after primary ocular infection and after topical challenge of chlamydia-immune cynomolgus monkeys with noninfectious, Triton X-100-extracted antigen. Proliferative to viable elementary bodies homologous to the original infecting serovar were demonstrated. In addition, in vitro production of antichlamydial antibody by conjunctival B cells was demonstrated by enzyme-linked immunosorbent assay of culture supernatants collected after 7 to 21 days of culture. These findings demonstrate that antigen-specific lymphocytes appear in the conjunctiva as a result of ocular chlamydial infection and that a noninfectious chlamydial antigen stimulates their reappearance or expansion at the site of original infection.
Trachoma and sexually transmitted diseases caused by Chlamydia trachomatis are major health problems worldwide. Epitopes on the major outer membrane protein (MOMP) of C. trachomatis have been identified as important targets for the development of vaccines. In order to examine the immunogenicity of a recombinant vector expressing a chlamydial epitope, a poliovirus hybrid was constructed in which part of neutralization antigenic site I of poliovirus type 1 Mahoney (PV1-M) was replaced by a sequence from variable domain I of the MOMP of C. trachomatis serovar A. The chlamydial sequence included the neutralization epitope VAGLEK. This hybrid was viable, grew very well compared with PV1-M, and expressed both poliovirus and chlamydial antigenic determinants. When inoculated into rabbits, this hybrid was highly immunogenic, inducing a strong response against both PV1-M and C. trachomatis serovar A. Antichlamydia titers were 10- to 100-fold higher than the titers induced by equimolar amounts of either purified MOMP or a synthetic peptide expressing the VAGLEK epitope. Furthermore, rabbit antisera raised against this hybrid neutralized chlamydial infectivity both in vitro, for hamster kidney cells, and passively in vivo, for conjunctival epithelia of cynomolgus monkeys. Because poliovirus infection induces a strong mucosal immune response in primates and humans, these results indicate that poliovirus-chlamydia hybrids could become powerful tools for the study of mucosal immunity to chlamydial infection and for the development of recombinant chlamydial vaccines.
Intramuscular inoculation of the monkey with a massive dose of Chlamydia agent particles resulted in the production of high levels of immunoglobulin M antibodies. These antibodies were broadly specific and reacted to high titers with heterologous antigens. Challenge inoculation of the same monkeys with heterologous Chlamydia agent particles resulted in the production of increased levels of immunoglobulin G but not immunoglobulin M antibodies. Some immunological implications of these results are discussed.
Highly purified trachoma elementary bodies (T'ang strain), incubated in the presence of the four nucleoside triphosphates [Mg(2+), Mn(2+), 2-mercaptoethanol, tris(hydroxymethyl)aminomethane buffer (pH 7.5)] were found to incorporate (3)H-uridine triphosphate (UTP) into ribonucleic acid (RNA) molecules. Eighty-seven per cent of the labeled molecules were sensitive to ribonuclease treatment. In vitro RNA synthesis was almost completely inhibited by actinomycin D. Rifampin was also inhibitory, but allowed some initial RNA synthesis before complete inhibition occurred. When the reaction mixture lacked Mn(2+), trachoma elementary bodies synthesized, for a limited period, high-molecular-weight RNA species (23 to 24S, 16 to 17S, and 10 to 11S). Addition of 0.2 m NaCl to the same reaction mixture stimulated and prolonged (3)H-UTP incorporation into the same radioactive RNA species. Addition of 0.001 m Mn(2+) instead of NaCl also stimulated (3)H-UTP incorporation but prevented the synthesis of the high-molecular-weight RNA species.
An improved solid-phase enzyme immunoassay (EIA) with Chlamydia trachomatis L2 434/Bu elementary bodies was developed for the measurement of immunoglobulin M (IgM) antibody to C. trachomatis in serum. Comparison of EIA and microimmunofluorescence IgM antibody titers of 156 serum samples revealed an EIA sensitivity and specificity of 100% for infants, but reduced sensitivity (85%) and specificity (76%) for sera from adults. Sera containing IgM class rheumatoid factor produced false-positive IgM results which could easily be eliminated by pretreatment of the sera with anti-human IgG. Analysis of sera from infants with chlamydial infections revealed that 17 of 17 infants with C. trachomatis pneumonia had high IgM antibody titers (geometric mean titer, 1:64,812), whereas two infants with conjunctivitis only lacked detectable IgM antibody. EIA detected IgM antibody to several serovar groups in serum, including serovars B, BDE, FG, and J. IgM antibody to C. trachomatis in serum was detected as early as 5 days after the infection that was acquired at delivery and persisted for 3 months. The availability of an EIA possessing good sensitivity and specificity for the detection of IgM antibody to C. trachomatis may permit more laboratories to diagnose perinatal chlamydial infections.