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Evaluation of serological tests for screening of chlamydial eye diseases.

Trachoma is recognized as one of most important origins of blindness in developing countries and inclusion conjunctivitis is associated with STD in developed countries. We evaluated the diagnostic value of serological tests for the screening of eye diseases associated with Chlamydia trachomatis infection. We determined serum IgG, IgA and IgM antibodies to C. trachomatis from 53 Japanese patients with active inflammatory trachoma (aged more than 60 years) and from 107 adult patients (aged 20 to 50 years) with acute inclusion conjunctivitis by ELISA test kit. We detected serum IgG antibodies from 22 out of 53 (42.5%) patients with trachoma and from 40 out of 107 (37.4%) patients with acute inclusion conjunctivitis. We also detected serum IgM antibodies from 7 out of 53 (13.2%) patients with trachoma and from 35 out of 107 (32.7%) patients with acute inclusion conjunctivitis. The prevalence of serum IgM antibodies to C. trachomatis in patients with acute inclusion conjunctivitis was significantly higher than that in patients with active trachoma (p < 0.05). Serological tests are also thought to be useful for screening of chlamydial eye diseases.

Adult↗

Chlamydiae as pathogens--an overview of diagnostic techniques, clinical features, and therapy of human infections.

Chlamydiae are Gram-negative bacteria with obligate intracellular reproduction and disability to synthesize high-energy compounds such as ATP. Their cycle of development is unique among the prokaryotes: the host cells, mainly epithelial cells, are infected by so-called elementary bodies (EB) which undergo reorganization to form metabolically active reticulate bodies (RB). These RB multiply by binary fission, and after transition into infectious EB they are released within 48-72 hours. Chlamydiae cause prolonged subclinical infections of the conjunctiva, lung, cervix, and urethra. Complications in newborns are inclusion conjunctivitis, nasopharyngitis and pneumonia; in females, salpingitis, infertility, and perihepatitis; in male patients, epididymitis and prostatitis; and in both sexes, Chlamydiae-induced arthritis. Identification of the pathogenic agent confirms clinical diagnosis; tissue culture identification remains the diagnostic method of choice. Therapeutical drugs are tetracycline, erythromycin, josamycin, and in certain cases quinolone derivatives.

Animals↗

Is trachoma an ocular component of a more generalised chlamydial infection?

In industrialised countries, inclusion conjunctivitis of the newborn is now known to be just one manifestation of a more generalised infection with Chlamydia trachomatis. Pneumonia and enteric infection can develop in perinatally infected infants. It is possible that trachoma in developing countries may reflect extraocular infection that may contribute to the high frequency of pneumonia and diarrhoea in infants in these countries. If true, this would explain the short-term effects of topical treatment, since children could reinfect their eyes by autoinoculation from other sites. Thus systemic treatment with macrolides would result in benefits beyond the temporary suppression of eye disease.

Administration, Oral↗

[Chlamydial disease of the eye: a report on 27 cases. Clinical picture, differential diagnosis, treatment (author's transl)].

During the past five years a presumptive diagnosis of ocular chlamydial disease has been made in 90 patients consulting the outpatient department of Freiburg University Eye Clinic. The diagnosis was confirmed by different methods (giemsa stains, chlamydia cultures and serology, electron microscopy and histology) in 27 cases. The clinical spectrum included inclusion blennorrhea in newborns as well as inclusion conjunctivitis, TRIC keratoconjunctivitis and sporadic trachoma in adults. Presumably the incidence of the disease is much higher than indicated by our figures. We suspect a very high number of undiagnosed cases. These patients usually do not receive proper therapy (tetracyclin or erythromycin for at least three weeks) and their disease may run a protracted course with the risk of permanent eye damage.

Adolescent↗

Respiratory-tract colonization and a distinctive pneumonia syndrome in infants infected with Chlamydia trachomatis.

To learn if Chlamydia trachomatis causes in young infants a distinctive penumonia characterized by chronic, afebrile course, diffuse lung involvement and elevated serum immunoglobulins G and M, 47 black infants four to 24 weeks of age were examined for nasopharyngeal shedding of C. trachomatis and serum immunofluorescent antibody to lymphogranuloma venereum Type I. Nasopharyngeal C. trachomatis was found in 18 of 20 with the pneumonia syndrome, two of 15 with various other illnesses and 10 of 12 with inclusion conjunctivitis but without lower respiratory illness. Chlamydial antibody titers of infants with the pneumonia syndrome were significantly elevated (geometric mean-1, pneumonia vs. conjunctivitis = 24,833 vs. 1024 P less than 0.001). No other commonly recognized respiratory pathogens were consistently associated with the pneumonia syndrome. We believe these findings demonstrate an association between the distinctive pneumonia syndrome and C. trachomatis. This, in turn, is a particular facet of a more general event consisting of frequent colonization of the respiratory tract by C. trachomatis in natally acquired infection.

Antibodies, Bacterial↗

Role of Chlamydia trachomatis in perinatal infection.

The transmission of Chlamydia trachomatis from the infected cervix of a mother to the eye of an infant, with resultant inclusion conjunctivitis, was documented in humans and in primates 75 years ago by cytologic methods. With modern microbiologic methodology it is possible to quantitate this transmission. It is now known that 2%-24% (usually 7%-12%) of cervices are infected before delivery and that 18%-50% (usually 20%-25%) of infants born to culture-positive mothers develop conjunctivitis. In addition, nasopharyngeal infection occurs in 15%-20% of infants, and 3%-18% develop pneumonia due to C. trachomatis. Bronchiolitis and otitis media are less common infections. The consequence of rectal and vaginal colonization remains unknown, as does the significance of the increase in antibody titers against C. trachomatis throughout early childhood. Early studies suggesting that C. trachomatis was a prominent cause of postpartum endometritis and a cause of premature delivery have not been confirmed in larger prospective studies when mycoplasma species were simultaneously studied. A subset of mothers with active infection, as evidenced by IgM antibody against C. trachomatis, may have earlier delivery, but it is clear that evaluation of the contribution of C. trachomatis to maternal and fetal risk will require larger studies with evaluation of possible concurrent mycoplasmal infection.

Chlamydia Infections↗

Serology of Chlamydia trachomatis in infants.

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.

Antibodies, Viral↗

Superoxide dismutase activity in polymorphonuclear leukocytes and alveolar macrophages of protein malnourished rats and guinea pigs.

Chronic protein insufficiency in utero was achieved by feeding to rat dams an 8% protein diet beginning before breeding and continuing until weaning. Thereafter, the in utero malnourished pups were fed the 8% protein diet. Superoxide dismutase (SOD), an enzyme which protects against superoxide radical, was quantitated in pellet and supernatant of polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM). The AM of rats malnourished in utero contained 1.7 times as much protein and 3 times as much total SOD activity as the AM of control rats. In PMN of these rats, the amount of protein and SOD activity was the same. Significantly larger number of Streptococcus mutans were located from the dental plaque of the in utero malnourished rats. AM isolated from female guinea pigs fed a 9% protein diet from weaning at 11 days of age contained 1.5 times as much protein and twice as much SOD activity as AM from normal guinea pigs. However their PMN contained smaller amounts of total protein and SOD activity. The malnourished guinea pigs had a mammary gland infection and a prolonged conjunctival infection following inoculation with Guinea Pig Inclusion Conjunctivitis indicating that these animals were more susceptible to these infections. The increase in total SOD activity and in the total amount of protein in AM suggests that chronic protein insufficiency leads to susceptibility to infection and to macrophage activation but has no similar effects on PMN.

Animals↗

Inapparent chlamydial infection in the urogenital tract of guinea-pigs.

Microbiologically inapparent urogenital infection appeared to be induced in male guinea-pigs inoculated intra-urethrally with low doses of the guinea-pig inclusion conjunctivitis strain (GP-IC) of Chlamydia psittaci. This state was indicated by the ability of inoculated animals to donate eye infection to normal animals caged with them. Donors failed to develop overt urogenital infection throughout the period of transmission judged by both absence of infected cells in urethral scrapings and failure to isolate GP-IC in cell culture; however, inoculation of donors with 5-iododeoxyuridine led to transient appearance of infectivity in scrapings. In distinction from overtly infected animals, donors failed to develop serum antibody and remained susceptible to urethral challenge with larger doses of GP-IC. Animals that had recovered from overt urethral infection were resistant to challenge and appeared unable to transmit eye infection.

Animals↗

A 28 kDa major immunogen of Chlamydia psittaci shares identity with Mip proteins of Legionella spp. and Chlamydia trachomatis-cloning and characterization of the C. psittaci mip-like gene.

Chlamydia psittaci strain guinea-pig inclusion conjunctivitis (GPIC) produces a self-limiting ocular infection of guinea-pigs, and this condition is a representative animal model of ocular chlamydial disease. Convalescent guinea-pigs, which are resistant to reinfection, produce antibodies to several elementary-body proteins, including an uncharacterized antigen of 28 kDa. Convalescent guinea-pig sera were used to identify, from a lambda expression library, two overlapping GPIC genomic clones that produced the 28 kDa antigenic protein. Nucleotide sequence analysis revealed that the gene coding for the 28 kDa protein was similar to the mip (macrophage infectivity potentiator) genes from Legionella pneumophila and Chlamydia trachomatis. The GPIC gene and its product were accordingly designated mip and Mip, respectively. Analysis of the regions flanking mip identified three tightly linked open reading frames coding for predicted products with sequence similarity to asparagine tRNA ligase (AspS), rRNA methylase (SpoU), and thioredoxin (TrxA). The arrangement of these genes in GPIC was aspS-mip-spoU-trxA. Sequence analysis of PCR products produced using genomic DNA from an ovine abortion strain of C. psittaci and from C. trachomatis strain LGV-434 demonstrated that the arrangement of mip, spoU and trxA is common among these chlamydiae.

Amino Acid Sequence↗

Specific effect of estradiol on the genital mucosal antibody response in chlamydial ocular and genital infections.

Estradiol treatment of female guinea pigs was found to alter the course of genital, but not ocular, infection with the chlamydial agent of guinea pig inclusion conjunctivitis. Immunoglobulin G (IgG) and IgA responses in genital secretions of genitally infected animals were delayed by estradiol treatment, but neither response in the eye resulting from either ocular or genital infection was affected. However, the appearance of IgG in the genital tract after ocular infection was markedly inhibited in estradiol-treated guinea pigs.

Animals↗

Role of Bcl-2 family members in caspase-independent apoptosis during Chlamydia infection.

Infection with an obligate intracellular bacterium, the Chlamydia trachomatis lymphogranuloma venereum (LGV/L2) strain or the guinea pig inclusion conjunctivitis serovar of Chlamydia psittaci, leads to apoptosis of host cells. The apoptosis is not affected by a broad-spectrum caspase inhibitor, and caspase-3 is not activated in infected cells, suggesting that apoptosis mediated by these two strains of Chlamydia is independent of known caspases. Overexpression of the proapoptotic Bcl-2 family member, Bax, was previously shown to induce caspase-independent apoptosis, and we find that Bax is activated and translocates from the cytosol to the mitochondria in C. psittaci-infected cells. C. psittaci-induced apoptosis is inhibited in host cells overexpressing Bax inhibitor-1 and is inhibited through overexpression of Bcl-2, which blocks both caspase-dependent and -independent apoptosis. As Bax and mitochondria are ideally located to sense stress-related metabolic changes emanating from the interior of an infected cell, it is likely that Bax-dependent apoptosis may also be observed in cells infected with other intracellular pathogens.

Amino Acid Chloromethyl Ketones↗

Rapid serological test for diagnosis of chlamydial ocular infections.

A rapid serodiagnostic test for the diagnosis of paratrachoma (TRIC ophthalmia neonatorum, inclusion conjunctivitis, TRIC punctate keratoconjunctivitis, and trachoma of sexually transmitted origin) has been developed. The technique is based on using a modified micro-immunofluorescence test for detecting antichlamydial IgG and IgM in the blood and IgG and IgA in tears. The blood samples are collected on cellulose sponges after a finger prick, and tears are collected by introducing small sponges into the lower conjunctival fornix of the eye. The blood and tear samples collected in this way could be sent to the diagnostic laboratory by post without special arrangements for cold storage. In general the presence of antichlamydial IgG at a level of greater than or equal to 1/32 or IgM at a level of greater than or equal to 1/8 in blood and antichlamydial IgG or IgA at a level of greater than or equal to 1/8 in tears was closely associated with ocular paratrachoma. The combined results of the micro-IF test of blood and tears has yielded the highest rate of positivity (90%). In patients with acute untreated paratrachoma the sensitivity of this test was similar to that of irradiated McCoy cells. In patients with a milder infection receiving antibiotics the sensitivity of the serodiagnostic test was superior to that of the cultural test. The high sensitivity and specificity of this rapid, simple and inexpensive serodiagnostic test for the diagnosis of chlamydial ocular infections, coupled with simple and practical methods of collection and transport of blood and tear specimens, offer advantages over cultural tests for routine diagnosis and study of chlamydial ocular infections.

Antibodies, Bacterial↗

Transmission of chlamydiae by the housefly.

The ability of the housefly to carry viable Chlamydia trachomatis and to transmit a chlamydial ocular infection was studied under laboratory conditions. After feeding flies (Musca domestica) on suspensions of egg yolk sac infected with C. trachomatis serotypes A or B (responsible for hyperendemic trachoma) the agents were reisolated from flies' intestines for up to 6 hours and from their legs and/or proboscises for up to 2 hours. It was found that the viability of chlamydiae is dependent on the protective effect of yolk concentration in the original inoculum. Results of experiments with guinea-pig inclusion conjunctivitis as an animal model show that under laboratory conditions flies can readily transmit this chlamydial ocular infection from one animal to another. These results suggest that under field conditions flies can play an important role in the transmission of trachoma, particularly in areas with favourable conditions such as a large reservoir of infection among children with severe trachoma, copious eye discharge caused by trachoma and associated bacterial infections, a large fly population, and close proximity of children in large family groups.

Animals↗

[Chlamydia and Mycoplasma infections of newborns].

Chlamydia trachomatis and the urogenital mycoplasmas are sexually transmitted microorganisms mutually infecting the sexual partners. Transmission from mother to child occurs in utero or, in particular, perinatally when the delivered child passes through the infected cervix. Diseases of newborns infected by Chlamydia trachomatis are inclusion conjunctivitis or infant chlamydial pneumonia. In very-low-birth-weight infants perinatal infections by urogenital mycoplasmas induce pneumonia, septicemia, and chronic lung disease.

Chlamydia Infections↗

Chlamydia trachomatis infections in infants.

In recent years considerable progress has been made in understanding chlamydial infections. The spectrum of pediatric Chlamydia trachomatis infection includes neonatal inclusion conjunctivitis, infantile pneumonia, occasional respiratory or genital tract infections in older children and sexually transmitted diseases in adolescents. The role of maternal chlamydial infection in prematurity and in perinatal death is currently an area of active study. We outline the current knowledge of the biologic characteristics of C. trachomatis, the epidemiologic features of chlamydial infection, and the clinical aspects, diagnosis and treatment of neonatal chlamydial infections.

Chlamydia Infections↗

Rapid, inexpensive confirmation of chlamydial infection.

This article will hopefully make all optometrists aware of a rapid, direct method for confirming a diagnosis of chlamydial (inclusion) conjunctivitis. The Micro-Trak test from Syva is inexpensive, highly specific, and very sensitive for all human serovars of Chlamydia trachomatis. The current regimens for chlamydial conjunctivitis are also described.

Conjunctivitis, Inclusion↗

Prospective study of perinatal transmission of Chlamydia trachomatis.

During a five-year period, 262 (4.7%) of 5,531 pregnant women had positive cervical cultures for Chlamydia trachomatis, and 131 of their infants were followed up prospectively to ascertain the outcome of chlamydial exposure during the birth process. Culture-confirmed inclusion conjunctivitis of the newborn was seen in 23 (18%) of the infants. Chlamydial pneumonia was diagnosed in 21 (16%) of the infants at risk. Chlamydia trachomatis was recovered from 47 of the infants (36%), while 79 (60%) showed serologic evidence of infection. Subclinical rectal and vaginal infections were detected in 14% of infants at risk. In our population, 2.8% of newborn infants show serologic evidence of perinatal chlamydial infection and 1.4% develop either chlamydial pneumonia or conjunctivitis. Incidence rates of this magnitude indicate the need for programs aimed at preventing perinatal transmission of C trachomatis.

Antibodies, Bacterial↗