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Query: UMLS:C0032285 (pneumonia)
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T cell-mediated immunity as measured by delayed-type hypersensitivity, and IFN-gamma production has been shown to be critical for host defense against Chlamydia trachomatis infection in both human and animal studies. Using gene-targeted B cell-deficient mice, we examined the role of B cells in protective immunity to C. trachomatis (mouse pneumonitis) (MoPn) lung infection. B cell-deficient mice were observed to have a significantly higher mortality rate and in vivo chlamydial growth than did wild-type mice following MoPn lung infection. Interestingly, B cell-deficient mice not only lacked Ab responses but also failed to mount an efficient delayed-type hypersensitivity response following chlamydial lung infection. In contrast to results obtained from MoPn-infected wild-type C57BL/6 mice, spleen cells from infected B cell-deficient mice failed to produce Th1-related (IFN-gamma) or Th2-related (IL-6 and IL-10) cytokines after Chlamydia-specific in vitro restimulation. Moreover, unlike wild-type mice, B cell-deficient mice were not immune to rechallenge infection following recovery from primary chlamydial infection. The data indicate that B cells play an important role in host defense to primary and secondary chlamydial infection and suggest that B cells are crucial for the initiation of early T cell responses to chlamydial infection. This study provides evidence for the role of B cells in the in vivo priming of T cells during infection with the intracellular bacterial pathogen, C. trachomatis.
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PMID:Gene knockout B cell-deficient mice demonstrate that B cells play an important role in the initiation of T cell responses to Chlamydia trachomatis (mouse pneumonitis) lung infection. 968 9

To characterize the role of specific lymphocyte subsets in Chlamydia trachomatis infection, we established a murine model using the mouse pneumonitis agent (MoPn) of C. trachomatis and C.B-17 scid/scid (SCID) mice which lack functional B and T cells. After intraperitoneal inoculation with the bacteria, SCID mice developed polyserositis with pleuritis, pericarditis, and perihepatitis. Within 8 weeks post infection, SCID mice succumbed to the disease, whereas immunocompetent congenic C.B-17+/+ mice resolved the infection. Adoptive transfer of immune spleen cells into MoPn-infected SCID mice resulted in a complete elimination of the agent and prevention of polyserositis as measured by quantitative chlamydial culture, direct immunofluorescence and histopathological analysis. Selective reconstitution of MoPn-infected SCID mice with immune B lymphocytes, CD4+ T cells or CD8+ T cells alone did not influence the chlamydial load in the lung and liver of infected SCID animals, resulting in a polyserositis as observed in untreated MoPn-infected SCID mice. However, co-transfer of both CD4+ T cells and CD8+ T cells led to a significant reduction of chlamydiae in quantitative organ culture coupled with unremarkable histopathology. These data confirm that T cell-mediated immune responses are essential for immune protection in chlamydial infection, although total eradication of the agent could not be achieved. Further experiments are needed to stress the importance of a concerted action of B and T lymphocytes, as indicated by the complete protective efficacy of transferred splenocytes.
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PMID:Clearance of Chlamydia trachomatis-induced polyserositis in SCID mice requires both CD4+ and CD8+ cells. 983 20

In women, Chlamydia trachomatis infection often occurs in the urethra or cervix, with up to 70% of infections associated with few or no symptoms. Inadequate treatment may lead to infection of the upper genital tract and subsequent pelvic inflammatory disease (PID) in 10 to 40% of patients. PID causes an increased relative risk of ectopic pregnancy of 2.5 to 7.9 and PID may also lead to tubal infertility in about 17% of patients. 60% of infants born of mothers with C. trachomatis infection may become infected, leading to conjunctivitis in 23% and pneumonia in 21%. All of these sequelae of C. trachomatis infection may require in- or outpatient treatment. With > 4 million infections estimated to occur each year in the US, C. trachomatis is one of the most common and costly of the sexually transmitted pathogens. Treatment options for uncomplicated C. trachomatis infections in nonpregnant women include single-dose azithromycin 1000 mg or doxycycline 100 mg twice daily for 7 days orally. In clinical trials, the bacteriological cure rate of single dose azithromycin 1000 mg (95 to 100%) was similar to that of oral doxycycline 200 mg/day for 7 days (88 to 100%) in nonpregnant women. Azithromycin was at least as well tolerated as doxycycline and was associated with mainly mild gastrointestinal adverse effects including diarrhoea, nausea and abdominal pain. Pharmacoeconomic analyses have sought to determine if the 2.7- to 12-fold higher acquisition costs of azithromycin in comparison with doxycycline are offset by its simple single-dose regimen which is likely to aid patient compliance and so optimise drug efficacy. All analyses were retrospective cost-effectiveness decision-tree models and mainly considered direct costs. All models incorporated an estimate of noncompliance with doxycycline and its influence on efficacy. For the treatment of confirmed C. trachomatis infection, azithromycin saved around $US1200 per major outcome avoided (1993 values; third-party payer perspective in the US) or US$3502 per case of PID avoided (1993 values; US healthcare system perspective) compared with doxycycline. If infection was treated empirically, azithromycin was more costly than doxycycline by $US792 (1993 values), but the result was sensitive to changes of some parameters of the model. Azithromycin was more costly than doxycycline from the perspective of a public health clinic which paid for the treatment of initial infection and acute sequelae only. Thus, pharmacoeconomic data from the US support the use of azithromycin in the treatment of nonpregnant women with confirmed C. trachomatis urogenital infections from the perspective of the healthcare system or third-party payer; however, from the perspective of a public clinic, doxycycline is the less costly option. Decreases in doxycycline compliance or azithromycin acquisition cost are factors that favour azithromycin.
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PMID:Azithromycin. A pharmacoeconomic review of its use as a single-dose regimen in the treatment of uncomplicated urogenital Chlamydia trachomatis infections in women. 1017 26

We previously reported that DNA vaccination was able to elicit cellular immune responses and partial protection against Chlamydia trachomatis infection. However, DNA immunization alone did not generate immune responses or protection as great as that induced by using live organisms. In this study, we evaluated the immunologic effects of a combinational vaccination approach using C. trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) DNA priming followed by boosting with immune-stimulating complexes (ISCOM) of MOMP protein (MOMP ISCOM) for protection of BALB/c mice against MoPn lung infection. Substantially better protection to challenge infection was observed in mice given combinational vaccination compared with mice given MOMP ISCOM immunization alone, and the protection approximated that induced by live organisms. Enhanced protection was correlated with stronger delayed-type hypersensitivity, higher levels of gamma interferon production, and increased immunoglobulin A antibody responses in lung homogenates. The results indicate that DNA priming followed by ISCOM protein boosting may be useful in designing a fully protective chlamydial vaccine.
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PMID:Priming with Chlamydia trachomatis major outer membrane protein (MOMP) DNA followed by MOMP ISCOM boosting enhances protection and is associated with increased immunoglobulin A and Th1 cellular immune responses. 1081 46

Cellular and humoral immune responses induced following murine Chlamydia trachomatis infection confer almost sterile protection against homologous reinfection. On the other hand, immunization with inactivated organism induces little protective immunity in this model system. The underlying mechanism(s) that determines such divergent outcome remains unclear, but elucidating the mechanism will probably be important for chlamydial vaccine development. One of the distinct differences between the two forms of immunization is that chlamydia replication in epithelial cells causes the secretion of a variety of proinflammatory cytokines and chemokines, such as GM-CSF, that may mobilize and mature dendritic cells and thereby enhance the induction of protective immunity. Using a murine model of C. trachomatis mouse pneumonitis lung infection and intrapulmonary adenoviral GM-CSF transfection, we demonstrate that the expression of GM-CSF in the airway compartment significantly enhanced systemic Th1 cellular and local IgA immune responses following immunization with inactivated organisms. Importantly, immunized mice had significantly reduced growth of chlamydia and exhibited less severe pulmonary inflammation following challenge infection. The site of GM-CSF transfection proved important, since mice immunized with inactivated organisms after GM-CSF gene transfer by the i.p. route exhibited little protection against pulmonary challenge, although i.p. immunization generated significant levels of systemic Th1 immune responses. The obvious difference between i.p. and intrapulmonary immunization was the absence of lung IgA responses following i.p. vaccination. In aggregate, the findings demonstrate that the local cytokine environment is critical to the induction of protective immunity following chlamydial vaccination and that GM-CSF may be a useful adjuvant for a chlamydial vaccine.
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PMID:GM-CSF transgene-based adjuvant allows the establishment of protective mucosal immunity following vaccination with inactivated Chlamydia trachomatis. 1244 39

This chapter deals with genital chlamydial infections in pregnancy and postpartum. There is increasing evidence that Chlamydia trachomatis infection may result in a number of adverse pregnancy outcomes, including early and late abortion, intrauterine infections of the fetus, stillbirth, prematurity, premature rupture of the membranes (PROM) and postpartum endometritis. Ectopic pregnancy is commonly associated with a previous tubal chlamydial infection where immunological reactions seem to play a role. C. trachomatis infection may be acquired as an intrauterine infection, as well as during transit through the birth channel, and this may result in neonatal conjunctivitis and/or pneumonia. The role of chlamydial infection in the sudden death syndrome has also been considered, but evidence so far is minimal. Neonatal chlamydial infection may cause life-long sequelae, such as obstructive lung disease. Genital chlamydial infections have been associated with problems in insemination and attempts at in vitro fertilization. The chapter also deals with screening of pregnant women for C. trachomatis and the treatment of infected mothers and their offspring.
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PMID:Influence of infection with Chlamydia trachomatis on pregnancy outcome, infant health and life-long sequelae in infected offspring. 1247 86

The Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes' summarises the current scientific position on the diagnosis and treatment of a great number of sexually transmitted diseases (STD) and neonatal herpes. Symptomatic treatment of suspected Chlamydia trachomatis infection and gonorrhoea without previous diagnosis is not recommended. Treatment can be started immediately, once samples have been taken. Risk groups eligible for screening or proactive testing on C. trachomatis infection include: partners of C. trachomatis-positive persons, visitors of STD clinics, women who will undergo an abortion, mothers of newborns with conjunctivitis or pneumonitis, young persons of Surinam or Antillean descent, young women with new relationships and individuals whose history indicates risky sexual behaviour. A period of 3 months can be adopted between a risky contact and the HIV test (this used to be 6 months), unless post-exposure prophylaxis was used. For the treatment of early syphilis no distinction is drawn between HIV-infected and non-HIV-infected persons. It is no longer recommended that women in labour with a history of genital herpes are tested for the herpes simplex virus. Virological testing of the neonate is only advised if the mother shows signs of genital herpes during delivery.
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PMID:[Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes']. 1272 32

Chlamydia trachomatis infection is the most common sexually transmitted infection. It can cause pelvic inflammatory disease and subsequently result in tubal infertility. Chlamydia trachomatis infection in pregnancy can also cause neonatal conjunctivitis and pneumonia. This descriptive study showed that Chlamydia trachomatis infection of the cervix among pregnant women, more than 37 weeks of gestation, attending the prenatal clinic at King Chulalongkorn Memorial hospital was found in 10 per cent by means of multiplex polymerase chain reaction (PCR) technique and 2 per cent by using culture method. The present study demonstrated that all the 182 newborn infants had no neonatal Chlamydia trachomatis infection by using multiplex PCR and culture method. All the babies had Apgar's score of more than 7. At 2 months follow-up, 155 infants were evaluated and had no evidence of Chlamydia trachomatis infection.
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PMID:The prevalence of Chlamydia trachomatis infection in pregnant Thai women. 1293 16

To find a new marker for sero-diagnosis of Chlamydia trachomatis infection, Western blot (WB) method was performed by using C. trachomatis infected HeLa229 cell extract (L2-ext) as antigen. Two series of sera of patients with pneumonia or cervicitis (4 sera each) were used for investigation and analysis of a band which fades earlier than others depending on weeks or antibody levels after therapeutic treatment. A 17 KDa band was found which tended to fade gradually, but did not completely disappear within the period of investigation. The band was also detected in sera of patients with cervicitis diagnosed by detection of C. trachomatis organisms (IDEIA-PCE Chlamydia (IDEIA) or Clearview test were positive at first visit to the clinic). Ten anti-C. pneumoniae antibody positive sera and five anti-Mycoplasma pneumoniae antibody positive sera were also tested as controls. The result was that a 17 KDa band was detected in 20 of 25 sera (80%) with IDEIA positive. 18 of 33 patients (54.5%) with Clearview positive-, and 12 of 16 (75%) sera with both tests positive. No band was found in the control sera. The frequency of antibody against 17 KDa antigen was almost completely identical with that obtained by microimmunofluorescence test and Peptide-Chlamydia-IgG test. These results show that a 17 KDa band may be used as a marker for detection of C. trachomatis antibody by the WB method. The antigen could be precipitated with salting out from the L2-ext with 60% saturation of ammonium sulfate of Hofmeister's method and it was digested with proteinase K. From the result of the amino acid sequence analysis, it was found that 17 KDa protein is the human nucleoside diphosphate kinase B.
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PMID:[Analysis of an antigen in Chlamydia trachomatis infected-cell extract which reacts with sera of patients with C. trachomatis infection]. 1460 16

T-helper-1-like cytokine response and cell-mediated immunity have been shown to be critical in host resistance to Chlamydia trachomatis infection. Using a murine pneumonia model, we compared the susceptibility of C3H/HeN (C3H) and C57BL/6 mice to C. trachomatis mouse pneumonitis (MoPn) infection. C3H mice exhibited significantly higher mortality, greater organism growth and much more severe pathological changes in the lung compared with C57BL/6 mice. However, the pattern of adaptive immune responses including organism-specific delayed-type hypersensitivity, antibody responses and cytokine [interferon-gamma (IFN-gamma), interleukin-12 (IL-12), IL-4, IL-10 and tumour necrosis factor alpha] production by spleen and local draining lymph node cells in these two strains of mice appeared comparable during the process of infection. Interestingly, MoPn growth in the cultured ex vivo macrophages from C3H mice was found to be significantly less inhibited by the exogenous IFN-gamma present in the culture compared to C57BL/6 mice. The lower inhibition of MoPn growth in C3H mice was associated with significantly lower nitric oxide production by the infected macrophages following IFN-gamma stimulation. The data suggest that the cellular events downstream of cytokine production in chlamydia host cells may be important in determining the different susceptibility of hosts to chlamydial infection.
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PMID:Less inhibition of interferon-gamma to organism growth in host cells may contribute to the high susceptibility of C3H mice to Chlamydia trachomatis lung infection. 1505 83


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