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PubMed1994

Mice immunized with a chlamydial extract have no increase in early protective immunity despite increased inflammation following genital infection by the mouse pneumonitis agent of Chlamydia trachomatis.

We have determined that immunization with a detergent extract of the mouse pneumonitis agent of Chlamydia trachomatis fails to induce a protective inflammatory immune response following genital infection by C. trachomatis. We demonstrated that mice immunized with the detergent extract have increased cutaneous delayed-type hypersensitivity and increased splenic T-cell proliferation in response to the chlamydial extract. After genital infection by C. trachomatis, extract-sensitized mice had significantly increased genital inflammation (P = 0.044) compared with controls. The inflammation was characterized by significantly increased eosinophils in the genitalia (P < 0.0005) and increased genital edema (P < 0.0005). However, the increased genital inflammation of extract-sensitized mice provided no increase in protection against infection (P = 0.92).

Animals↗
PubMed1995

Tumor necrosis factor alpha activity in genital tract secretions of guinea pigs infected with chlamydiae.

Previous studies using the guinea pig model of chlamydial genital infection demonstrated that primary infection is associated with a marked acute inflammatory response early on, while chronic inflammation appears later, at a time when the level of infection is reduced. Challenge infections result primarily in a chronic inflammatory response. The stimuli that initiate inflammation and lead to tissue damage have not been defined. We investigated the possibility that tumor necrosis factors (TNFs) play a role in the inflammatory response to chlamydial genital tract infection. Cytotoxicity assays for TNF were performed on genital tract secretions collected from female guinea pigs during infection with the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis. During the early days of primary infection, high levels of TNF-alpha were detected in genital tract secretions from inbred S2 strain and outbred Hartley strain guinea pigs. Significantly lower levels of TNF-alpha were detected in secretions from both strains during challenge infection. In general, the intensity of the TNF-alpha response was proportional to the intensity of infection. High TNF-alpha levels were present during primary infection at a time of marked neutrophil influx. Thus, TNF-alpha may play an important role in the response to primary chlamydial genital tract infection.

Animals↗
PubMed1995

Protective efficacy of major outer membrane protein-specific immunoglobulin A (IgA) and IgG monoclonal antibodies in a murine model of Chlamydia trachomatis genital tract infection.

The protective efficacy of immunoglobulin A (IgA) and IgG monoclonal antibodies (MAbs) specific for the major outer membrane protein of Chlamydia trachomatis MoPn was evaluated in a murine genital tract infection model. MAbs were delivered into serum and vaginal secretions of naive mice by using the backpack hybridoma tumor system, and protective efficacy was assessed over the first 8 days following challenge by quantitative determination of chlamydial recovery from cervicovaginal swabs, histopathological evaluation of genital tract tissue, and immunohistochemical detection of chlamydial inclusions. IgA and IgG significantly reduced the incidence of infection following vaginal challenge with 5 50% infectious doses, but such protection was overwhelmed by 10- and 100-fold higher challenge doses. Both MAbs also consistently reduced vaginal shedding from infected animals with all three challenge doses compared with the negative control MAb, although the magnitude of this effect was marginal. Blinded pathological evaluation of genital tract tissues at 8 days postinfection showed a significant reduction in the severity of the inflammatory infiltrate in oviduct tissue of infected IgA- and IgG-treated animals. Immunohistochemical detection of chlamydial inclusions revealed a marked reduction in the chlamydial burden of the oviduct epithelium; this finding is consistent with the reduced pathological changes observed in this tissue. These studies indicate that the presence of IgA or IgG MAbs specific to major outer membrane proteins has a marginal effect in preventing chlamydial colonization and shedding from the genital tract but has a more pronounced effect on ascending chlamydial infection and accompanying upper genital tract pathology.

Animals↗
PubMed2000

Subclinical chlamydial infection of the female mouse genital tract generates a potent protective immune response: implications for development of live attenuated chlamydial vaccine strains.

Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4(+) T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection. Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log(10)) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs.

Animals↗
PubMed2000

Induction of protective immunity against Chlamydia trachomatis genital infection by a vaccine based on major outer membrane protein-lipophilic immune response-stimulating complexes.

The significance of delivery systems in modern vaccine design strategies is underscored by the fact that a promising vaccine formulation may fail in vivo due to an inappropriate delivery method. We evaluated the immunogenicity and efficacy of a candidate vaccine comprising the major outer membrane protein (MOMP) of Chlamydia trachomatis delivered with the lipophilic immune response-stimulating complexes (ISCOMs) as a vehicle with adjuvant properties, in a murine model of chlamydial genital infection. Immunocompetent BALB/c mice were immunized intranasally (IN) or intramuscularly (IM) with MOMP, MOMP-ISCOMs, and live or heat-inactivated C. trachomatis serovar D. The level of local genital mucosal Th1 response was measured by assaying for antigen-specific Th1 cell induction and recruitment into the genital mucosa at different times after immunization. Immunization with MOMP-ISCOMs by the IM route induced the greatest and fastest local genital mucosal Th1 response, first detectable 2 weeks after exposure. Among the other routes and regimens tested, only IN immunization with MOMP-ISCOMs induced detectable and statistically significant levels of local genital mucosal Th1 response during the 8-week test period (P < 0.001). In addition, when T cells from immunized mice were adoptively transferred into syngeneic naive animals and challenged intravaginally with Chlamydia, recipients of IM immunization of MOMP-ISCOMs cleared their infection within 1 week and were resistant to reinfection. Animals that received IN immunization of MOMP-ISCOMs were partially protected, shedding fewer chlamydiae than did control mice. Altogether, the results suggested that IM delivery of MOMP-ISCOMs may be a suitable vaccine regimen potentially capable of inducing protective mucosal immunity against C. trachomatis infection.

Adjuvants, Immunologic↗
PubMed2002

Chemokine and chemokine receptor dynamics during genital chlamydial infection.

Current design strategies for vaccines against certain microbial pathogens, including Chlamydia trachomatis, require the induction and targeting of specific immune effectors to the local sites of infection known as the mucosal effector sites. Chemokines and their receptors are important mediators of leukocyte trafficking and of the controlled recruitment of specific leukocyte clonotypes during host defense against infections and during inflammation. We analyzed the dynamics of chemokine and chemokine receptor expression in genital mucosae during genital chlamydial infection in a murine model to determine how these molecular entities influence the development of immunity and the clearance of infection. A time course study revealed an increase of up to threefold in the levels of expression of RANTES, monocyte chemotactic protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1alpha (MIP-1alpha), and intercellular adhesion molecule type 1 (ICAM-1) after genital infection with the C. trachomatis agent of mouse pneumonitis. Peak levels of expression of RANTES, MCP-1, and MIP-1alpha occurred by day 7 after primary infection, while those of IP-10 and ICAM-1 peaked by day 21. Expression levels of these molecules decreased by day 42 after primary infection, by which time all animals had resolved the infection, suggesting an infection-driven regulation of expression. A rapid upregulation of expression of these molecules was observed after secondary infection. The presence of cells bearing the chemokine receptors CCR5 and CXCR3, known to be preferentially expressed on Th1 and dendritic cells, was also synchronous with the kinetics of immune induction in the genital tract and clearance of infection. Results demonstrated that genital chlamydial infection is associated with a significant induction of chemokines and chemokine receptors that are involved in the recruitment of Th1 cells into the site of infection. Future studies will focus on how selective modulation of chemokines and their receptors can be used to optimize long-term immunity against CHLAMYDIA:

Animals↗
PubMed2003

Detection of infectious human immunodeficiency virus type 1 in female genital secretions by a short-term culture method.

Infectious human immunodeficiency virus type 1 (HIV-1) is difficult to detect in female genital secretions by standard virus culture techniques. To improve detection of cell-free HIV-1 in female genital secretions, we adapted a short-term assay that uses the multinuclear-activation galactosidase indicator (MAGI) assay. When vaginal lavages from HIV-1-infected women were tested with the adapted MAGI assay, 25 (64%) of 39 lavages with detectable, cell-free HIV-1 RNA were shown to have infectious virus. No infectious virus was found in 10 vaginal lavages from HIV-1-infected women with undetectable vaginal viral loads. Significantly (P < 0.01) more lavages from HIV-1-infected women tested positive for infectious virus by the MAGI assay than by standard peripheral blood mononuclear cell (PBMC) coculture, which detected infectious virus in only 6 (17%) of 35 vaginal lavages. Lavages with viral loads of >10,000 copies per lavage yielded significantly (P < 0.01) more positive cultures than those with <10,000 copies by using the MAGI assay. Detection of infectious HIV-1 in vaginal lavages was not associated with the presence of genital tract infections or CD4(+)-T-cell counts. However, although the results were not significant (P = 0.08), the MAGI assay detected infectious virus from more vaginal lavages at a vaginal pH of >/=4.5 than at a pH of <4.5. These results indicate that the MAGI assay is more sensitive than PBMC culture methods for detecting infectious virus in female genital secretions. Accurate measurements of infectious virus in genital secretions will improve studies that evaluate sexual transmission of HIV-1.

Adolescent↗
PubMed1991

Genital ulcer disease in women in Durban, South Africa.

OBJECTIVE: To study the microbial aetiology of genital ulcer disease (GUD) in women. DESIGN: Microbial and clinical assessment of genital ulcers in women. SETTING: City Health sexually transmitted diseases clinic, King Edward VIII Hospital, Durban, South Africa. PARTICIPANTS: 100 Zulu women with genital ulceration who had not received antibiotics in the previous two weeks. RESULTS: Syphilis was diagnosed in 40%, genital herpes in 18%, donovanosis (granuloma inguinale) in 16%, chancroid in 14%, lymphogranuloma venereum in 7% and scabies in 2%. No recognised cause was detected in 18%. Secondary syphilis was diagnosed in 21%, primary syphilis in 16% and mixed primary and secondary syphilis in 3%. Multiple infections were detected in 13 women, of whom 12 had syphilis. Bleeding was observed from the ulcers of 59 during swab collection. Three women had HIV-1 antibodies. Neisseria gonorrhoeae was isolated from the ulcers and endocervix of two women and from the endocervix alone in nine. Generalised scabies was diagnosed in 14. CONCLUSIONS: All the major causes of GUD are prevalent in Zulu women in Durban: secondary syphilis was the commonest diagnosis. Donovanosis, which often presents late with large ulcers, and genital herpes are now significant problems. Mixed infections with coexisting syphilis are common. All women in this population with GUD should be treated for syphilis and receive oral antibiotics effective for chancroid and donovanosis.

Adolescent↗
PubMed1991

Genital ulcer disease in men in Durban, South Africa.

OBJECTIVE: To study the microbial aetiology of genital ulcer disease (GUD) in men. DESIGN: Microbiological and clinical assessment of genital ulcers in men. SETTING: City Health sexually transmitted diseases clinic, King Edward VIII Hospital, Durban, South Africa. PARTICIPANTS: 100 Zulu men with genital ulcers who had not received antibiotics in the previous four weeks. RESULTS: Syphilis was diagnosed in 42%, chancroid in 22%, donovanosis (granuloma inguinale) in 11%, genital herpes in 10% and lymphogranuloma venereum (LGV) in 6%. No pathogens were identified in 24%. Mixed infections were detected in 14 men, in whom 13 had syphilis. Five men had HIV-1 antibodies. Neisseria gonorrhoeae was isolated from the ulcers and urethra in seven men and from the urethra alone in five. Scabies was diagnosed clinically in eight. CONCLUSIONS: All the major causes of GUD are prevalent in Zulu men in Durban. Primary syphilis was the commonest and was invariably present in mixed infections. Donovanosis was under-reported and was associated with a long delay before presentation. In this population, genital ulcers other than superficial lesions should be treated with anti-syphilitic therapy and oral antibiotics effective against chancroid and donovanosis.

Adolescent↗
PubMed1995

Should screening of genital infections be part of antenatal care in areas of high HIV prevalence? A prospective cohort study from Kigali, Rwanda, 1992-1993. The Pregnancy and HIV (EGE) Group.

OBJECTIVE: To study the prevalence and incidence of genital infections and their association with HIV-1 infection among pregnant women in Kigali, Rwanda. SUBJECTS AND METHODS: HIV+ and HIV- pregnant women were followed prospectively during the last three months of pregnancy. At enrolment, syphilis test (RPR) on blood sample, Chlamydiae trachomatis ELISA test on cervical smear, laboratory gonococcal culture, trichomonas and candida direct examination, CD4 lymphocyte count were performed. At each monthly follow-up clinic visit until delivery, genital infections were screened in the presence of clinical signs and symptoms. RESULTS: The HIV seroprevalence rate was 34.4% (N = 1233), 384 HIV+ women and 381 HIV- women of same parity and age were enrolled. Prevalence of genital infections at enrolment was generally higher in HIV+ women than in HIV- women: syphilis, 6.3% versus 3.7% (p = 0.13); Neisseria gonorrhoea, 7.0% versus 2.4% (p = 0.005); Trichomonas vaginalis, 20.2% versus 10.9% (p = 0.0007); Chlamydia trachomatis, 3.4% versus 5.5% (p = 0.21); Candida vaginalis, 22.3% versus 20.1% (p = 0.49). Until delivery, the relative risk of acquiring genital infections was also higher in HIV+ women than in HIV- women: 1.0 for syphilis (95% CI: 0.5-2.2), 3.7 for Neisseria gonorrhoea (1.0-13.3), 2.6 for Trichomonas vaginalis (1.5-4.6) and 1.6 for Candida vaginalis (1.1-2.4). CONCLUSION: In the context of high HIV-1 seroprevalence among pregnant women, prenatal care should include at least once screening for genital infections by clinical examination with speculum and a syphilis testing in Africa.

Adolescent↗
PubMed2005

Association between the intact foreskin and inferior standards of male genital hygiene behaviour: a cross-sectional study.

This study was undertaken to determine whether non-circumcised men have inferior standards of genital hygiene behaviour, as measured by reported washing of the whole penis, compared with circumcised men. Male attenders at a sexually transmitted infections (STI) clinic at Ealing Hospital, London had routine STI tests and examinations performed and were asked about the frequency and thoroughness of genital washing. One hundred and fifty non-circumcised and 75 circumcised men were enrolled. Not always washing the whole penis, including retracting the foreskin in non-circumcised men every time they washed (defined as inferior genital hygiene behaviour) was more common in non-circumcised (26%) than circumcised men (4%) (crude odds ratio = 8.43, 95% confidence interval: 2.51-28.3, P<0.001) and those with balanitis (42% and 5%, P=0.036). Circumcised men were more likely than non-circumcised men to wash the genital area more than once a day (37% and 19%, P=0.011). Studies investigating the relationship between male circumcision status and other outcomes, for example HIV infection, should include assessment of genital hygiene.

Adolescent↗
PubMed2005

A predominant role for antibody in acquired immunity to chlamydial genital tract reinfection.

Acquired immunity to murine Chlamydia trachomatis genital tract reinfection has long been assumed to be solely dependent on cell-mediated immunity. However, in this study, we identify a previously unrecognized protective role for Ab. Immunity develops in Ab-deficient mice following the resolution of primary chlamydial genital infection. Subsequent depletion of CD4+ T cells, but not CD8+ T cells, in those immune Ab-deficient mice before secondary infectious challenge, resulted in an infection that did not resolve. Passive immunization with immune (convalescent) serum conferred a marked level of protective immunity to reinfection, which was characterized by a striking decrease in bacterial shedding, from >100,000 inclusion forming units to fewer than 10 inclusion forming units, and a shortened duration of infection. Furthermore, mAbs to the chlamydial major outer membrane protein and LPS conferred significant levels of immunity to reinfection and reduced chlamydial shedding by >100-fold. Anti-heat shock protein 60 mAb had no protective effect. In contrast to the marked protective efficacy of immune serum on reinfection, the course of primary infection was essentially unaltered by the passive transfer of immune serum. Our results convincingly demonstrate that Abs contribute importantly to immunity to chlamydial genital tract reinfection, and that Ab-mediated protection is highly dependent on CD4+ T cell-mediated adaptive changes that occur in the local genital tract tissues during primary infection. These results impact our understanding of immunity to chlamydial genital infection and may provide important insight into vaccine development.

Animals↗
PubMed2004

Identification of human papilloma viruses in male dysplastic genital lesions.

The association of Human Papillomaviruses (HPV) DNA with female genital lesions has been widely documented whereas little has been reported about male genital pathologies. The aim of this work was to investigate the presence of HPV DNA and the genotype involved in male dysplastic genital lesions. All samples were analysed by polymerase chain reaction (PCR) to amplify HPV E1 and L1 genes. The PCR products were subjected to restriction fragment length polymorphism (RFLP) to determine the HPV genotype. We analysed 209 male genital biopsies from different lesions: mostly from acuminate condylomata and from Buschke-Lowenstein tumours, Bowen papulosis, leukoplakia of the glans, scrotal lymphangioma, penile horn and penile/perianal verrucous carcinoma. Our results revealed the constant presence of viral DNA in genital condylomata, mainly associated with low risk HPV; the presence of the same genotypes was also detected in some of the examined rare pathologies.

Adult↗
PubMed2004

[Genital infections in girls with type 1 diabetes].

The aim of the study was to investigate the relation between genital infections (frequency, etiology, clinical presentation) among girls with type 1 diabetes and some factors as age of the girls, duration and metabolic control of diabetes. Forty-three girls with type 1 diabetes and twelve healthy girls for controls were involved in the study. Methods used are: genital tract inspection, direct microscopy and cultures from genital discharge and urine. Glycaemic control in the diabetic girls was assessed by measuring total glycosylated haemoglobin. The results show vulvovaginal candidiasis in 27 (62.8%) in diabetic girls versus 2 (16.6%) in controls (p < 0.01). There was clear prevalence of non-albicans Candida species. Concomitant infection with bacterial pathogens were proved in only 6 (13.9%) of diabetic girls and 1 (8.5%) of the controls. The clinical presentation of genital candidiasis was vulvovaginitis and most of the affected diabetic girls (88.9%) were in puberty period. There was no relation between duration and metabolic control of diabetes and genital infections.

Adolescent↗
PubMedDate not supplied

[Association between genital mycoplasmas and risk of preterm delivery].

The main aim of this study was to determine the prevalence of maternal colonisation by genital mycoplasmas during pregnancy and to assess its association with preterm delivery. The cervical swabs of 179 pregnant women between 8 and 16 week of gestation were cultured for Mycoplasma hominis and Ureaplasma urealyticum. Clinical details and perinatal outcomes were documented. Of a total of 179 women enrolled, 68 (38.0%) had positive cervical culture for genital mycoplasmas; 30 (16.7%) for M. hominis and 38 (21.3%) for U. urealyticum. Preterm delivery occurred in 21 (11.7%) women. Genital mycoplasmas were found more frequently in group with preterm delivery as compare to women who delivered at term (p = 0.05) and its presence at lower genital tract at early pregnancy was a risk factor of preterm delivery. Early pregnancy screening for genital mycoplasmas and following treatment may reduce the rate of preterm deliveries.

Female↗
PubMed2005

Simple clinical manifestations of genital Schistosoma haematobium infection in rural Zimbabwean women.

Up to 75% of women with urinary schistosomiasis have Schistosoma haematobium ova in the genitals. This study aimed to describe the prevalence of gynecologic S. haematobium infection and to differentiate the disease from sexually transmitted infections (STIs). Gynecologic and laboratory investigations for S. haematobium and STIs were performed in 527 women between the ages of 20 and 49 in rural Zimbabwe. Genital homogenous yellow and/or grainy sandy patches, the commonest type of genital pathology, were identified in 243 (46%) women. Grainy sandy patches were significantly associated with S. haematobium ova only. Genital S. haematobium ova was also significantly associated with homogenous yellow sandy patches, mucosal bleeding, and abnormal blood vessels. The presence of ova was not a predictor for ulcers, papillomata, leukoplakia, polyps, or cell atypia. Mucosal sandy patches seem to be pathognomonic for S. haematobium infection in the female genitals. Coexistence of ova and other lesions may not be causal.

Adult↗
PubMed1991

Genital human papillomavirus infection in men. Diagnosis and treatment with a laser and 5-fluorouracil.

One hundred twenty-eight consecutive men, sexual partners (for more than six months) of women treated for genital condylomata acuminata, were evaluated with colposcopy to assess the percentage of infected men among the couples. Ninety-three (73%) of the men were found to have a genital human papillomavirus infection on colposcopically directed biopsies. All but one patient were treated with outpatient colposcopically guided laser vaporization under local anesthesia (one patient with extensive condylomata required general anesthesia). Two weeks after laser surgery, 5% 5-fluorouracil cream, used in the genital area, was initiated on a weekly basis for two months and every other week for two more months. Patients were followed in the clinic with colposcopy performed every eight weeks for six months to evaluate the regimen's results. Thirty-seven (40%) of the 93 men had "clinically" apparent genital HPV infection, and 56 (60%) of the 93 had "subclinical" disease (as determined with colposcopy). The majority of the patients (87 of 93, or 94%) responded to one laser treatment followed by 5-fluorouracil cream and had no visible lesions at six months. Colposcopic evaluation of the male partners of infected women and laser surgery followed by topical 5-fluorouracil therapy appear to be safe and effective in controlling genital HPV infection.

Acetates↗
PubMed1989

Is genital colonization with Mycoplasma hominis or Ureaplasma urealyticum associated with prematurity/low birth weight?

Mycoplasma species have been implicated in the pathogenesis of prematurity, intrauterine growth retardation, low birth weight (LBW), and preterm premature rupture of membranes. The purpose of this study was to review the available literature to determine whether there is an association between genital colonization with Mycoplasma hominis or Ureaplasma urealyticum and prematurity/LBW. Twelve studies were reviewed: nine cohort studies, two case-control studies, and one randomized clinical trial of treatment. The overall isolation rate of M hominis from the genital tract was 27.2%, whereas that of U urealyticum was 70.4% (cohort studies). Results from the randomized clinical trial showed that treatment did not alter the rate of prematurity in women carrying mycoplasma species in the genital tract. None of the cohort studies supported an association between genital colonization with U urealyticum and prematurity/LBW. Similarly, no association between M hominis and prematurity/LBW could be demonstrated in seven of the eight and in six of the eight cohort studies, respectively. On the other hand, two case-control studies showed an association between U urealyticum colonization and prematurity without an association with M hominis. We conclude that the weight of the evidence does not support an association between genital colonization with mycoplasma species and prematurity/LBW.

Cohort Studies↗