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Carolyn M Black

Publications and source records attributed to Carolyn M Black.

At least 19 recordsLinked to original sources
PubMed2006

Population-based genetic epidemiologic analysis of Chlamydia trachomatis serotypes and lack of association between ompA polymorphisms and clinical phenotypes.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases worldwide. Urogenital strains are classified into serotypes and genotypes based on the major outer membrane protein and its gene, ompA, respectively. Studies of the association of serotypes with clinical signs and symptoms have produced conflicting results while no studies have evaluated associations with ompA polymorphisms. We designed a population-based cross-sectional study of 344 men and women with urogenital chlamydial infections (excluding co-pathogen infections) presenting to clinics serving five U.S. cities from 1995 to 1997. Signs, symptoms and sequelae of chlamydial infection (mucopurulent cervicitis, vaginal or urethral discharge; dysuria; lower abdominal pain; abnormal vaginal bleeding; and pelvic inflammatory disease) were analyzed for associations with serotype and ompA polymorphisms. One hundred and fifty-three (44.5%) of 344 patients had symptoms consistent with urogenital chlamydial infection. Gender, reason for visit and city were significant independent predictors of symptom status. Men were 2.2 times more likely than women to report any symptoms (P=0.03) and 2.8 times more likely to report a urethral discharge than women were to report a vaginal discharge in adjusted analyses (P=0.007). Differences in serotype or ompA were not predictive except for an association between serotype F and pelvic inflammatory disease (P=0.046); however, the number of these cases was small. While there was no clinically prognostic value associated with serotype or ompA polymorphism for urogenital chlamydial infections except for serotype F, future studies might utilize multilocus genomic typing to identify chlamydial strains associated with clinical phenotypes.

Adolescent↗
PubMed2006

Effect of specimen order on Chlamydia trachomatis and Neisseria gonorrhoeae test performance and adequacy of Papanicolaou smear.

STUDY OBJECTIVE: To evaluate the effect of specimen collection order on the performance of diagnostic tests for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC), and the specimen adequacy of ThinPrep Papanicolaou (Pap) smears. DESIGN: Prospective cohort study. SETTING: Public adolescent clinic. POPULATION: 313 women. INTERVENTIONS: The order of five cervical testing specimens was randomized for (1) ligase chain reaction (LCR) and (2) polymerase chain reaction (PCR) for both CT and GC; (3) transcription-mediated amplification (TMA) for CT; (4) culture for CT; and (5) cytology and LCR for GC and CT performed on ThinPrep Pap specimens. For CT and GC, a reference standard was based on three different tests performed on separate specimens. Generalized estimating equations were used to account for repeated measures. MAIN OUTCOME MEASURE: Sensitivity and specificity of diagnostic tests. RESULTS: The proportion of inadequate Pap smears was independent of specimen order. As a group, nucleic acid amplification test (NAAT) sensitivity and specificity for GC and CT were similar in the first two (early) and last three (late) swabs. Although point estimates for sensitivity were higher in the early swabs compared to the late swabs for GC LCR (13% difference), GC PCR (13%), and CT TMA (10%), these differences were not statistically significant. Their clinical significance warrants further investigation. CONCLUSIONS: In clinical settings where both Pap smears and STI testing are performed in adolescents, clinical considerations can influence the order of specimen collection, since neither Pap specimen adequacy nor test performance of NAAT for CT and GC were significantly associated with swab order.

Adolescent↗
PubMed2006

Incorporating adolescent females' perceptions of their partners' attitudes toward condoms into a model of female adolescent condom use.

The highest rates of sexually transmitted infections in the U.S. occur among adolescent females. One prevention strategy promoted for sexually active adolescents is condom use: therefore, influences on correct and consistent condom use are worth examining. Because interventions and observational research into predicting and increasing condom use have yielded mixed results, we hypothesized that a theoretically driven model incorporating female adolescents' perceptions about partner sentiments along with their own perceptions, intentions, and behaviours would improve condom use predictions. We also measured condom use errors and consistency for a more precise estimate of effective use than is common in the literature. In three structural equation models tested on a sample of 519 female adolescents, we found that intentions were associated with both correct and consistent condom use; that females' expectancy beliefs about condom use were associated with intentions; and that females' expectancy beliefs about partners' sentiments reduced the impact of their expectancy beliefs about condom use. The implications of these relations upon condom use correctness and consistency are discussed with respect to informing interventions, among other future research.

Adolescent↗
PubMed2005

Association of Chlamydia trachomatis with persistence of high-risk types of human papillomavirus in a cohort of female adolescents.

Human papillomavirus (HPV) infection is a necessary but not sufficient cause of cervical cancer. While chlamydia infection has been associated with cervical cancer, the meaning of this association remains unclear. The authors' objective was to investigate this association by evaluating whether concurrent genital tract infections are associated with HPV persistence, a precursor to cervical cancer. Interview data and biologic samples for HPV, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis testing were collected from female adolescents in an Atlanta, Georgia, longitudinal cohort study at 6-month visits (1999-2003). Associations with persistence (detection of the same HPV type at two sequential visits (visit pair)) were assessed among subjects with 2-5 visits and > or =6 months of follow-up. Associations were evaluated by logistic regression using methods for correlated data. Type-specific persistence of high-risk HPV types was detected in 77 of 181 (43%) analyzed visit pairs. Concurrent infection with C. trachomatis was independently associated with persistence of high-risk HPV types (adjusted odds ratio = 2.1, 95% confidence interval: 1.0, 4.1). Infection with more than one HPV type at the initial visit was also associated with high-risk persistence (adjusted odds ratio = 2.8, 95% confidence interval: 1.6, 4.9). The association between chlamydia infection and cervical cancer may be due to an effect of chlamydia infection on persistence of high-risk HPV.

Adolescent↗
PubMed2005

Molecular basis for the potency of IL-10-deficient dendritic cells as a highly efficient APC system for activating Th1 response.

Identification and targeting of novel immunobiological factors that regulate the induction of Th1 cells are crucial for designing effective vaccines against certain intracellular pathogens, including Chlamydia. IL-10-deficient dendritic cells (DC) are potent APCs and effective cellular vaccines that activate a high frequency of specific Th1 cells. To elucidate the molecular basis for the potency of the IL-10-deficient APC system, we tested the hypothesis that Chlamydia Ag-primed IL-10 knockout (IL-10KO) DC are quantitatively and qualitatively distinct in their metabolic characteristics relating to T cell activation. Using a combination of RT-PCR, two-dimensional gel electrophoresis, and MALDI-TOF-based proteomics analyses, the transcriptional and translational activities of Chlamydia-pulsed DC from wild-type and IL-10KO mice were assessed. IL-10 deficiency caused early maturation and activation of pulsed DC (i.e., high CD11c, CD40, CD80, CD83, CD86, IL-1, IL-12, and the T cell-attracting chemokine CCL27/CTACK) and consequently an enhanced ability to process and present Ags for a rapid and robust T cell activation. Supporting comparative proteomics revealed further that IL-10 deficient DC possess specific immunobiological properties, e.g., the T cell-attracting chemokine CCL27/CTACK, calcium-dependent protein kinase, and the IL-1/IL-12 inducer, NKR-P1A (CD161), which differentiated them immunologically from wild-type DC that express molecules relating to anti-inflammatory, differentiative, and metabolic processes, e.g., the anti-IL-12 molecule peroxisome proliferator-activated receptor-alpha and thymidine kinase. Collectively, these results provide a molecular basis for the high Th1-activating capacity of IL-10KO APC and may provide unique immunomodulation targets when designing vaccines against pathogens controlled by T cell immunity.

Animals↗
PubMed2005

The effect of correct and consistent condom use on chlamydial and gonococcal infection among urban adolescents.

OBJECTIVE: To evaluate the relationship between self-reported correct and consistent condom use and chlamydial and gonococcal infection. DESIGN: Cross-sectional study. SETTING: An urban adolescent health care clinic. Patients A total of 509 adolescent girls tested for Chlamydia trachomatis and Neisseria gonorrhoeae infection by urine nucleic acid amplification tests. Main Outcome Measure Effect of condom use on infection rates of chlamydia and gonorrhea. Consistent condom use was defined as using condoms for every act of vaginal sex and correct use as consistent use without any of the following: beginning sex without a condom, taking it off before finishing sex, flipping it over, condom breakage, or condom slippage. RESULTS: A total of 95% of the participants were African American, with a mean age of 16.6 years. Chlamydia prevalence was 21% (105/509) and gonorrhea prevalence was 7% (36/509). Condom errors were reported by 316 (71%) of 442 participants who had reported using a condom at least once in the previous 3 months. Consistent use was reported by 176 patients (35%); however, both correct and consistent use was reported by only 80 patients (16%). After adjusting for confounders, correct and consistent use was protective for chlamydia (odds ratio, 0.4; 95% confidence interval, 0.2-1.0) and highly protective for gonorrhea (odds ratio, 0.1; 95% confidence interval, 0-0.7). CONCLUSION: Our findings indicate that assessing both correctness and consistency of use is important for evaluation of condom effectiveness.

Adolescent↗
PubMed2005

Impact of patient characteristics on performance of nucleic acid amplification tests and DNA probe for detection of Chlamydia trachomatis in women with genital infections.

The performance of nucleic acid amplified tests (NAAT) for Chlamydia trachomatis at the cervix and in urine was examined in 3,551 women, and the impacts of clinical findings (age, endocervical and urethral inflammation, menses, and gonococcal coinfection) were assessed. Ligase chain reaction (LCR) and first-generation uniplex PCR were studied relative to an unamplified DNA probe (PACE2) and to an expanded, independent diagnostic reference standard. Relative to the expanded standard, cervical or urine LCR was generally the most sensitive test in most subgroups. Increased detection by NAAT of cervical C. trachomatis over PACE2 was highest among women without mucopurulent endocervical discharge versus those with (relative increase in positivity with cervical LCR, 46%) and among women > or =20 years old versus younger women (relative increase in positivity with cervical LCR, 45%). The sensitivity of cervical PCR was highest when mucopurulent endocervical discharge was present (84%) and highest for cervical LCR when cervical gonococcal coinfection was detected (91%). Urethral inflammation was associated with higher sensitivities of urine LCR (86 compared to 70% when inflammation was absent) and PCR (82 compared to 62% when inflammation was absent). Menses had no effect on test performance. The effects of patient characteristics on test specificities were less pronounced and were closely related to observed sensitivities. These findings support expanded use of NAAT for screening and diagnosis of C. trachomatis in diverse clinical populations of women.

Adult↗
PubMed2005

Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion.

T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification of the immunogenetic factors predisposing to complication development. The chemokine receptor CCR5 is crucial for T cell activation and function since its deficiency causes suppression of T cell response. We investigated the hypothesis that the clearance of genital chlamydial infection in CCR5-deficient mice could be delayed in the short term; however, a beneficial effect could include protection against inflammation-related complications such as TFI. In a translational study in humans, we investigated the effect of a functional 32 bp deletion in the CCR5 gene on the risk of developing tubal pathology in Dutch Caucasian women with immunologic evidence [i.e., immunoglobulin G (IgG) responses] of chlamydial infection. When genitally-infected wild-type (WT) and CCR5 knockout (CCR5KO) mice were evaluated for microbiologic shedding of chlamydiae, there was a greater intensity of infection and delayed resolution in the knockout mice. However, compared to WT mice, the fertility of infected CCR5KO mice (measured by pregnancy rate) was only mildly affected in the short term and unaffected in the long term (70% vs 30% reduction in the short term, and 50 vs 0% in the long term, respectively). Immunobiologic analysis revealed that the diminished capacity of CCR5KO to control acute chlamydial infection correlated with the relatively low chemokine [interferon-inducible protein 10 (IP-10) and regulated upon activation normal cell expressed and secreted (RANTES)] and cytokine (mainly interferon-gamma and tumor necrosis factor-alpha) expression corresponding to a poor early T-helper I response. However, the reduced incidence of complications in the CCR5KO mice appears to correlate with the low activity of long term inflammatory mediators. Besides, the translational studies in humans revealed that among patients with positive anti-chlamydial IgG responses, tubal pathology correlated with a low incidence of CCR5delta32 deletion (7%), while women without tubal pathology had higher incidence of the CCR5delta32 deletion (31%) as compared to controls (19%). Thus, in mice and humans the inflammation associated with CCR5 function may predispose to development of complications of chlamydial infection, such as TFI.

Animals↗
PubMed2004

A novel recombinant multisubunit vaccine against Chlamydia.

The administration of an efficacious vaccine is the most effective long-term measure to control the oculogenital infections caused by Chlamydia trachomatis in humans. Chlamydia genome sequencing has identified a number of potential vaccine candidates, and the current challenge is to develop an effective delivery vehicle for induction of a high level of mucosal T and complementary B cell responses. Vibrio cholerae ghosts (VCG) are nontoxic, effective delivery vehicles with potent adjuvant properties, and are capable of inducing both T cell and Ab responses in mucosal tissues. We investigated the hypothesis that rVCG could serve as effective delivery vehicles for single or multiple subunit chlamydial vaccines to induce a high level of protective immunity. rVCG-expressing chlamydial outer membrane proteins were produced by a two-step genetic process, involving cloning of Omp genes in V. cholerae, followed by gene E-mediated lysis of the cells. The immunogenicity and vaccine efficacy of rVCG-expressing single and multiple subunits were compared. Immunologic analysis indicated that i.m. immunization of mice with either vaccine construct induced a strong mucosal and systemic specific Th1 response against the whole chlamydial organism. However, there was an immunogenic advantage associated with the multiple subunit vaccine that induced a higher frequency of Th1 cells and a relatively greater ability to confer protective immunity, compared with the single subunit construct. These results support the operational theory that the ability of a vaccine to confer protective immunity against Chlamydia is a function of the level of Th1 response elicited.

Animals↗
PubMed2004

Population-based genetic and evolutionary analysis of Chlamydia trachomatis urogenital strain variation in the United States.

Chlamydia trachomatis is a major cause of ocular and sexually transmitted diseases worldwide. While much of our knowledge about its genetic diversity comes from serotyping or ompA genotyping, no quantitative assessment of genetic diversity within serotypes has been performed. To accomplish this, 507 urogenital samples from a multicenter U.S. study were analyzed by phylogenetic and statistical modeling. No B, Da, or I serotypes were represented. Based on our analyses, all but one previous urogenital B serotype was identified as Ba. This, coupled with the lack of B serotypes in our population, suggests that B has specific tropism for ocular mucosa. We identified a Ba/D recombinant (putative crossover nucleotide 477; P < 0.0001) similar to a B/D mosaic we described previously from an African trachoma patient. Computational analyses of the Ba/D recombinant indicated that upstream changes were less important for tissue tropism than downstream incorporation of the D sequence. Since most serotypes had nonsynonymous/synonymous ratios of <1.0, the major outer membrane protein, encoded by ompA, has many functional constraints and is under purifying selection. Surprisingly, all serotype groups except for J had a unimodal population structure indicating rapid clonal expansion. Of the groups with a unimodal structure, E and Ia and, to a lesser extent, G and K were prevalent, had infrequent incorporation of mutations, and, compared to other groups, had a relatively greater degree of diversifying selection, consistent with a selective sweep of mutations within these groups. Collectively, these data suggest a diverse evolutionary strategy for different serogroups of the organism.

Adolescent↗
PubMed2004

Antibody regulation of Tcell immunity: implications for vaccine strategies against intracellular pathogens.

Intracellular microbial pathogens cause a plethora of diseases that pose a huge public health challenge. Efficacious prophylactic vaccines are needed to protect the population from this myriad of infectious diseases. Contemporary approaches to vaccine design are guided by the immunobiological paradigm that extracellular pathogens are controlled principally by humoral immunity, involving specific antibodies, whereas host protection against intracellular pathogens requires effectors of cell-mediated immunity. However, this distinct T-helper (Th) type 1 and 2 paradigm of host defense has encountered a major challenge due to the reality that most antigens or vaccines induce mixed immune responses comprising of both humoral and CMI effectors. Besides, the true functional independence of antibodies and T-cells under in vivo physiologic conditions is uncertain. Recent findings have revealed that antibodies exert a significant immunoregulatory effect on T-cell immunity. Thus, a robust and protective T-cell memory response against microbial pathogens such as Chlamydia and Mycobacteria require an effective primary humoral immune response characterized by specific antibody isotypes whose role is to modulate Th1 activation via Fc receptors (FcR) by facilitating a rapid uptake, processing and presentation of pathogen-derived antigens for an enhanced T-cell response. These findings have crystallized into a paradigm shift in host defense wherein different components of the apparently disparate mixed immune responses elicited against a microbial pathogen function concertedly to maximize the principal effector mechanism. This review focuses on the essential role of both arms of the immune system in controlling intracellular microbial pathogens, especially the regulatory role of FcR-mediated antibody function in optimizing the induction of a protective Th1 response. The immunobiological implications are discussed in the context of vaccine design, delivery and evaluation against intracellular microbial pathogens of bacteria, fungi and parasitic origin.

Animals↗
PubMed2004

Developing effective delivery systems for Chlamydia vaccines.

Members of the genus Chlamydia cause a plethora of ocular, genital and respiratory diseases, with severe complications, such as blinding trachoma, pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility, interstitial pneumonia, and chronic diseases that may include atherosclerosis, multiple sclerosis, adult-onset asthma and Alzheimer's disease. The current medical opinion is that an effective prophylactic vaccine would constitute the best approach to protect the human population from the most severe consequences of these infections. There are three essential and mutually inclusive areas of challenge confronting researchers developing Chlamydia vaccines. These are to define the elements of protective immunity and the basis of vaccine evaluation, the judicious selection of an immunogenic and safe antigen(s) to form the basis of a subunit vaccine, and to develop effective delivery systems that boost the immune response to achieve long-lasting protective immunity. The development of delivery vehicles and adjuvants to boost protective long-term immunity against chlamydiae currently poses the greatest challenge in vaccine research. However, enormous progress is being made in the construction of novel delivery systems, such as DNA and plasmid expression systems, viral vectors, and living and non-living bacterial delivery systems, and the use of chemical adjuvants. In addition, there is increasing effort being made in designing delivery strategies involving specific immunomodulatory procedures that modify the cytokine and chemokine environment, upregulate co-stimulatory molecules and target vaccines to specific mucosal sites. These efforts will likely culminate in an efficacious chlamydial vaccine in the near future.

Adult↗
PubMed2003

Epidemiology of human papillomavirus infection and abnormal cytologic test results in an urban adolescent population.

We determined the prevalence of and the risk factors for human papillomavirus (HPV) infection and abnormal cytologic test results in 312 adolescent girls (mean age, 16.1 years). Subjects had a median of 2 years of sexual activity and 4 lifetime sex partners. Cervical HPV was detected by use of L1-consensus polymerase chain reaction in 64% of subjects; half of those with HPV had >1 type, and 77% had >/=1 high-risk type. Independent risk factors for HPV were lifetime number of sex partners, age of partner, and douching. Cytologic abnormalities were common (20.9% of subjects had atypical squamous cells of uncertain significance, and 17.0% had high- or low-grade squamous intraepithelial lesions) and were significantly associated with detection of HPV (P=.0001); however, most (51.6%) subjects with HPV had normal cytologic test results.

Adolescent↗
PubMed2003

Fc receptor-mediated antibody regulation of T cell immunity against intracellular pathogens.

Immunity to intracellular microbial pathogens, including Chlamydia species, is controlled primarily by cell-mediated effector mechanisms, yet, the absence of antibodies results in inefficient microbial clearance. We investigated the hypothesis that certain Fc receptor functions promote the rapid induction of elevated T helper type 1 (Th1) response, which effectively clears chlamydiae. FcR(-/-) mice exhibited a delayed and reduced frequency of Chlamydia-specific Th1 cells, compared to FcR(+/+) mice. In vitro, antichlamydial antibodies increased the rate of Th1 activation by FcR(+/+) but not FcR(-/-) antigen-presenting cells. FcR(-/-) dendritic cells and the T cell-associated IgG2A and IgA mediate enhanced Th1 activation by antibodies. Immunization with chlamydia-antibody complexes induced elevated and protective Th1 response. These results provide a mechanistic basis for requiring both T cell and humoral immune responses in protective immunity and vaccine evaluation. Findings offer a paradigm in host defense wherein different effector components function indirectly to maximize the principal effector mechanism.

Animals↗
PubMed2003

Recombinant Vibrio cholerae ghosts as a delivery vehicle for vaccinating against Chlamydia trachomatis.

An efficacious vaccine is needed to control the morbidity and burden of rising healthcare costs associated with genital Chlamydia trachomatis infection. Despite considerable efforts, the development of reliable chlamydial vaccines using conventional strategies has proven to be elusive. The 40kDa major outer membrane protein (MOMP) of C. trachomatis is so far the most promising candidate for a subunit vaccine. The lack of satisfactory protective immunity with MOMP-based vaccine regimens to date would suggest that either MOMP alone is inadequate as a vaccine candidate or better delivery systems are needed to optimize the effect of MOMP. Recombinant Vibrio cholerae ghosts (rVCG) are attractive for use as non-living vaccines because they possess strong adjuvant properties and are excellent vehicles for delivery of antigens of vaccine relevance to mucosal sites. The suitability of the ghost technology for designing an anti-chlamydial vaccine was evaluated by constructing a rVCG vector-based candidate vaccine expressing MOMP (rVCG-MOMP) and assessing vaccine efficacy in a murine model of C. trachomatis genital infection. Intramuscular delivery of the rVCG-MOMP vaccine induced elevated local genital mucosal as well as systemic Th1 responses. In addition, immune T cells from immunized mice could transfer partial protection against a C. trachomatis genital challenge to nai;ve mice. These results suggest that rVCG expressing chlamydial proteins may constitute a suitable subunit vaccine for inducing an efficient mucosal T cell response that protects against C. trachomatis infection. Altogether, the potency and relatively low production cost of rVCG offer a significant technical advantage as a chlamydial vaccine.

Animals↗
PubMed2003

Comparison of methods for detection of Chlamydia trachomatis and Neisseria gonorrhoeae using commercially available nucleic acid amplification tests and a liquid pap smear medium.

Annual screening for Chlamydia trachomatis infection is currently recommended for sexually active women 15 to 25 years old and for women older than 25 if they have a new or multiple sex partners and have not used condoms during the previous 3 months. Annual screening for cervical abnormalities using the Pap smear has achieved a substantial reduction in morbidity and mortality from cervical cancer. Screening for Neisseria gonorrhoeae infection has likely contributed significantly to the reduction in the rates of gonococcal infection. The introduction of liquid Pap smear methods using exfoliated cervical cells presents an opportunity to screen for these three conditions using one specimen. We evaluated the preservation of C. trachomatis and Neisseria gonorrhoeae DNAs from ThinPrep liquid media (PreservCyt; Cytyc Corp., Boxborough, Mass.); tested the feasibility of using a clinical specimen of this medium for the detection of cytologic abnormalities, C. trachomatis, and N. gonorrhoeae; evaluated the agreement between ligase chain reaction (LCR) performed on PreservCyt and LCR performed on a cervical specimen; and compared the performance of LCR performed on PreservCyt to those of LCR performed on a cervical specimen, culture, PCR performed on a cervical specimen, on urine, and on a vaginal specimen (a multiple-site infection status standard), and transcription-mediated amplification (for C. trachomatis only) from 255 sexually active adolescent women. The agreement between LCR performed on PreservCyt and LCR from a cervical swab in LCx transport medium was high (for C. trachomatis, agreement = 0.97 and kappa = 0.92; for N. gonorrhoeae, agreement = 0.99 and kappa = 0.96). Test performances were similar for LCR-urine, LCR-cervix, and LCR-ThinPrep, with sensitivities from 93 to 99% for C. trachomatis and 81 to 83% for N. gonorrhoeae and specificities from 95.5 to 99% for C. trachomatis and 99.1 to 99.6% for N. gonorrhoeae using a PCR-based multiple-site infection status standard. This is the first study to examine the agreement between liquid cytologic media and multiple nucleic acid amplification tests for the detection of C. trachomatis and N. gonorrhoeae from patient samples. Cytologic fluid shows promise for simultaneous screening for cytologic abnormalities and sexually transmitted infections.

Adolescent↗
PubMed2003

Contemporary approaches to designing and evaluating vaccines against Chlamydia.

The clinically relevant pathologic consequences of primary ocular, genital, or respiratory human infection by members of the genus Chlamydia are conjunctivitis, cervicitis, urethritis and sinusitis. The major complications and sometimes debilitating evolutionary outcomes of these infections include: trichiasis and cicatrizing trachoma, endometritis or pelvic inflammatory disease and involuntary tubal factor infertility and bronchopulmonary pneumonia. These diseases, in addition to other chlamydia-associated chronic syndromes (e.g., artherosclerosis, multiple sclerosis and Alzheimer's disease), pose serious public healthcare and huge budgetary concerns. The current medical opinion is that an efficacious prophylactic vaccine is a sine qua non--to control the morbidity of chiamydial infection in the human population. The research goal for an efficacious human chlamydial vaccine has faced key challenges to define the elements of protective immunity to facilitate vaccine evaluation, the judicious selection of appropriate vaccine candidates that possess stable antigenic and immunologic properties and the development of effective delivery vehicles and adjuvants to boost immune effectors to achieve long-term protective immunity. Progress in the functional immunobiology of Chlamydia has established the essential immunologic paradigms for vaccine selection and evaluation, including the obligatory requirement for a vaccine to induce T-helper Type 1 immune response that controls chlamydiae. Recent advances in chlamydial genomics and proteomics should enhance the identification of likely chlamydial gene products that fulfill the antigenic requirements of putative vaccine candidates. Major inroads are however needed in the construction and development of novel and effective delivery systems, such as vectors and adjuvants. This review summarizes the status of contemporary chlamydial vaccine research and promising trends fueling the growing optimism for an efficacious vaccine. The unified approach to vaccines for the genus Chlamydia is validated by the several conserved genes and common immunogenic proteins among member species and the similarity of immune effectors controlling Chlamydia species in animals and humans.

Adjuvants, Immunologic↗