Browsing by Subject "Chlamydia trachomatis"

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  • Vanic, Zeljka; Rukavina, Zora; Manner, Suvi; Fallarero, Adyary; Uzelac, Lidija; Kralj, Marijeta; Klaric, Daniela Amidzic; Bogdanov, Anita; Raffai, Timea; Virok, Dezso Peter; Filipovic-Grcic, Jelena; Skalko-Basnet, Natasa (2019)
    Background: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.
  • Joraholmen, May Wenche; Johannessen, Mona; Gravningen, Kirsten; Puolakkainen, Mirja; Acharya, Ganesh; Basnet, Purusotam; Skalko-Basnet, Natasa (2020)
    Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infections and causes serious reproductive tract complications among women. The limitations of existing oral antibiotics and treatment of antimicrobial resistance require alternative treatment options. We are proposing, for the first time, the natural polyphenol resveratrol (RES) in an advanced delivery system comprising liposomes incorporated in chitosan hydrogel, for the localized treatment of C. trachomatis infection. Both free RES and RES liposomes-in-hydrogel inhibited the propagation of C. trachomatis in a concentration-dependent manner, assessed by the commonly used in vitro model comprising McCoy cells. However, for lower concentrations, the anti-chlamydial effect of RES was enhanced when incorporated into a liposomes-in-hydrogel delivery system, with inhibition of 78% and 94% for 1.5 and 3 mu g/mL RES, respectively for RES liposomes-in-hydrogel, compared to 43% and 72%, respectively, for free RES. Furthermore, RES liposomes-in-hydrogel exhibited strong anti-inflammatory activity in vitro, in a concentration-dependent inhibition of nitric oxide production in the LPS-induced macrophages (RAW 264.7). The combination of a natural substance exhibiting multi-targeted pharmacological properties, and a delivery system that provides enhanced activity as well as applicability for vaginal administration, could be a promising option for the localized treatment of C. trachomatis infection.
  • Hiltunen-Back, Eija; Puolakkainen, Mirja (2018)
    Tippuritartunnat ovat lisääntyneet. Niitä ei voi kliinisesti erottaa klamydia- tartunnoista. Oireettomuus on yleistä kummassakin taudissa. Ne tulee testata yhtä aikaa. Genitaalialueen klamydiainfektio hoidetaan atsitromysiinillä tai doksisykliinillä ja… genitaalialueen ulkopuoliset infektiot doksisykliinillä. Tippurin hoito toteutetaan herkkyysmäärityksen mukaan. Viljelyn merkitys diagnostiikassa korostuu.
  • Rantsi, Tiina; Öhman, Hanna; Puolakkainen, Mirja; Bloigu, Aini; Paavonen, Jorma; Surcel, Heljä-Marja; Tiitinen, Aila; Joki-Korpela, Päivi (2018)
    Problem: The accuracy of Chlamydia trachomatis antibody test in predicting tubal factor infertility (TFI) is limited, and more accurate methods are needed. Cell-mediated immune response (CMI) is crucial in the resolution of pathogen, but it may play an important role in the pathogenesis of C trachomatis-associated tubal damage. We studied whether combining the markers of C trachomatis-induced CMI to humoral immune response improves the accuracy of serology in TFI prediction. Method of study: Our prospective study consists of 258 subfertile women, of whom 22 (8.5%) had TFI. Women with other causes for subfertility served as a reference group. Serum C trachomatis major outer membrane protein (MOMP) and chlamydial heat-shock protein 60 (cHSP60) IgG antibodies were measured by ELISA. CMI was studied by lymphocyte proliferation assay in vitro. Results: Serological markers were more prevalent in women with TFI than in other subfertile women (40.9% vs 12.3% for MOMP IgG and 27.3% vs 10.2% for cHSP60 IgG). The best test combination for TFI was C. trachomatis MOMP and cHSP60 antibody with an accuracy of 90.3%, sensitivity of 22.7% and specificity of 96.6%. Positive post-test probability of this combination was 54.2%, and negative post-test probability was 12.4%. Adding of the markers of CMI did not significantly improve the accuracy of serology in TFI prediction. Conclusion: The accuracy of TFI prediction increases when the combination of C trachomatis MOMP and cHSP60 antibody tests is used. C trachomatis-induced CMI was common in our study population, but the markers of CMI did not predict TFI.
  • Rantsi, Tiina; Land, Jolande A.; Joki-Korpela, Päivi; Ouburg, Sander; Hokynar, Kati; Paavonen, Jorma; Tiitinen, Aila; Puolakkainen, Mirja (2019)
    Chlamydia trachomatis IgG antibody testing (CAT) has been used as a screening test for tubal factor infertility (TFI), but as the CAT is only a marker of a past exposure to C. trachomatis and not of late sequelae, the positive predictive value (PPV) of the test is low. The persistence of C. trachomatis in the upper genital tract has been suggested as one of the key mechanisms in the development of TFI. Serum antibodies against C. trachomatis TroA and HtrA, proteins expressed specifically during persistent infection, have been suggested as novel biomarkers for TFI diagnostics. We studied serum IgG antibody responses against C. trachomatis TroA, HtrA and MOMP in 79 subfertile women, of whom 28 had laparoscopically proven TFI. We confirmed that the accuracy of CAT in diagnosing TFI is low, whereas TroA IgG and HtrA IgG are more accurate tests in detecting tubal occlusion and pelvic adhesions. However, the sensitivity and negative predictive value (NPV) of TroA IgG and HtrA IgG are still too low to justify their use as a screening test in clinical practice. Individual immunogenetic profiles combined with TroA and HtrA antibody responses might identify women with the highest risk for developing late complications after C. trachomatis infection.
  • Räsänen, Janne; Hiltunen-Back, Eija; Puolakkainen, Mirja; Pasternack, Rafael (2020)
    Lymphogranuloma venereum (LGV) on Chlamydia trachomatiksen genotyyppien L1–L3 aiheuttama seksitauti. Se voi aiheuttaa nivusimusolmukkeiden kivuliaan tulehduksen lisäksi akuutin proktiitin eli peräsuolitulehduksen. LGV-proktiitti voi muistuttaa kliiniseltä kuvaltaan ja histologiselta löydökseltään tulehduksellista suolisto¬sairautta (IBD). Kuvaamme kolme potilastapausta, joissa kaikissa pitkittyneen peräsuolivaivan taustalta löytyi lymphogranuloma venereum.
  • Brunham, Robert C.; Paavonen, Jorma (2020)
    Gynecological and obstetrical infectious diseases are an important component of women's health. A system approach to gynecological and obstetrical infection helps unify and classify microbial etiology and pathogenesis within a clinical anatomical framework of lower and upper genital tract syndromes. The reproductive system of women includes the vulva, vagina, cervix, uterus, fallopian tubes and ovaries. During pregnancy, additional tissues include the chorioamnion and placenta together with the fetus and amniotic fluid. We review in two parts reproductive system infection syndromes in women using selected research results to illustrate the clinical utility of the system approach in terms of diagnosis, treatment and prevention. We conclude that a reproductive system perspective will lead to improvements in understanding, management and prevention of these diseases.
  • Brunham, Robert C.; Paavonen, Jorma (2020)
    Lower genital tract infection and bloodborne spread of infection are the two principal modes for infection of the upper genital tract or for infection of the fetus, neonate or infant. Treponema pallidum and human immunodeficiency virus (HIV) are the two most common bloodborne pathogens that infect the fetus, neonate or infant. Most infections of the upper genital tract, however, spread along epithelial surfaces from the vagina or cervix to the upper genital tract or chorioamnion, fetus, neonate or infant. These infections are caused by either pathogens associated with a dysbiotic vaginal microbiome or those that are sexually transmitted. The clinical syndromes that these pathogens produce in the lower genital tract were discussed in part one of this review. We now discuss the syndromes and pathogens that affect the upper genital tract of both non-pregnant and pregnant women as well as fetus, neonate and infant.
  • Unemo, Magnus; Hansen, Marit; Hadad, Ronza; Puolakkainen, Mirja; Westh, Henrik; Rantakokko-Jalava, Kaisu; Thilesen, Carina; Cole, Michelle J; Boiko, Iryna; Lan, Pham T; Golparian, Daniel; Ito, Shin; Sundqvist, Martin (BioMed Central, 2020)
    Abstract Background Four new variants of Chlamydia trachomatis (nvCTs), detected in several countries, cause false-negative or equivocal results using the Aptima Combo 2 assay (AC2; Hologic). We evaluated the clinical sensitivity and specificity, as well as the analytical inclusivity and exclusivity of the updated AC2 for the detection of CT and Neisseria gonorrhoeae (NG) on the automated Panther system (Hologic). Methods We examined 1004 clinical AC2 samples and 225 analytical samples spiked with phenotypically and/or genetically diverse NG and CT strains, and other potentially cross-reacting microbial species. The clinical AC2 samples included CT wild type (WT)-positive (n = 488), all four described AC2 diagnostic-escape nvCTs (n = 170), NG-positive (n = 214), and CT/NG-negative (n = 202) specimens. Results All nvCT-positive samples (100%) and 486 (99.6%) of the CT WT-positive samples were positive in the updated AC2. All NG-positive, CT/NG-negative, Trichomonas vaginalis (TV)-positive, bacterial vaginosis-positive, and Candida-positive AC2 specimens gave correct results. The clinical sensitivity and specificity of the updated AC2 for CT detection was 99.7 and 100%, respectively, and for NG detection was 100% for both. Examining spiked samples, the analytical inclusivity and exclusivity were 100%, i.e., in clinically relevant concentrations of spiked microbe. Conclusions The updated AC2, including two CT targets and one NG target, showed a high sensitivity, specificity, inclusivity and exclusivity for the detection of CT WT, nvCTs, and NG. The updated AC2 on the fully automated Panther system offers a simple, rapid, high-throughput, sensitive, and specific diagnosis of CT and NG, which can easily be combined with detection of Mycoplasma genitalium and TV.
  • Unemo, Magnus; Hansen, Marit; Hadad, Ronza; Puolakkainen, Mirja; Westh, Henrik; Rantakokko-Jalava, Kaisu; Thilesen, Carina; Cole, Michelle J.; Boiko, Iryna; Lan, Pham T.; Golparian, Daniel; Ito, Shin; Sundqvist, Martin (2020)
    Background Four new variants ofChlamydia trachomatis(nvCTs), detected in several countries, cause false-negative or equivocal results using the Aptima Combo 2 assay (AC2; Hologic). We evaluated the clinical sensitivity and specificity, as well as the analytical inclusivity and exclusivity of the updated AC2 for the detection of CT andNeisseria gonorrhoeae(NG) on the automated Panther system (Hologic). Methods We examined 1004 clinical AC2 samples and 225 analytical samples spiked with phenotypically and/or genetically diverse NG and CT strains, and other potentially cross-reacting microbial species. The clinical AC2 samples included CT wild type (WT)-positive (n = 488), all four described AC2 diagnostic-escape nvCTs (n = 170), NG-positive (n = 214), and CT/NG-negative (n = 202) specimens. Results All nvCT-positive samples (100%) and 486 (99.6%) of the CT WT-positive samples were positive in the updated AC2. All NG-positive, CT/NG-negative,Trichomonas vaginalis(TV)-positive, bacterial vaginosis-positive, andCandida-positive AC2 specimens gave correct results. The clinical sensitivity and specificity of the updated AC2 for CT detection was 99.7 and 100%, respectively, and for NG detection was 100% for both. Examining spiked samples, the analytical inclusivity and exclusivity were 100%, i.e., in clinically relevant concentrations of spiked microbe. Conclusions The updated AC2, including two CT targets and one NG target, showed a high sensitivity, specificity, inclusivity and exclusivity for the detection of CT WT, nvCTs, and NG. The updated AC2 on the fully automated Panther system offers a simple, rapid, high-throughput, sensitive, and specific diagnosis of CT and NG, which can easily be combined with detection ofMycoplasma genitaliumand TV.
  • Rantsi, T.; Joki-Korpela, P.; Hokynar, K.; Kalliala, I.; Öhman, H.; Surcel, H-M.; Paavonen, J.; Tiitinen, A.; Puolakkainen, M. (2018)
    Persistent genital chlamydial infection may lead to tubal factor infertility (TFI). Chlamydia trachomatis TroA and HtrA are proteins expressed during persistent chlamydial infection in vitro. We studied serum IgG antibody response against these proteins by EIA in women with TFI and in subfertile women without tubal pathology. Altogether, 22 of 258 subfertile women (8.5%) had TFI which was unilateral in 17 cases and bilateral in 5 cases. Overall, 55 (21.3%) of the 258 women had TroA and 39 (15.1%) had HtrA antibodies. Seropositivity to TroA and HtrA was more common among women with TFI than women with other causes for subfertility (45.5 vs. 19.1%, p = 0.004 for TroA; 36.4 vs. 13.1%, p = 0.004 for HtrA). Mean absorbance values and the prevalence of TroA and HtrA antibodies increased with increasing severity of TFI. On the basis of our results, TroA and HtrA serology has the potential to be further developed to a specific biomarker for C. trachomatis-related TFI.
  • Korhonen, Suvi; Hokynar, Kati; Mannonen, Laura; Paavonen, Jorma; Hiltunen-Back, Eija; Puolakkainen, Mirja (2019)
    The transcriptional gene expression patterns of Chlamydia trachomatis have mainly been studied using reference strains propagated in cultured cells. Here, using five low-passage-number C. trachomatis clinical isolates that originated from asymptomatic or symptomatic female patients, the in vitro expression of the ompA, cpaf, tarp, and tox genes was studied with reverse transcriptase real-time PCR during the chlamydial developmental cycle. We observed dissimilarities in the gene expression patterns between the low-passage-number clinical isolates and the reference strains. The expression of ompA and the peak of the tox expression were observed earlier in the reference strains than in most of the clinical isolates. The expression of cpaf was high in the reference strains compared with the clinical isolates at the mid-phase (6-24 hours post infection) of the developmental cycle. All of the strains had a rather similar tarp expression profile. Four out of five clinical isolates exhibited slower growth kinetics compared with the reference strains. The use of low-passage-number C. trachomatis clinical isolates instead of reference strains in the studies might better reflect the situation in human infection.