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1.  Protection of Mice From a Chlamydia trachomatis Vaginal Infection Using a Salicylidene Acylhydrazide, a Potential Microbicide 
The Journal of Infectious Diseases  2011;204(9):1313-1320.
The salicylidene acylhydrazide INP0341 inhibits growth of Chlamydia in HeLa cells, has negligible cell toxicity, and does not inhibit the growth of lactobacilli. The antichlamydial activity of INP0341 was retained when tested in vaginal and semen simulants. Vaginal tissue from INP0341-treated mice appeared similar to control sham-treated mice. To determine whether INP0341 can protect mice from a vaginal challenge, C3H/HeJ mice were either sham or INP0341 treated intravaginally pre- and postinoculation with 5 × 102 inclusion-forming units (IFUs) of Chlamydia trachomatis serovar D. Vaginal cultures taken over a month-long period showed a significant difference in the number of control mice that were culture positive versus the number in the INP0341-treated group, 100% (25/25) and 31% (8/26), respectively (P < .05). The quantity of IFUs shed and antibody titers to Chlamydia were significantly higher for the control group (P < .05). In summary, INP0341 is a promising compound to be considered for formulation as a vaginal microbicide.
doi:10.1093/infdis/jir552
PMCID: PMC3182314  PMID: 21933873
2.  Reversal of the Antichlamydial Activity of Putative Type III Secretion Inhibitors by Iron▿  
Infection and Immunity  2007;75(7):3478-3489.
INPs, which are chemically synthesized compounds belonging to a class of acylated hydrazones of salicylaldehydes, can inhibit the growth of Chlamydiaceae. Evidence has been presented that in Yersinia and Chlamydia INPs may affect the type III secretion (T3S) system. In the present study 25 INPs were screened for antichlamydial activity at a concentration of 50 μM, and 14 were able to completely inhibit the growth of Chlamydia trachomatis serovar D in McCoy and HeLa 229 cells. The antichlamydial activities of two of these INPs, INPs 0341 and 0400, were further characterized due to their low cytotoxicity. These compounds were found to inhibit C. trachomatis in a dose-dependent manner; were not toxic to elementary bodies; were cidal at a concentration of ≥20 μM; inhibited all Chlamydiaceae tested; and could inhibit the development of C. trachomatis as determined by the yield of progeny when they were added up to 24 h postinfection. INP 0341 was able to affect the expression of several T3S genes. Compared to the expression in control cultures, lcrH-1, copB, and incA, all middle- to late-expressed T3S genes, were not expressed in the INP 0341-treated cultures 24 to 36 h postinfection. Iron, supplied as ferrous sulfate, as ferric chloride, or as holo-transferrin, was able to negate the antichlamydial properties of the INPs. In contrast, apo-transferrin and other divalent metal ions tested were not able to reverse the inhibitory effect of the INPs. In conclusion, the potent antichlamydial activity of INPs is directly or indirectly linked with iron, and this inhibition of Chlamydia has an effect on the T3S system of this intracellular pathogen.
doi:10.1128/IAI.00023-07
PMCID: PMC1932962  PMID: 17470544
3.  Mutations in hemG Mediate Resistance to Salicylidene Acylhydrazides, Demonstrating a Novel Link between Protoporphyrinogen Oxidase (HemG) and Chlamydia trachomatis Infectivity 
Journal of Bacteriology  2013;195(18):4221-4230.
Salicylidene acylhydrazides (SAHs) inhibit the type III secretion system (T3S) of Yersinia and other Gram-negative bacteria. In addition, SAHs restrict the growth and development of Chlamydia species. However, since the inhibition of Chlamydia growth by SAH is suppressed by the addition of excess iron and since SAHs have an iron-chelating capacity, their role as specific T3S inhibitors is unclear. We investigated here whether SAHs exhibit a function on C. trachomatis that goes beyond iron chelation. We found that the iron-saturated SAH INP0341 (IS-INP0341) specifically affects C. trachomatis infectivity with reduced generation of infectious elementary body (EB) progeny. Selection and isolation of spontaneous SAH-resistant mutant strains revealed that mutations in hemG suppressed the reduced infectivity caused by IS-INP0341 treatment. Structural modeling of C. trachomatis HemG predicts that the acquired mutations are located in the active site of the enzyme, suggesting that IS-INP0341 inhibits this domain of HemG and that protoporphyrinogen oxidase (HemG) and heme metabolism are important for C. trachomatis infectivity.
doi:10.1128/JB.00506-13
PMCID: PMC3754756  PMID: 23852872
4.  In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds 
Introduction
Salicylidene acylhydrazide compounds have been shown to inhibit bacterial pathogens, including Chlamydia and Neisseria gonorrhoeae. If such compounds could also target HIV-1, their potential use as topical microbicides to prevent sexually transmitted infections would be considerable. We determined the in vitro anti-HIV-1 activity, cytotoxicity and mechanism of action of several salicylidene acylhydrazides.
Methods
Inhibitory activity was assessed using TZMbl cells and primary peripheral blood mononuclear cells (PBMCs) as targets for HIV-1 infection. Anti-viral activity was measured against cell-free and cell-associated virus and in vaginal fluid and semen simulants. Since the anti-bacterial activity of salicylidene acylhydrazides is reversible by Fe2+, we determined whether Fe2+ and other cations could reverse the anti-HIV-1 activity of the compounds. We also employed real-time PCR to determine the stage affected in the HIV-1 replication cycle.
Results
We identified four compounds with 50% HIV-1 inhibitory concentrations of 1 to 7 μM. In vitro toxicity varied but was generally limited. Activity was similar against three R5 clade B primary isolates and whether targets for virus replication were TZMbl cells or PBMCs. Compounds inhibited cell-free and cell-associated virus and were active in vaginal fluid and semen simulants. Fe2+, but not other cations, reversed the anti-HIV-1 effect. Finally, inhibitory effect of the compounds occurred at a post-integration step.
Conclusions
We identified salicylidene acylhydrazides with in vitro anti-HIV-1 activity in the μM range. The activity of these compounds against other sexually transmitted pathogens makes them potential candidates to formulate for use as a broad-spectrum topical genital microbicide.
doi:10.1016/j.ijantimicag.2012.05.023
PMCID: PMC3438335  PMID: 22819150
Salicylidene acylhydrazides; HIV; microbicide; iron chelation
5.  Chlamydia trachomatis Laboratory Strains versus Recent Clinical Isolates: Implications for Routine Microbicide Testing ▿  
A topical microbicide that women can use to prevent sexually transmitted diseases (STDs) is essential, and many microbicide candidates are being tested for activity against human immunodeficiency virus and other STDs, including Chlamydia trachomatis. Screening assays for assessing the activity of microbicides against C. trachomatis are typically done with laboratory-adapted strains, but it is possible that recent clinical isolates may have different susceptibilities to microbicides, as has been seen with Neisseria gonorrhoeae and Lactobacillus spp. (B. J. Moncla and S. L. Hillier, Sex. Transm. Dis. 32:491-494, 2005). We utilized three types of microbicides to help define this aspect of our assay to test microbicides against C. trachomatis in vitro. To simulate conditions of transmission, we used an assay that we previously developed in which we exposed chlamydial elementary bodies to microbicides prior to contact with epithelial cells. We first determined the toxicity of microbicides to the cells used to culture Chlamydia trachomatis in the assay and, if necessary, modified the assay to eliminate toxicity at the concentrations tested. We compared the sensitivities of recent clinical isolates of Chlamydia trachomatis versus laboratory strains of the same serovar and found major differences in sensitivity to nonoxynol-9 (non-9), but only minor differences were seen with the other microbicides. We thus conclude that when assessing activity of potential topical microbicides versus the obligate intracellular bacteria C. trachomatis, the use of recent clinical isolates may not be necessary to draw a conclusion about a microbicide's effectiveness. However, it is important to keep in mind that differences (like those seen with non-9) are possible and that clinical isolates could be included in later stages of testing.
doi:10.1128/AAC.01179-08
PMCID: PMC2663080  PMID: 19188383
6.  Hydrogels containing monocaprin have potent microbicidal activities against sexually transmitted viruses and bacteria in vitro 
Sexually Transmitted Infections  1999;75(3):181-185.
OBJECTIVE: To investigate the in vitro microbicidal and cytocidal potency of monocaprin dissolved in pharmaceutical hydrogel formulations and to evaluate their potential use as vaginal microbicides against sexually transmitted pathogens such as herpes simplex virus type 2 (HSV-2), human immunodeficiency virus type 1 (HIV-1), Chlamydia trachomatis, and Neisseria gonorrhoeae. METHODS: Gel formulations were mixed with equal volumes of virus/bacteria suspensions in culture medium and incubated for 1 and 5 minutes. The reduction in virus/bacteria titre was used as a measure of microbicidal activity. Similarly, gels were mixed with human semen to study their effect on leucocytes. The toxicity of the gels was tested in rabbits by the standard vaginal irritation test. RESULTS: Gels containing 20 mM of monocaprin caused a greater than 100,000-fold inactivation of HSV-2 and Neisseria in 1 minute and of Chlamydia in 5 minutes. Similarly, the gels caused a greater than 10,000-fold inactivation of HIV-1 in semen in 1 minute. They caused more than a 10,000-fold reduction in the number of viable leucocytes in semen in 1 minute. No toxic effect on the vaginal mucosa of rabbits was observed after daily exposure for 10 days. CONCLUSIONS: Hydrogels containing monocaprin are potent inactivators of sexually transmitted viruses and bacteria in vitro. This simple lipid seems to be a feasible choice as a mucosal microbicide for prevention of sexually transmitted infections. It is a natural compound found in certain foodstuffs such as milk and is therefore unlikely to cause harmful side effects in the concentrations used. 



PMCID: PMC1758207  PMID: 10448397
7.  Phenotypic and genetic characterisation of bacterial sexually transmitted infections in Bissau, Guinea-Bissau, West Africa: a prospective cohort study 
BMJ Open  2012;2(2):e000636.
Background
Knowledge regarding characteristics and transmission of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium and antibiotic resistance in N gonorrhoeae in Guinea-Bissau, West Africa, is entirely lacking.
Objectives
To characterise N gonorrhoeae, C trachomatis and M genitalium samples from Guinea-Bissau and to define bacterial populations, possible transmission chains and for N gonorrhoeae spread of antibiotic-resistant isolates.
Design
Prospective cohort study.
Setting
Two sexual health and family planning clinics, Bissau, Guinea-Bissau.
Participants
Positive samples from 711 women and 27 men.
Material and methods
Positive samples for N gonorrhoeae (n=31), C trachomatis (n=60) and M genitalium (n=30) were examined. The gonococcal isolates were characterised with antibiograms, serovar determination and N gonorrhoeae multiantigen sequence typing (NG-MAST). The C trachomatis ompA gene and the M genitalium mgpB gene were sequenced, and phylogenetic analyses were performed.
Results
For N gonorrhoeae, the levels of resistance (intermediate susceptibility) to ciprofloxacin, erythromycin, rifampicin, ampicillin, tetracycline, penicillin G and cefuroxime were 10% (0%), 6% (10%), 13% (10%), 68% (0%), 74% (0%), 68% (16%) and 0% (84%), respectively. All isolates were susceptible to cefixime, ceftriaxone, spectinomycin and azithromycin, and the minimum inhibitory concentrations of kanamycin (range: 8–32 mg/l) and gentamicin (range: 0.75–6 mg/l) were low (no resistance breakpoints exist for these antimicrobials). 19 NG-MAST sequence types (STs) (84% novel STs) were identified. Phylogenetic analysis of the C trachomatis ompA gene revealed genovar G as most prevalent (37%), followed by genovar D (19%). 23 mgpB STs were found among the M genitalium isolates, and 67% of isolates had unique STs.
Conclusions
The diversity among the sexually transmitted infection (STI) pathogens may be associated with suboptimal diagnostics, contact tracing, case reporting and epidemiological surveillance. In Guinea-Bissau, additional STI studies are vital to estimate the STI burden and form the basis for a national sexual health strategy for prevention, diagnosis and surveillance of STIs.
Article summary
Article focus
Knowledge regarding characteristics and transmission of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium and antibiotic resistance in N gonorrhoeae in Guinea-Bissau, West Africa, is entirely lacking.
We aimed to phenotypically and genetically characterise N gonorrhoeae, and genetically characterise C trachomatis and M genitalium samples from women attending two sexual health clinics in Bissau, Guinea-Bissau and to define the bacterial populations, possible transmission chains and for N gonorrhoeae also to define the presence and spread of antibiotic-resistant isolates from women and additionally a group of symptomatic men.
Key messages
In Guinea-Bissau, N gonorrhoeae isolates displayed high level of resistance to traditional gonorrhoea antimicrobials but have remained susceptible to extended-spectrum cephalosporins, spectinomycin and azithromycin.
Genovar G, D and F were the most prevalent C trachomatis genovars, the usually most common genovar among heterosexuals, that is, genovar E, was rare.
The diversity among the bacterial STI pathogens may be associated with suboptimal diagnostics, contact tracing, case reporting and epidemiological surveillance. Additional studies are vital to estimate the STI burden and form the basis for a national sexual health strategy for prevention, diagnosis and surveillance.
Strengths and limitations of this study
This is the first time N gonorrhoeae, C trachomatis and M genitalium samples from Bissau, Guinea-Bissau, have been phenotypically and genetically characterised to define the bacterial populations, possible transmission chains and antibiotic resistance in N gonorrhoeae.
The study sample was relatively small, and in this setting, it is difficult to perform appropriate sample transportation and storage, as well as optimised diagnostics, which may have resulted in that true-positive samples were lost.
doi:10.1136/bmjopen-2011-000636
PMCID: PMC3329603  PMID: 22436137
8.  Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by Strand Displacement Amplification and Relevance of the Amplification Control for Use with Vaginal Swab Specimens 
Journal of Clinical Microbiology  2003;41(8):3592-3596.
Vaginal swab specimens may be preferable to cervical swab or urine specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae because of the ease of specimen collection and transport. The purpose of this study was to evaluate whether vaginal swab specimens are equivalent to cervical swab specimens for the detection of N. gonorrhoeae and C. trachomatis by the Becton Dickinson strand displacement amplification assay (SDA) with the BDProbeTec ET instrument and then to evaluate the use of the amplification control in a clinical research setting. In the first phase, vaginal and cervical swab specimens were obtained from 455 symptomatic women aged 18 to 40 attending primary health care and sexually transmitted disease clinics. Thirty-nine specimens (8.6%) had true-positive results for N. gonorrhoeae and 37 specimens (8.1%) had true-positive results for C. trachomatis. The sensitivity of SDA was superior to that of culture for the detection of N. gonorrhoeae with vaginal swab specimens and equivalent to that of the Roche PCR for the detection of C. trachomatis with cervical swab specimens. In the second phase of the study, 1,411 consecutively collected vaginal swab specimens were evaluated, with 357 (25.3%) specimens giving indeterminate readings on the basis of the result for the amplification control. The prevalences of sexually transmitted pathogens in vaginal swab specimens with and without use of the amplification control were 6.0 and 5.8%, respectively, for C. trachomatis and 3.1 and 3.0%, respectively, for N. gonorrhoeae. Although, vaginal swab specimens were equivalent to cervical swab specimens for the detection of N. gonorrhoeae and C. trachomatis by SDA with respect to sensitivity, one in four vaginal swab specimens yielded an indeterminate result when the amplification control was used. The amplification control has limited value for use with vaginal swab specimens.
doi:10.1128/JCM.41.8.3592-3596.2003
PMCID: PMC179790  PMID: 12904360
9.  Syndromic management of vaginal discharge among women in a reproductive health clinic in India 
Sexually Transmitted Infections  2000;76(4):303-306.
Objectives: To examine the performance of the syndromic approach in the management of vaginal discharge among women attending a reproductive health clinic in New Delhi, India.
Methods: Women who sought services from the clinic and who had a complaint of vaginal discharge were interviewed, underwent a pelvic examination, and provided samples for laboratory investigations of bacterial vaginosis, candidiasis, syphilis, trichomoniasis, and Chlamydia trachomatis and Neisseria gonorrhoeae infections. Data analysis focused on the prevalence of infection and on the performance of the algorithm recommended by the national authorities for the management of vaginal discharge.
Results: The most common infection among 319 women was bacterial vaginosis (26%). At least one sexually transmitted infection was detected in 21.9% of women. The prevalence of C trachomatis infection was 12.2%; trichomoniasis 10%; syphilis 2.2%; N gonorrhoeae was not isolated. An algorithm based on risk assessment and speculum assisted clinical evaluation was not helpful in predicting cervical infections associated with C trachomatis (sensitivity 5% and PPV 9%). This algorithm was sensitive (95%) though not specific (22%) in selecting women for metronidazole therapy effective against bacterial vaginosis or trichomoniasis, and overtreatment was a problem (PPV 38%). The sensitivity, specificity, and PPV of this algorithm for the treatment of candidiasis were 46%, 98%, and 88% respectively. The cost per case assessed using the algorithm was $2 and the cost per infection correctly treated was $4.25.
Conclusions: The prevalence of cervical infection associated with C trachomatis was high among these "low risk" women. The syndromic approach is not an efficient tool for detecting this condition, and alternative approaches to evaluation and intervention are required. The syndromic management of vaginal discharge among women seeking family planning and other reproductive health services should focus on vaginal infections, thus enhancing quality of care and addressing women's concerns about their health.
Key Words: syndromic approach; vaginal discharge; Chlamydia trachomatis; reproductive health; India
doi:10.1136/sti.76.4.303
PMCID: PMC1744180  PMID: 11026889
10.  Killing of Chlamydia trachomatis by Novel Antimicrobial Lipids Adapted from Compounds in Human Breast Milk 
The development of new methods for prevention of sexually transmitted Chlamydia trachomatis infection is a top public health priority. Topical self-administered vaginal microbicides represent one such approach in which the organism is eradicated at the time of initial exposure. To this end, we examined the activity of five synthetic lipids adapted from naturally occurring compounds found in human breast milk. C. trachomatis serovar D or F elementary bodies were added to serial dilutions of the lipids and incubated for various times. Aliquots were then cultured in monolayers of McCoy cells, and inclusions were counted. A 7.5 mM concentration of 2-O-octyl-sn-glycerol completely prevented growth of C. trachomatis after 120 min of contact with the organism. The remaining lipids, 1-O-octyl-, 1-O-heptyl-, 2-O-hexyl-, and 1-O-hexyl-sn-glycerol, showed less activity. On electron microscopic examination, the lipids were shown to have disrupted the chlamydial inner membrane, allowing leakage of the cytoplasmic contents from the cell. Lipid activity was unaffected by the presence of 10% human blood or alterations in pH from 4.0 to 8.0, conditions reflecting those sometimes found in the vagina. Our results suggest that these lipids, especially 2-O-octyl-sn-glycerol, may be effective as topical microbicides in preventing the transmission of C. trachomatis. Further efficacy and toxicity studies with these lipids and assessment of their activity against other sexually transmitted disease pathogens are in progress.
PMCID: PMC105787  PMID: 9593157
11.  Comparison of Methods for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae Using Commercially Available Nucleic Acid Amplification Tests and a Liquid Pap Smear Medium 
Journal of Clinical Microbiology  2003;41(4):1507-1511.
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.
doi:10.1128/JCM.41.4.1507-1511.2003
PMCID: PMC153886  PMID: 12682137
12.  Comparing First-Void Urine Specimens, Self-Collected Vaginal Swabs, and Endocervical Specimens To Detect Chlamydia trachomatis and Neisseria gonorrhoeae by a Nucleic Acid Amplification Test 
Journal of Clinical Microbiology  2003;41(9):4395-4399.
We set out to determine the prevalences of Chlamydia trachomatis and Neisseria gonorrhoeae by ligase chain reaction as well as to determine the prevalence of Trichomonas vaginalis by culture in a large and diverse national sample of non-health-care-seeking young women entering the military; we also sought to compare the abilities of three different techniques of collecting specimens (first-void urine, self-collected vaginal swab, and clinician-collected endocervical swab) to identify a positive specimen. A cross-sectional sample of young women was voluntarily recruited; as a part of their routine entry pelvic examination visit, they completed a self-administered reproductive health questionnaire and provided first-void urine (used to detect C. trachomatis and N. gonorrhoeae) and self-collected vaginal swabs (used to detect C. trachomatis, N. gonorrhoeae, and T. vaginalis). The number of positive tests divided by the number of sexually active women screened by each sampling method determined the rates of prevalence. The rate of infection with any of the three sexually transmitted diseases (STDs) tested was 14.1%. The total positive rates for each STD (identified by ≥1 specimen) were the following: for C. trachomatis, 11.6%; N. gonorrhoeae, 2.4%; and T. vaginalis, 1.7%. The proportions of positives identified by specimen type were, for C. trachomatis and N. gonorrhoeae, respectively, endocervix, 65 and 40%; urine, 72 and 24%; and vagina, 81 and 72%. The proportions of positives when specimen results were combined were, for C. trachomatis and N. gonorrhoeae, respectively, cervix plus urine, 86 and 49%; cervix plus vagina, 91 and 93%; and vagina plus urine, 94 and 79%. We concluded that STDs were epidemic in this population. Self-collected vaginal swabs identified the highest number of positive test results among single specimens, with the combined cervix-vagina results identifying the highest number of positive results. Self-collected vaginal swab collections are a feasible alternative to cervical specimen collections in this population, and the use of multiple types of specimens increases the positive yield markedly.
doi:10.1128/JCM.41.9.4395-4399.2003
PMCID: PMC193832  PMID: 12958275
13.  Screening of pregnant women attending the antenatal care clinic of a tertiary hospital in eastern Saudi Arabia for Chlamydia trachomatis and Neisseria gonorrhoeae infections 
Inroduction:
Of the “top ten” sexually transmitted infections, Chlamydia trachomatis and Neisseria gonorrhoeae are ranked second and fifth, respectively, worldwide.
Aim:
The aim of this study was to screen the pregnant women for C. trachomatis and N. gonorrhoeae infections and to detect antimicrobial resistance pattern of N. gonorrhoeae.
Materials and Methods:
This study was a prospective, hospital-based analysis of a random sample of pregnant women visiting the antenatal clinic of a tertiary hospital in eastern Saudi Arabia. Endocervical and high vaginal swabs were collected both from pregnant women and female patients attending gynecology clinic with lower genital tract infection (control group). C. trachomatis antigen was detected using enzyme-linked immunosorbent assay (ELISA). N. gonorrhoeae was detected by culture and identification of isolates, and antimicrobial susceptibility testing was performed. Statistical Package for Social Sciences (SPSS) version 13.0 and Chi-square test were used for statistical analysis.
Results:
C. trachomatis antigen was detected in 10.5% (10/95) and 34.4% (35/102) of pregnant women and control group, respectively (P < 0.001). The isolation rate of N. gonorrhoeae among pregnant women was 0.0% compared to 7.8% (8/102) among the control group (P < 0.01). N. gonorrhoeae were resistant to penicillin (62.5%), tetracycline (50%), ampicillin (25%), amoxycillin–clavulinic acid (25%) and ciprofloxacin (37.5%), while they were susceptible to cefepime, ceftriaxone, ceftazidime, spectinomycin, and cefuroxime.
Conclusion:
Screening of pregnant women for C. trachomatis infection should be included in the antenatal care in this area. The detection rate of both organisms among the control group highlights the importance of preventive strategies. Certain antibiotics previously used in treating gonorrhea are no longer effective.
doi:10.4103/0253-7184.74976
PMCID: PMC3122585  PMID: 21716786
Chlamydia trachomatis; Neisseria gonorrhoeae; sexually transmitted infections
14.  Bile Salts: Natural Detergents for the Prevention of Sexually Transmitted Diseases 
The development of new, safe, topical microbicides for intravaginal use for the prevention of sexually transmitted diseases is imperative. Previous studies have suggested that bile salts may inhibit human immunodeficiency virus infection; however, their activities against other sexually transmitted pathogens have not been reported. To further explore the potential role of bile salts in preventing sexually transmitted diseases, we examined the in vitro activities and cytotoxicities of select bile salts against Chlamydia trachomatis, herpes simplex virus (types 1 and 2), Neisseria gonorrhoeae, and human immunodeficiency virus in comparison to those of nonoxynol-9 and benzalkonium chloride using both primary cells and cell lines derived from the human female genital tract. We found that taurolithocholic acid 3-sulfate and a combination of glycocholic acid and taurolithocholic acid 3-sulfate showed excellent activity against all of the pathogens assayed. Moreover, taurolithocholic acid 3-sulfate alone or in combination was less cytotoxic than nonoxynol-9 and benzalkonium chloride. Thus, taurolithocholic acid 3-sulfate alone or in combination warrants further evaluation as a candidate topical microbicidal agent.
PMCID: PMC89201  PMID: 10103175
15.  The inflammatory cytokine response to Chlamydia trachomatis infection is endotoxin mediated. 
Infection and Immunity  1995;63(8):3125-3130.
Chlamydia trachomatis is a major etiologic agent of sexually transmitted diseases. Although C. trachomatis is a gram-negative pathogen, chlamydial infections are not generally thought of as endotoxin-mediated diseases. A molecular characterization of the acute immune response to chlamydia, especially with regard to the role of its lipopolysaccharide (LPS), remains to be undertaken. We extracted 15 mg of LPS from 5 x 10(12) C. trachomatis elementary bodies (EB) for analysis of structure and biological activity. When methylated lipid A was subjected to high-pressure liquid chromatography followed by mass spectrometry, the majority of the lipid A was found to be pentaacyl. The endotoxin activities of whole C. trachomatis EB and purified LPS were characterized in comparison with whole Salmonella minnesota R595 and with S. minnesota R595 LPS and lipooligosaccharide from Neisseria gonorrhoeae. Both C. trachomatis LPS and whole EB induced the release of tumor necrosis factor alpha from whole blood ex vivo, and C. trachomatis LPS was capable of inducing the translocation of nuclear factor kappa B in a Chinese hamster ovary fibroblast cell line transfected with the LPS receptor CD14. In both assays, however, C. trachomatis was approximately 100-fold less potent than S. minnesota and N. gonorrhoeae. The observation that C. trachomatis is a weak inducer of the inflammatory cytokine response correlates with the clinical observation that, unlike N. gonorrhoeae infection, genital tract infection with C. trachomatis is often asymptomatic. The ability of specific LPS antagonists to completely inhibit the tumor necrosis factor alpha-inducing activity of whole C. trachomatis EB suggests that the inflammatory cytokine response to chlamydia infection may be mediated primarily through LPS. This implies that the role of other surface protein antigens, at least in terms of eliciting the proinflammatory cytokine response, is likely to be minor.
PMCID: PMC173426  PMID: 7542638
16.  Twice-Daily Application of HIV Microbicides Alters the Vaginal Microbiota 
mBio  2012;3(6):e00370-12.
ABSTRACT
Vaginal HIV microbicides offer great promise in preventing HIV transmission, but failures of phase 3 clinical trials, in which microbicide-treated subjects had an increased risk of HIV transmission, raised concerns about endpoints used to evaluate microbicide safety. A possible explanation for the increased transmission risk is that the agents shifted the vaginal bacterial community, resulting in loss of natural protection and enhanced HIV transmission susceptibility. We characterized vaginal microbiota, using pyrosequencing of bar-coded 16S rRNA gene fragments, in samples from 35 healthy, sexually abstinent female volunteer subjects (ages 18 to 50 years) with regular menses in a repeat phase 1 study of twice-daily application over 13.5 days of 1 of 3 gel products: a hydroxyethylcellulose (HEC)-based “universal” placebo (10 subjects), 6% cellulose sulfate (CS; 13 subjects), and 4% nonoxynol-9 (N-9; 12 subjects). We used mixed effects models inferred using Bayesian Markov chain Monte Carlo methods, which showed that treatment with active agents shifted the microbiota toward a community type lacking significant numbers of Lactobacillus spp. and dominated by strict anaerobes. This state of the vaginal microbiota was associated with a low or intermediate Nugent score and was not identical to bacterial vaginosis, an HIV transmission risk factor. The placebo arm contained a higher proportion of communities dominated by Lactobacillus spp., particularly L. crispatus, throughout treatment. The data suggest that molecular evaluation of microbicide effects on vaginal microbiota may be a critical endpoint that should be incorporated in early clinical assessment of microbicide candidates.
IMPORTANCE
Despite large prevention efforts, HIV transmission and acquisition rates remain unacceptably high. In developing countries, transmission mainly occurs through heterosexual intercourse, where women are significantly more vulnerable to infection than men. Vaginal microbicides are considered to be one of the most promising female-controlled products, in that women themselves insert the microbicides into the vagina to prevent HIV transmission during sexual intercourse. The failure of several microbicides in clinical trials has raised questions concerning the low in vivo efficacy of such anti-HIV molecules. This study was designed to gain insights into the failures of two microbicides by testing the hypothesis that the microbicides negatively affect a critical line of defense against HIV, the vaginal microbiota. The results suggest that in the early assessment of candidate microbicides, culture-independent evaluation of their effect on the vaginal microbiota should be considered and may constitute a critical endpoint.
doi:10.1128/mBio.00370-12
PMCID: PMC3529542  PMID: 23249810
17.  Performance of Three Nucleic Acid Amplification Tests for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by Use of Self-Collected Vaginal Swabs Obtained via an Internet-Based Screening Program ▿  
Journal of Clinical Microbiology  2009;47(6):1663-1667.
Use of self-obtained vaginal specimens processed by nucleic acid amplification tests (NAATs) has significantly increased the utilization of nontraditional locations for Chlamydia trachomatis and Neisseria gonorrhoeae screening programs. One important emerging source of such venues includes home-based self-sampling kits available via the Internet. The objective of our study was to evaluate the performance of three commercially available NAATs (Becton-Dickinson ProbeTec SDA, Gen-Probe Aptima Combo2 TMA, and Roche Amplicor PCR) for detection of C. trachomatis and N. gonorrhoeae in vaginal samples obtained via an Internet-based screening program. From July 2004 to August 2005, 500 self-collected vaginal swabs were tested for C. trachomatis and N. gonorrhoeae by using all three NAATs. Another 500 samples were collected between August 2005 and November 2007 and tested by ProbeTec and Combo2; PCR testing was discontinued due to low specificity for N. gonorrhoeae. All tests were conducted according to the manufacturers' procedures; the “gold standard” for an infected C. trachomatis or N. gonorrhoeae patient was defined as ≥2 positive NAAT results. Of the first 500 swabs submitted, 46 were C. trachomatis infected (9.2%) and 5 were N. gonorrhoeae infected (1.0%), and 3 of these were coinfected (0.6%). All C. trachomatis and N. gonorrhoeae Combo2-positive/ProbeTec-negative samples were confirmed as true positives by an alternative NAAT. For C. trachomatis, ProbeTec, Combo2, and PCR had sensitivities of 82.6%, 100%, and 100%, with specificities of 100%, 100%, and 99.3%, respectively. For N. gonorrhoeae, ProbeTec, Combo2, and PCR had sensitivities of 80%, 100%, and 100%, with specificities of 100%, 100%, and 98.8%, respectively. Of the total 1,000 swabs submitted, 92 were C. trachomatis infected (9.2%) and 15 were N. gonorrhoeae infected (1.5%), and 7 of these were coinfected (0.7%). There were no ProbeTec-positive/Combo2-negative samples. For C. trachomatis, ProbeTec and Combo2 had sensitivities of 81.5% and 100%, with specificities of 100% and 100%, respectively. For N. gonorrhoeae, ProbeTec and Combo2 had sensitivities of 80% and 100%, with specificities of 100% and 100%, respectively. Overall, ProbeTec had 17 C. trachomatis false-negative results (1.7%) and 3 N. gonorrhoeae false-negative results (0.3%), while Combo2 had none. Our results were consistent with the sensitivities and specificities stated by the manufacturers. NAATs perform well for detection of chlamydia and gonorrhea with self-obtained vaginal swabs shipped in a dry state to a laboratory. For 1,000 self-collected vaginal swabs tested by NAATs, the sensitivities for C. trachomatis and N. gonorrhoeae for Combo2 were 100% and 100%, while they were 81.5% and 80%, respectively, for ProbeTec. For 500 PCR samples, the C. trachomatis sensitivity was 100% and the N. gonorrhoeae sensitivity was 100%, with specificities of 99.3% and 98.8%, respectively.
doi:10.1128/JCM.02387-08
PMCID: PMC2691063  PMID: 19386838
18.  Gonorrhoea 
Clinical Evidence  2007;2007:1604.
Introduction
In the UK, diagnoses rates for gonorrhoea in 2005 were 196/100,000 for 20-24 year old men, and 133/100,000 for 16-19 year old women. Co-infection with Chlamydia trachomatis is reported in 10-40% of people with gonorrhoea in the USA and UK.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for uncomplicated infections in men and non-pregnant women; and in pregnant women? What are the effects of treatments for disseminated gonococcal infection? What are the effects of dual treatment for gonorrhoea and chlamydia infection? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotic regimens (dual treatment, multiple dose, single dose).
Key Points
Gonorrhoea is caused by infection with Neisseria gonorrhoeae. In men, uncomplicated urethritis is the most common manifestation while in women only about half of cases produce symptoms (such as vaginal discharge and dyspareunia). In the UK, diagnoses rates for gonorrhoea were 196/100 000 for 20-24 year old men and 133/100 000 for 16-19 year old women in 2005.Co-infection with Chlamydia trachomatis is reported in 10-40% of people with gonorrhoea in the USA and UK.
Single dose antibiotic regimens have achieved cure rates of 95% or higher in men and non-pregnant women with urogenital or rectal gonorrhoea. However, resistance to many widely available antibiotics (e.g. penicillins, tetracylines, fluoroquinolones) continues to spread, making it necessary to consider local N gonorrhoeae susceptibility patterns when choosing a treatment regimen. Single dose antibiotics are also effective for curing gonorrhoea in pregnant women.
In people with disseminated gonococcal infection, there is consensus that multidose regimens using injectable cephalosporins or fluoroquinolones (when the infecting organism is known to be susceptible) are the most effective treatments, although evidence supporting this is somewhat sparse.
We did not find any sufficient evidence to judge the best treatment for people with both gonorrhoea and chlamydia, although theory, expert opinion, and clinical experience suggest a combination of antimicrobials active against both N gonorrhoeae and C trachomatis are effective.
PMCID: PMC2943790  PMID: 19454057
19.  Gonorrhoea 
Clinical Evidence  2011;2011:1604.
Introduction
In the UK, diagnosis rates for gonorrhoea in 2008 were 152/100,000 for men aged 20 to 24 years and 135/100,000 for women aged 16 to 19 years. Resistance to one or more antimicrobial agent is reported in more than one quarter of isolates. Co-infection with Chlamydia trachomatis is reported in 10% to 40% of people with gonorrhoea in the US and UK.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for uncomplicated infections in men and non-pregnant women; and in pregnant women? What are the effects of treatments for disseminated gonococcal infection? What are the effects of dual treatment for gonorrhoea and chlamydia infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotic regimens (dual treatment, multiple dose, single dose).
Key Points
Gonorrhoea is caused by infection with Neisseria gonorrhoeae. In men, uncomplicated urethritis is the most common manifestation, while in women less than half of cases produce symptoms (such as vaginal discharge and dyspareunia). Rates of diagnosed gonorrhoea infection in the UK fell by more than 30% between 2002 and 2009.In the UK in 2008, diagnosis rates for gonorrhoea were 152/100,000 for men aged 20 to 24 years, and 135/100,000 for women aged 16 to 19 years.Rates are highest in men aged 20 to 24 years and women aged 16 to 19 years.In the UK, some studies have shown that 28% of isolates are resistant to ciprofloxacin and 8% to penicillin. There is evidence of reduced susceptibility to cephalosporins.Co-infection with Chlamydia trachomatis is reported in 10% to 40% of people with gonorrhoea in the US and UK.
Single-dose antibiotic regimens have achieved cure rates of 95% and higher in men and non-pregnant women with urogenital or rectal gonorrhoea, although we don't know how different single-dose antibiotic regimens compare with each other. Single-dose antibiotics are also effective for curing gonorrhoea in pregnant women.
In people with disseminated gonococcal infection, there is consensus that multiple-dose regimens using cephalosporins or fluoroquinolones (when the infecting organism is known to be susceptible) are the most effective treatments, although evidence supporting this is somewhat sparse.
We found insufficient evidence to judge the best treatment for people with both gonorrhoea and chlamydia, although theory, expert opinion, and clinical experience suggest that a combination of antimicrobials active against both N gonorrhoeae and C trachomatis is effective.
PMCID: PMC3275146  PMID: 21401969
20.  Lower genital tract infections in HIV-seropositive women in India 
Objectives:
The presence of STD facilitates shedding of HIV and increases HIV-1 disease progression, possibly by increasing plasma viremia. Our aim was to study the presence of various associated Sexually transmitted disease/Reproductory tract infections in HIV-seropositive women in India.
Materials and Methods:
The study included 40 HIV-seropositive women attending the antiretroviral therapy (ART) clinic at Lok Nayak Hospital. An informed consent was taken from all subjects. All cases were subjected to detailed gynecological examination and two types of swabs, i.e., a vaginal swab and a cervical swab were taken for STD/RTIs evaluation. The vaginal swabs were used for preparation of wet mount and KOH mount for diagnosis of trichomoniasis and candidiasis; to make a vaginal smear for Gram staining to diagnose bacterial vaginosis (BV) as per Nugent's criteria; for culture of aerobic bacteria and Candida spp. The cervical swab was used for isolation of Neisseria gonorrhoeae by culture and for detection of Chlamydia trachomatis antigen by Chlamydia microplate enzyme immunoassay kit (BIORAD). All data were analyzed using appropriate statistical tests.
Results:
All 40 cases were evaluated for the presence of STD/RTIs associated with HIV infection. The women belonged to the reproductive age group (15-45 years) and majority (40%) of them were para 2. Most of the women (14, 35%) were in World Health Organization (WHO) stage I and maximum number (28, 70%) had their CD4 cell count more than 200 cells/ml. There was no significant correlation between WHO stage of HIV-seropositive women and their CD4 cell count (P=0.092). Out of 40 cases, 15 (37.5%) were on ART with maximum cases (53.3%) in WHO stage III. The duration of ART was more than 6 months in 9 (60%) cases. The most common presenting complaint was vaginal discharge in women with WHO stage II and III and 27.5% women showed vaginitis on per speculum examination. Laboratory tests showed high prevalence of BV (30%), mixed infection (30%), and candidiasis (10%) among HIV-seropositive women (P<0.001 in both). Women with BV were mostly in WHO stage I (38.4%) and stage II (36.3%), while those with mixed infection were mainly in WHO stage III (36.3%) and stage IV (40%).Women with candidiasis were mainly in WHO stage III. C. trachomatis antigen was found only in one subject (prevalence 2.5%). Both WHO stage and CD4 cell count had no significant correlation with presence of BV (P=0.056 and 0.063, respectively) and candidiasis (P=0.492 and 0.530, respectively). Maximum number of patients on ART had mixed infection (53.3%), while most of the patients (36%) not on ART had BV. There was no significant association between duration of ART and the presence of vaginal infections.
Conclusions:
The prevalence of gynecological symptoms and RTIs in HIV-seropositive women is high enough to warrant routine gynecologic evaluation and RTI screening in these patients. However, larger studies and trials are needed to evaluate the effects of ART on these abnormalities as well as to choose the best screening tool in HIV-seropositive women.
doi:10.4103/0253-7184.85414
PMCID: PMC3195170  PMID: 22021972
HIV; lower genital tract infections; women
21.  Screening for cervical Chlamydia trachomatis infections in two Dutch populations. 
Genitourinary Medicine  1990;66(5):361-366.
Endocervical cultures for Chlamydia trachomatis and Neisseria gonorrhoeae were taken from 492 women attending an outpatient clinic for sexually transmitted diseases (group I) and 560 women seeking legal abortion (group II). Possible risk factors for C trachomatis infection were evaluated by multivariate analysis. The prevalence rates for C trachomatis and N gonorrhoeae were 7.3% and 2.5% in group I and 9.4% and 0.4% in group II. From multivariate analysis it was found that age (p less than 0.01), number of sexual partners (p less than 0.01), abnormal vaginal discharge (p less than 0.01), and endocervical mucopus (p = 0.02) were independently associated with chlamydial infection in group I. In the abortion clinic age (p = 0.03) and endocervical mucopus (p = 0.03) were the only significant independent predictors of C trachomatis. In all women vaginal discharge was collected for Gram staining. A significant higher number of polymorphonuclear cells was seen in the smears of C trachomatis positive women (group I: p = 0.04; group II: p = 0.03). In group II there was also a significant association between C trachomatis and Gardnerella type bacterial flora (p = 0.02) and the presence of comma-shaped rods (p = 0.04). Screening for C trachomatis infection may help to decrease the incidence of (post-abortal) pelvic inflammatory disease. Because screening in abortion clinics is not always possible, decreasing the incidence of postabortal pelvic inflammatory disease could be achieved by using prophylactic antibiotics. Selective use of prophylaxis in high risk patients can minimise costs and the incidence of side effects.
PMCID: PMC1194558  PMID: 2245984
22.  Prevalence of Trichomonas vaginalis and Coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae in the United States as Determined by the Aptima Trichomonas vaginalis Nucleic Acid Amplification Assay 
Journal of Clinical Microbiology  2012;50(8):2601-2608.
Our aim was to determine Trichomonas vaginalis prevalence using the Aptima Trichomonas vaginalis assay (ATV; Gen-Probe) and the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae coinfections in U.S. women undergoing screening for C. trachomatis/N. gonorrhoeae. Discarded urogenital samples from 7,593 women (18 to 89 years old) undergoing C. trachomatis/N. gonorrhoeae screening using the Aptima Combo 2 assay (Gen-Probe) in various clinical settings were tested with ATV. Overall, T. vaginalis, C. trachomatis, and N. gonorrhoeae prevalences were 8.7%, 6.7%, and 1.7%, respectively. T. vaginalis was more prevalent than C. trachomatis or N. gonorrhoeae in all age groups except the 18- to 19-year-old group. The highest T. vaginalis prevalence was in women ≥40 years old (>11%), while the highest C. trachomatis prevalence (9.2%) and N. gonorrhoeae prevalence (2.2%) were in women <30 years old. Coinfection prevalences were 1.3% for C. trachomatis/T. vaginalis, 0.61% for C. trachomatis/N. gonorrhoeae and N. gonorrhoeae/T. vaginalis, and 0.24% for C. trachomatis/N. gonorrhoeae/T. vaginalis and highest in women <30 years old. T. vaginalis prevalence differed by race/ethnicity, with the highest prevalence in black women (20.2%). T. vaginalis prevalence ranged from 5.4% in family planning clinics to 22.3% in jails. Multivariate analysis determined that ages of ≥40 years, black race, and patient locations were significantly associated with T. vaginalis infection. T. vaginalis is the most common sexually transmitted infection (STI) in women of >40 years, while C. trachomatis and N. gonorrhoeae prevalence is lowest in that age group. Higher T. vaginalis prevalence in women of >40 years is probably attributed to the reason for testing, i.e., symptomatic status versus routine screening in younger women. Coinfections were relatively low. High T. vaginalis prevalence in all age groups suggests that women screened for C. trachomatis/N. gonorrhoeae, whether asymptomatic or symptomatic, should be screened for T. vaginalis.
doi:10.1128/JCM.00748-12
PMCID: PMC3421522  PMID: 22622447
23.  Isolation of Salmonella Mutants Resistant to the Inhibitory Effect of Salicylidene acylhydrazides on Flagella-Mediated Motility 
PLoS ONE  2013;8(1):e52179.
Salicylidene acylhydrazides identified as inhibitors of virulence-mediating type III secretion systems (T3SSs) potentially target their inner membrane export apparatus. They also lead to inhibition of flagellar T3SS-mediated swimming motility in Salmonella enterica serovar. Typhimurium. We show that INP0404 and INP0405 act by reducing the number of flagella/cell. These molecules still inhibit motility of a Salmonella ΔfliH-fliI-fliJ/flhB(P28T) strain, which lacks three soluble components of the flagellar T3S apparatus, suggesting that they are not the target of this drug family. We implemented a genetic screen to search for the inhibitors' molecular target(s) using motility assays in the ΔfliH-fliI/flhB(P28T) background. Both mutants identified were more motile than the background strain in the absence of the drugs, although HM18 was considerably more so. HM18 was more motile than its parent strain in the presence of both drugs while DI15 was only insensitive to INP0405. HM18 was hypermotile due to hyperflagellation, whereas DI15 was not hyperflagellated. HM18 was also resistant to a growth defect induced by high concentrations of the drugs. Whole-genome resequencing of HM18 indicated two alterations within protein coding regions, including one within atpB, which encodes the inner membrane a-subunit of the FOF1-ATP synthase. Reverse genetics indicated that the alteration in atpB was responsible for all of HM18's phenotypes. Genome sequencing of DI15 uncovered a single A562P mutation within a gene encoding the flagellar inner membrane protein FlhA, the direct role of which in mediating drug insensitivity could not be confirmed. We discuss the implications of these findings in terms of T3SS export apparatus function and drug target identification.
doi:10.1371/journal.pone.0052179
PMCID: PMC3534715  PMID: 23300965
24.  Evaluation of Self-Collected Glans and Rectal Swabs from Men Who Have Sex with Men for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by Use of Nucleic Acid Amplification Tests▿  
Journal of Clinical Microbiology  2009;47(6):1657-1662.
Self-collected glans and rectal swab specimens from men who have sex with men (MSM) may be appropriate, convenient specimens for testing. We evaluated the use of self-collected swabs for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae by a transcription-mediated amplification test (AC2; Aptima Combo 2; Gen-Probe Inc.) and a strand displacement amplification test (SDA; ProbeTec; Becton Dickinson Co.) in MSM seen at the city sexually transmitted disease clinic in San Francisco, CA. For the glans swab specimen, subjects enrolled early in the study rolled a Dacron swab across the meatus three times (method 1). A slightly more invasive procedure was performed later in the study: the subjects inserted the swab 1/4 in. into the urethra, rotated the swab, and then withdrew the swab (method 2). MSM self-collected a rectal swab specimen and also provided first-catch urine (FCU). Additional rectal swab samples were then obtained by the clinician. For the detection of C. trachomatis and N. gonorrhoeae, all swabs were evaluated by AC2 and SDA, FCU was tested by AC2, and the clinician-collected rectal swabs were cultured. A rectal true-positive (TP) result was defined as a culture-positive result for C. trachomatis or N. gonorrhoeae, two or more positive nucleic acid amplification test (NAAT) results, or a single NAAT-positive result confirmed by an alternate amplification method (the Aptima C. trachomatis or N. gonorrhoeae test). A glans TP result was defined as a positive result for FCU, positive results for both glans specimens (one tested by AC2 and one tested by SDA), or a positive result for a single glans specimen confirmed by an alternate amplification method. The prevalence rates of C. trachomatis and N. gonorrhoeae by testing of FCU were 6.8% (60/882 specimens) and 12.2% (108/882 specimens), respectively. Mixed results were obtained with the glans swab: N. gonorrhoeae detection by AC2 and SDA (method 1) had the best performance (sensitivities, >92%) with samples from a population with a higher prevalence of infection, but their performance for the detection of C. trachomatis was poor and varied by collection method (sensitivities, 56 to 68%). The prevalence rates of C. trachomatis and N. gonorrhoeae in the rectum were 7.3% (66/907 specimens) and 9.4% (83/882 specimens), respectively. The sensitivities of the tests with self-collected and clinician-collected rectal swab specimens were comparable (for C. trachomatis, 41% and 44%, respectively, by SDA and 82% and 71%, respectively, by AC2; for N. gonorrhoeae, 77% and 68%, respectively, by SDA and 84% and 78%, respectively, by AC2). AC2 and SDA were far superior to culture for the detection of C. trachomatis and N. gonorrhoeae in the rectum, with both tests detecting at least twice as many infections. While we found self-collected rectal swabs from MSM to be valid specimens for testing, the sensitivities of the tests with glans swab specimens were disappointing except for those from patients with symptomatic N. gonorrhoeae infections. Self-collected glans swab specimens may not be appropriate for the detection of C. trachomatis or for the detection of N. gonorrhoeae in low-risk or asymptomatic patients by AC2 and SDA, and we would not recommend their use on the basis of our results. Further studies are needed.
doi:10.1128/JCM.02269-08
PMCID: PMC2691064  PMID: 19369445
25.  In vitro activity of difloxacin hydrochloride (A-56619), A-56620, and cefixime (CL 284,635; FK 027) against selected genital pathogens. 
Management of sexually transmitted diseases is facilitated by having antimicrobial agents with activity against all of the major genital pathogens. Newer quinolones show promise of being active against Neisseria gonorrhoeae and Chlamydia trachomatis. Two quinolones, difloxacin (A-56619) and A-56620, and an oral cephalosporin, cefixime (CL 284,635; FK 027), were evaluated in vitro. All three were highly active against 400 isolates of N. gonorrhoeae, including penicillinase-producing N. gonorrhoeae, N. gonorrhoeae with chromosomally mediated resistance, and isolates with penicillin MICs of less than 1 microgram/ml. Susceptibilities to one antimicrobial agent were usually strongly correlated with susceptibilities to the other antimicrobial agents evaluated, but isolates with increasing resistance to beta-lactams were least likely to show increasing resistance to quinolones. Difloxacin and, to a lesser extent, A-56620 were active against all 10 strains of C. trachomatis, and both had moderate activity against over 200 strains of Gardnerella vaginalis. Based on in vitro activity, difloxacin and A-56620 merit in vivo assessment for management of both C. trachomatis and N. gonorrhoeae infections, and cefixime shows considerable promise for treatment of N. gonorrhoeae infections.
PMCID: PMC176486  PMID: 3098163

Results 1-25 (437254)