Search results for: chlamydia trachomatis

Authors: Siwimol Phoomniyom, Pathom Karaipoom, Rossaphorn Kittyaowaman

Abstract:

Background: C. trachomatis is the most common bacterial sexually transmitted infections. Although infection with C. trachomatis can be treated with antibiotic, it is frequently asymptomatic, especially in extragenital sites. Hence, if screening tests are not performed, undetected and untreated is a crucial problem for C. trachomatis infection, especially in Thailand, which is less well studied. We sought to assess the prevalence of C. trachomatis infection in multiple anatomical sites among patients attending Bangrak STIs Center. Methods: We examined laboratory results of all patients at baseline visit from 3 January 2018 to 27 December 2019. These results were tested by a validated in-house real time PCR specify for the cryptic plasmid gene of C. trachomatis. The prevalence of C. trachomatis was analyzed by anatomical sites, sexes, and ages. Urogenital samples were obtained from urethral swab of men and cervical swab of women. The median ages of the patients were 32 years (range 13-89 years). Chi-square test by IBM SPSS statistic version 20 was used to assess difference in the distribution of variables between groups. Results: Among 3,789 patients, the prevalence for C. trachomatis infection was the highest in rectal (16.1%), followed by urogenital (11.2%) and pharyngeal (3.5%) sites. Rectal and urogenital infection in men was higher than in women, with the highest prevalence of 16.6% in rectal site. Both rectal and urogenital sites also showed statistically significant differences between sexes (P<0.001). Meanwhile, pharyngeal C. trachomatis infection rate was higher in women than men. Interestingly, the chlamydia prevalence was the highest in age 13-19 years of all three sites (18.5%, urogenital; 17.7%, rectal; 6.5%, pharyngeal), with statistically significant difference between age groups (P<0.001). Total of 45 C. trachomatis infections, 20.0%, 51.1%, and 6.7% were isolated from urogenital, rectal, and pharyngeal sites. In total, 75.6%, 26.7%, and 80.0% of chlamydia infections would have been missed, if only urogenital, rectal, or pharyngeal screening was performed. Conclusions: The highest source of C. trachomatis infection was the rectal site. While, the highest prevalence in men was at rectal site, that in women was at urogenital site. The highest chlamydia prevalence was found in adolescent age group, indicating that the pediatric population was a high-risk group. This finding also elucidated that a high proportion of C. trachomatis infection would be missed, if only single anatomical site screening was performed, especially in extragenital sites. Hence, extragenital screening is also required for the extensive C. trachomatis detection.

Keywords: chlamydia trachomatis, anatomical sites, sexes, ages

Procedia PDF Downloads 69

Authors: Trenton Hubbard, Kenneth Soyemi, Emily Siffermann

Abstract:

Introduction: According to the American Academy of Pediatrics (AAP) there are different weight-based recommendations for the treatment of Chlamydia trachomatis (CT) in patients who are being evaluated for sexual assault. Current AAP Red Book guidelines recommend that uncomplicated C. trachomatis anogenital infection in prepubertal patients weighing less than =<45 kg be treated with oral erythromycin 50 mg/kg/day QID for 14 days with no alternative therapies, and for patients whose weight => 45 kg are Azithromycin 1 gm PO once. Our study objective was to determine the efficacy of single-dose Azithromycin therapy for the treatment of Chlamydia trachomatis in patients weighing less than 50 kg who were evaluated for child sexual abuse in an urban setting. Methods: We conducted a retrospective chart review of historical medical records (paper and electronic) patients weighing less than 50 kg who were evaluated for child sexual abuse and subsequently treated for C. trachomatis infection with Azithromycin (20 mg/kg PO once up to a maximum 1 gm) and received a Test of Cure (TOC) from 2006-2016. Qualitative variables were expressed as percentages. Quantitative variables were expressed as mean values (+/- standard deviation [SD]) if they followed a normal distribution or as median values (interquartile range[IQR]) if they did not. Wilcoxson two-sample test was used to compare means of Azithromycin Dose, mg/kg, and TOC timing between treatment responders and non-responders. Results: We reviewed records of 34 patients, average age (SD) was 5.4 (2.0) years, 33 (97%) were treated for CT and 1(3%) for both GC and CT. 25 (74%) were females. Urine PCR was the most commonly used test at evaluation and as TOC with 13 (38%) patients completing both tests. The average (SD) dose of Azithromycin at treatment was 470 (136) mg and average (SD) mg/kg dose of 20 (1.9) mg/kg for all patients. Median (IQR) timing for TOC testing was 19 (14-26) days. Of the 33 with complete data 25 (74%) had a negative TOC. When compared with treatment non-responders (TOC failures), treatment responders received higher doses (average dose (SD) received 495 (139) vs 401(110), P 0.06)); similar average (SD) weight base dosing received (20.8(2.0) vs 19.7 (1.5), P 0.15)), and earlier average (SD)TOC test timing (18.8 (5.6) vs 32 (28.6) P 0.02)). Conclusion: Azithromycin dosing appears to be efficacious in the treatment of CT post sexual assault as majority of patients responded. Although treatment responders and non-responders received similar weight based doses, there is need for additional studies to understand variances and predictors of response.

Keywords: child sexual abuse, chlmaydia trachmotis infection, single-dose azithromycin, weight less than or equal to 45 kilograms

Procedia PDF Downloads 292

Authors: Monika Szymańska-Czerwińsk, Kinga Zaręba-Marchewka, Krzysztof Niemczuk

Abstract:

Chlamydiaceae are Gram-negative bacteria distributed worldwide in animals and humans. One of them is Chlamydia gallinacea recently discovered. Available data show that C. gallinacea is dominant chlamydial agent found in poultry in European and Asian countries. The aim of the studies was screening of poultry flocks in order to evaluate frequency of C. gallinacea shedding and genetic diversity. Sampling was conducted in different regions of Poland in 2019-2020. Overall, 1466 cloacal/oral swabs were collected in duplicate from 146 apparently healthy poultry flocks including chickens, turkeys, ducks, geese and quails. Dry swabs were used for DNA extraction. DNA extracts were screened using a Chlamydiaceae 23S rRNA real-time PCR assay. To identify Chlamydia species, specific real-time PCR assays were performed. Furthermore, selected samples were used for sequencing based on ompA gene fragments and variable domains (VD1-2, VD3-4). In total, 10.3% of the tested flocks were Chlamydiaceae-positive (15/146 farms). The presence of Chlamydiaceae was confirmed mainly in chickens (13/92 farms) but also in turkey (1/19 farms) and goose (1/26 farms) flocks. Eleven flocks were identified as C. gallinacea-positive while four flocks remained unclassified. Phylogenetic analysis revealed at least 16 genetic variants of C. gallinacea. Research showed that Chlamydiaceae occur in a poultry flock in Poland. The strains of C. gallinacea as dominant species show genetic variability.

Keywords: C. gallinacea, emerging agent, poultry, real-time PCR

Procedia PDF Downloads 103

Authors: Tri Nguyen

Abstract:

Background: Female sex workers (FSWs) are at heightened risk of sexually transmitted infections (STIs) and HIV. The purpose of the research is to study FSWs socio-demographic and behavioral characteristics and their HIV/STIs prevalence in Ba Ria – Vung Tau, Vietnam. Methods: A cross-sectional survey of 420 direct and indirect FSWs between January and May, 2014 from 2 cities and 6 districts in Ba Ria – Vung Tau were collected using sampling methods. FSWs were interviewed using the structured questionnaire and biological samples were tested for syphilis, gonorrhoea, chlamydia and HIV in the study. A database was constructed and entered using Epidata 3.1 software and analyzed using the SPSS 20.0 statistical package. Results: A total of 420 FSWs participated in the survey, with a median age of 27 years within a range of 18 – 43 years. Education levels were low with 33.1% only completing all seven major indicators. The median age of first sexual intercourse of the FSWs was 18 years. Most (88.8%) of the FSWs had oral sex. A high proportion (82.4 %) of the FSWs had consumed alcohol. Among them, 51.2% of the FSWs have had sex after drunk. Of the 177 FSWs have reported that they have had sex after drunk, almost half of direct FSWs have had unprotected sex. Among the 420 FSWs who participated in the survey, 2.6 % (11/420) were found to be HIV positive. There was a difference in HIV prevalence among direct and indirect FSWs (4.8 % and 1.2%, p= 0,022). Nearly 7 percent of the FSWs were infected with Syphilis. Similarly, the percentage (7.9 %) of the FSWs was found with Gonorrhoea and a doubly higher percentage (16.4%) of them was suffering from Chlamydia. On the aggregate, the percentage of FSWs with any one of the STIs (Gonorrhoea or Chlamydia) was highest 21.4 %. Conclusions: FSWs in Ba Ria – Vung Tau, Vietnam are highly vulnerable to STIs and need to enhance the existing STIs treatment and intervention programs in order to reduce the risk of HIV infections. HIV/STIs health education and a 100% condom use program should be implemented, and sex industry should be regulated by law.

Keywords: sex workers, female sex workers, HIV, STIs

Procedia PDF Downloads 255

Authors: Anthony J. Kondracki, Bonzo Reddick, Jennifer L. Barkin

Abstract:

Background: Many pregnancies in the United States are affected each year with the most common sexually transmitted infections (STIs), including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Treponema pallidum (TP, syphilis), and the rate of congenital syphilis has reached a 20-year high. We sought to estimate the prevalence of CT, NG, and TP in pregnancy and the risk of preterm birth (PTB) (<37 weeks gestation) and low birthweight (LBW) (<2500g) deliveries according to utilization of prenatal care (PNC) during the COVID-19 pandemic. Methods: This study was based on the 2020 National Center for Health Statistics (NCHS) Natality File restricted to singleton births (N=3,512,858). We estimated the prevalence of CT, NG, TP, PTBand LBW across timing and the number of prenatal care (PNC) visits attended. In multivariable logistic regression models, adjusted odds ratios of PTB and LBW were assessed according to STIs and PNC status. E-values, based on effect size estimates and the lower bound of the 95% confidence intervals (CIs) of the association, examined the potential impact of unmeasured confounding. Results: CT (1.8%) was most prevalent in pregnancy, followed by NG (0.3%) and TP (0.1%). The strongest predictors of PTB and LBW were maternal NG (12.2% and 12.1%, respectively), late initiation/no PNC (8.5% and 7.6%, respectively), and ≤10 prenatal visits (13.1% and 10.3%, respectively). The odds of PTB and LBW were 2.5- to 3-fold greater for each STI in women who received ≤10 compared to >10 prenatal visits. E-values demonstrated the minimum strength of potential unmeasured confounding necessary to explain away observed associations. Conclusions: Timely initiation and receipt of recommended number of prenatal visits benefits screening and treatment of all women for STIs, including NG to substantially reduce infant morbidity and mortality related to PTB and LBW among infants born during the COVID-19 pandemic.

Keywords: COVID-19 pandemic, sexually transmitted infections, preterm birth, low birthweight, prenatal care

Procedia PDF Downloads 152

Authors: Anthony J. Kondracki, Bonzo I. Reddick, Jennifer L. Barkin

Abstract:

We sought to examine the association of maternal Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and treponema pallidum (TP) (syphilis) infections with preterm birth (PTB) (<37 weeks gestation), low birth weight (LBW) (<2500 grams) and prenatal care (PNC) attendance. This cross-sectional study was based on data drawn from the 2020 United States National Center for Health Statistics (NCHS) Natality File. We estimated the prevalence of all births, early/late PTBs, moderately/very LBW, and the distribution of sexually transmitted infections (STIs) according to maternal characteristics in the sample. In multivariable logistic regression models, we examined adjusted odds ratios (aORs) and their corresponding 95% confidence intervals (CIs) of PTB and LBW subcategories in the association with maternal/infant characteristics, PNC status, and maternal CT, NG, and TP infections. In separate logistic regression models, we assessed the risk of these newborn outcomes stratified by PNC status. Adjustments were made for race/ethnicity, age, education, marital status, health insurance, liveborn parity, previous preterm birth, gestational hypertension, gestational diabetes, PNC status, smoking, and infant sex. Additionally, in a sensitivity analysis, we assessed the association with early, full, and late term births and the potential impact of unmeasured confounding using the E-value. CT (1.8%) was most prevalent STI in pregnancy, followed by NG (0.3%), and TP (0.1%). Non-Hispanic Black women, 20-24 years old, with a high school education, and on Medicaid had the highest rate of STIs. Around 96.6% of women reported receiving PNC and about 60.0% initiated PNC early in pregnancy. PTB and LBW were strongly associated with NG infection (12.2% and 12.1%, respectively) and late initiation/no PNC (8.5% and 7.6%, respectively), and ≤10 prenatal visits received (13.1% and 10.3%, respectively). The odds of PTB and LBW were 2.5- to 3-foldhigher for each STI among women who received ≤10 prenatal visits than >10 visits. Adequate prenatal care utilization and timely screening and treatment of maternal STIs can substantially reduce the burden of adverse newborn outcomes.

Keywords: low birthweight, prenatal care, preterm birth, sexually transmitted infections

Procedia PDF Downloads 172

Authors: L. Ereku, R. E. Mackay, A. Naveenathayalan, K. Ajayi, W. Balachandran

Abstract:

Over the past decade the increase of sexually transmitted infections (STIs) especially in the developing world due to high cost and lack of sufficient medical testing have given rise to the need for a rapid, low cost point of care medical diagnostic that is disposable and most significantly reproduces equivocal results achieved within centralised laboratories. This paper present the development of a disposable PDMS microfluidic cartridge incorporating blisters filled with reagents required for isothermal DNA amplification in clinical diagnostics and point-of-care testing. In view of circumventing the necessity for external complex microfluidic pumps, designing on-chip pressurised fluid reservoirs is embraced using finger actuation and blister storage. The fabrication of the blisters takes into consideration three proponents that include: material characteristics, fluid volume and structural design. Silicone rubber is the chosen material due to its good chemical stability, considerable tear resistance and moderate tension/compression strength. The case of fluid capacity and structural form go hand in hand as the reagent need for the experimental analysis determines the volume size of the blisters, whereas the structural form has to be designed to provide low compression stress when deformed for fluid expulsion. Furthermore, the top and bottom section of the blisters are embedded with miniature polar opposite magnets at a defined parallel distance. These magnets are needed to lock or restrain the blisters when fully compressed so as to prevent unneeded backflow as a result of elasticity. The integrated chip is bonded onto a large microscope glass slide (50mm x 75mm). Each part is manufactured using a 3D printed mould designed using Solidworks software. Die-casting is employed, using 3D printed moulds, to form the deformable blisters by forcing a proprietary liquid silicone rubber through the positive mould cavity. The set silicone rubber is removed from the cast and prefilled with liquid reagent and then sealed with a thin (0.3mm) burstable layer of recast silicone rubber. The main microfluidic cartridge is fabricated using classical soft lithographic techniques. The cartridge incorporates microchannel circuitry, mixing chamber, inlet port, outlet port, reaction chamber and waste chamber. Polydimethylsiloxane (PDMS, QSil 216) is mixed and degassed using a centrifuge (ratio 10:1) is then poured after the prefilled blisters are correctly positioned on the negative mould. Heat treatment of about 50C to 60C in the oven for about 3hours is needed to achieve curing. The latter chip production stage involves bonding the cured PDMS to the glass slide. A plasma coroner treater device BD20-AC (Electro-Technic Products Inc., US) is used to activate the PDMS and glass slide before they are both joined and adequately compressed together, then left in the oven over the night to ensure bonding. There are two blisters in total needed for experimentation; the first will be used as a wash buffer to remove any remaining cell debris and unbound DNA while the second will contain 100uL amplification reagents. This paper will present results of chemical cell lysis, extraction using a biopolymer paper membrane and isothermal amplification on a low-cost platform using the finger actuated blisters for reagent storage. The platform has been shown to detect 1x105 copies of Chlamydia trachomatis using Recombinase Polymerase Amplification (RPA).

Keywords: finger actuation, point of care, reagent storage, silicone blisters

Procedia PDF Downloads 368

Authors: Rudraksh Kesharwani, Ritika Agarkar

Abstract:

Sexually transmitted diseases are a major public health concern affecting both the mortality and the morbidity of a population. It is among the most serious causes of the diseases affecting the quality of life of a individual leading to a significant decrease in their health. In India, STIs have been a significant public health concern due to various reasons, including a large population, limited access to healthcare in certain areas, stigma around discussing sexual health, and insufficient sex education. Some common STIs in India include HIV/AIDS, syphilis, gonorrhea, chlamydia, and herpes. This research report aims to determine the percentage of people infected with sexually transmitted infections (STI) worrying about it’s impact on their day to day activity, specifically focusing on it’s impact on the mentaland sexual health of the patient infected along with his/her partner.

Keywords: sexual health, mental health, sexually transmitted disease, sexual taboos

Procedia PDF Downloads 14

Authors: Shanna Su, Kathleen Vincent

Abstract:

Introduction: A non-hormonal prescription vaginal pH modulator (VPM) gel (Phexxi®), with active ingredients lactic acid, citric acid, and potassium bitartrate, has recently been approved for the prevention of pregnancy in the United States. The objective of this review is to compile the evidence available from published preclinical and clinical trials to support its use. Areas covered: PubMed was searched for published literature on VPM gel. Two Phase III trials were found on the clinicaltrials.gov database. The results demonstrated that VPM gel is safe, with minimal side effects, and effective (cumulative 6-7 cycle pregnancy rate of 4.1-13.65%, (Pearl Index 27.5) as a contraceptive. Microbicidal effects suggest the potential for the prevention of sexually transmitted infections (STIs); currently, a Phase III clinical trial is being conducted to evaluate the prevention of chlamydia and gonorrhea. Expert opinion: Non-hormonal reversible contraceptive options have been limited to the highly effective copper-releasing intrauterine device that requires insertion by a trained clinician and less effective coitally-associated barrier and spermicide options which are typically available over-the-counter. Spermicides, which improve the efficacy of barrier devices, may increase the risk of Human Immunodeficiency Virus (HIV)/STIs. VPM gel provides a new safe, effective non-hormonal contraceptive option with the potential for prevention of STIs.

Keywords: citric acid, lactic acid, non-hormonal contraception, potassium bitartrate, topical vaginal contraceptive, vaginal pH modulator gel

Procedia PDF Downloads 99

Authors: Swati Gautam, Amita Jain, Shyampyari Jaiswar

Abstract:

Objective: To elucidate the role of (ApaI&TaqI) VDR gene polymorphism in the pathogenesis of female genital tuberculosis (FGTB) cases. Background: Female genital TB represents about 15-20% of total extra-pulmonary TB (EPTB). Female subjects with vitamin D deficiency have been shown to be at higher risk of pulmonary TB as well as FGTB. In same context few functional polymorphism in vitamin D receptor (VDR) gene has been considered as an important genetic risk factor that modulate the development of FGTB. Therefore we aimed, to elucidate the role of (ApaI&TaqI) VDR gene polymorphism in the pathogenesis of FGTB. Study design: Case-Control study. Sample size: Cases (60) and Controls (60). Study site: Department of Obstetrics & Gynecology & Department of Microbiology, K.G.M.U. Lucknow, (UP). Inclusion criteria: Cases: Women with age group 20-35 years, premenstrual endometrial aspiration collected and included in the study, those were positive with acid-fast bacilli (AFB)/ TB-PCR/ LJ culture/ liquid culture. Controls: Women with age group 20-35 years having no history of ATT and all test negative for TB recruited as control. Exclusion criteria: -Women with endometriosis, polycystic ovaries (PCOD), positive on Chlamydia & gonorrhea, already on anti-tubercular therapy (ATT) excluded. Materials and Methods: Blood samples were collected in EDTA tubes from cases and controls stored at -20ºC. Genomic DNA extraction was carried out by salting-out method. Genotyping of VDR gene (ApaI&TaqI) polymorphism was performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 2% agarose gel. Statistical analysis was done by SPSS16.3 software & computing odds ratio (OR) with 95% CI. Results: Increased risk of female genital tuberculosis was observed in AA genotype (OR =1.1419-6.212 95% CI, P*<0.036) and A allele (OR =1.255-3.518, 95% CI, P* < 0.006) in FGTB as compared to controls. Moreover A allele was found more frequent in FGTB patients. No significant difference was observed in TaqI gene polymorphism of VDR gene. Conclusion: The ApaI polymorphism is significantly associated with etiology of FGTB and plays an important role as a genetic risk factor in FGTB women.

Keywords: ARMS, ATT, EPTB, FGTB, VDR

Procedia PDF Downloads 285

Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

Abstract:

Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

Procedia PDF Downloads 305

Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

Abstract:

According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

Procedia PDF Downloads 344