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Gbenafa-Agossa, Clémence. "Prévalence et facteurs de risque des infections génitales à Neisseria gonorrhoeae et Chlamydia trachomatis chez les travailleuses de sexe au Bénin en 2003-2004 et évaluation d'un test rapide dans le dépistage de la gonococcie génitale." Master's thesis, Université Laval, 2006. http://hdl.handle.net/20.500.11794/18455.
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Berglund, Torsten. "Recent trends in the epidemiology of gonorrhoea in Sweden : the role of importation and core groups /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-692-1/.
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ROCK, JOHN PATRICK. "MOLECULAR BIOLOGY OF GONOCOCCAL DEATH FOLLOWING EXPOSURE TO THE GRANULE EXTRACTS OF HUMAN NEUTROPHILS (NEISSERIA GONORRHOEAE, PEPTIDOGLYCAN, MEMBRANE DAMAGE)." Diss., The University of Arizona, 1986. http://hdl.handle.net/10150/183844.
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Gonococci that have been phagocytized by human neutrophils are killed very effectively. While much research has focused on defining the microbicidal mechanisms of the neutrophil arsenal, substantially less is known regarding why phagocytized bacteria die. Gonococci were examined, at the molecular level, following exposure to human neutrophil granule extracts (GE) in an effort to discover the "lethal lesion", that injury to the bacterial cell which results in its death. The cytoplasm-based metabolism of GE-treated gonococci continues to function normally for at least 30 minutes, although these same cells have lost the ability to divide and are reproductively dead. GE-treated gonococci were found to utilize less oxygen than control cells, indicative of damage to the cytoplasmic membrane. Visual examination of GE-treated gonococci by light microscopy revealed that the cells undergo very minimal division once exposed to GE. GE-treated gonococci visualized by transmission electron microscopy had outer membranes which suffered time-related disorganization and disruption; the effects began immediately upon contact with GE. GE-treatment was also observed to cause aberrant structure and orientation of forming bacterial septa. Investigation of gonococcal peptidoglycan, the structural component of the bacterial membrane, yielded interesting results when the effects of GE were scrutinized. GE caused subnormal incorporation of peptidoglycan precursors, and also induced a twofold higher rate of release of peptidoglycan turnover fragments than was seen from control cells. After analysis of peptidoglycan fragments released into culture supernatants by thin-layer chromatography and high-pressure liquid chromatography, it was found that the small amount of high-molecular-weight fragments exhausted by control cells was not present with treated cells. Investigation of the cell-associated peptidoglycan, by the above methods, after exposure to GE revealed differences in the digestion products. There was a distinct reduction in the amount of penicillin bound by the penicillin-binding proteins of GE-treated cells. There was, however, no observed change in the electrophoretic mobility between the PBPs of control and treated cells.
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McMillan, Noto Jennifer. "Analysis of the mechanism of transferrin-iron acquisition by Neisseria gonorrhoeae." Online version unavailable until 9/16/2013, 2008. http://hdl.handle.net/10156/2294.
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Hernandez, Diana Raquel. "Regulation of Expression of a Neisseria Gonorrhoeae tRNA-Modification Enzyme (Gcp)." Diss., The University of Arizona, 2012. http://hdl.handle.net/10150/242381.
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Neisseria gonorrhoeae (Ng) encounters different microenvironments during its life-cycle. Some of these niches have different concentrations of oxygen, which influences the rate of Ng growth; as well as iron, an element essential for Ng survival. Differential expression of several proteins allows the bacteria to adapt to the diverse conditions it comes encounters. One protein affected by environmental changes during Ng growth is Gcp, a tRNA-modification enzyme essential for protein synthesis. To study the regulation of expression of Gcp, we first analyzed the sequence of its ORF, gcp. Orthologs of this gene are found in all kingdoms of life. In silico analysis shows that among Neisseria species, gcp ranges in homology from 76% to 99%, at the nucleotide level. Reverse transcription PCR indicates that gcp is expressed as part of an operon, together with three cytochrome-associated genes cyc4, resB and resC. Rapid amplification of complementary DNA ends determined the start of transcription of cyc4 (and possibly of the cyc4-gcp operon) at 95 nucleotides from the gene start codon. Transcriptional fusions determined that the promoter region upstream of cyc4 is the strongest promoter in the operon. However, the region directly upstream of gcp also has low level of promoter activity, suggesting that the gene may be expressed from two different promoters. Semi-quantitative determination of the concentration of gcp mRNA indicates that the transcription of the gene is significantly repressed when Ng is grown under low iron or low oxygen conditions. Analysis of an fnr mutant, grown under the same conditions as its parental wild type, indicates that the FNR transcriptional regulator is involved in the repression of gcp in low iron or low oxygen conditions. Contrary to expectation, the cyc4 promoter is upregulated when Ng is grown under low oxygen or low iron conditions. However, these results cannot be compared to the original promoter strength. Determination of which was performed on bacteria grown in liquid medium. Coregulation of gcp with cytochrome genes can guarantee low levels of protein synthesis when Ng encounters adverse microenvironments and needs its energy redirected to the expression of genes that would allow it to survive.
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Perry, Elizabeth Holly. "Association of ABO, Lewis and Secretor phenotypes and genotypes with Neisseria gonorrhoeae thesis submitted in (partial) fulfilment of the Master of Applied Science, Auckland University of Technology, November 2003." Full thesis. Abstract, 2003. http://puka2.aut.ac.nz/ait/theses/PerryE.pdf.
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DeRocco, Amanda Jean. "Molecular Analysis of Transferrin Binding Protein B in Neisseria Gonorrhoeae." VCU Scholars Compass, 2007. http://scholarscompass.vcu.edu/etd_retro/52.
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The transferrin iron acquisition system of Neisseria consists of two dissimilar proteins, transferrin binding protein A and B (TbpA and TbpB). TbpA and TbpB both specifically and independently bind human transferrin (Tf). TbpA is a TonB-dependent transporter, expression of which is necessary for Tf iron acquisition. In contrast, the lipoprotein TbpB is not necessary for iron internalization; however it makes this process more efficient. The role of TbpB in the transferrin iron acquisition system has not been completely elucidated. It has been suggested that TbpB is entirely surface exposed and tethered to the outer membrane by its lipid moiety. We inserted the hemagluttinin antigen (HA) epitope into TbpB in an effort to examine surface accessible and functional domains of the lipoprotein. We determined that TbpB was entirely surface exposed from just beyond the mature N-terminus. It was previously reported that the N- and C-terminus of TbpB independently bind Tf. HA epitope analysis defined both the N-terminal and C-terminal binding domains. TbpB was previously reported to play an important role in the release of Tf from the receptor. We established that TbpB exhibited a biphasic dissociation pattern; a C-terminal rapid release followed by a slower N-terminal release. These results suggested that the C-terminus plays a role in ligand turnover of the wild-type receptor. Little is known about the transport of TbpB to the outer membrane. In an attempt to identify the signals/mechanisms required for TbpB localization, the signal sequence of the protein was altered. In the absence of lipid modification, TbpB remained associated with the cell, localized to the periplasm. We also noted that internal cysteine residues were not critical for TbpB localization. Our results suggested that TbpB was transported by a lipoprotein-specific mechanism. Additionally, we demonstrated the major outer membrane secretin, PilQ, was not necessary for proper localization of TbpB. The mechanism responsible for this process remains elusive. This body of work represents the first comprehensive study of TbpB topology and function, utilizing the lipoprotein expressed in its native membrane. These results may translate to other, similar lipoprotein receptors of the pathogenic Neisseria, helping to shed light on these poorly understood proteins.
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Pickel, Donnie. "Investigating Complement Regulator Involvement in Innate Immune Evasion by Neisseria gonorrhoeae." Ohio University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1628181973757983.
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Wood, Megan Lindsay Falsetta. "Coping with stress: anaerobic respiratory and oxidative stress tolerance mechanisms are critical for Neisseria gonorrhoeae biofilm formation." Diss., University of Iowa, 2009. https://ir.uiowa.edu/etd/450.
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Many illnesses and infections are exacerbated and/or caused by biofilms. Neisseria gonorrhoeae, the etiologic agent of gonorrhea, is frequently asymptomatic in women, which can lead to persistent infection. Persistent infection can result in pelvic inflammatory disease, tubo-ovarian abscesses, infertility, and ectopic pregnancy. N. gonorrhoeae has been shown to form biofilms over glass, primary and immortalized cervical cells, and during natural cervical infection. Asymptomatic infection occurs in only 1% of infected males, and the infection site is subject to periodic rapid fluid flow, which may limit biofilm formation. Thus, biofilm formation may specifically play an important role in the infection of women and could contribute to the infrequent occurrence of symptoms.
Prior to work presented in this dissertation, little was known about biofilm formation by N. gonorrhoeae. Therefore, we elected to compare the transcriptional profiles of biofilms to their planktonic counterparts, to identify genetic pathways involved in biofilm formation and maintenance. We found that 3.8% of the genome was differentially regulated, and that genes involved in anaerobic metabolism and oxidative stress tolerance were up-regulated in biofilm, while genes involved in aerobic metabolism were down-regulated. We determined that expression of aniA , ccp, and norB is required for robust biofilm formation over glass and human cervical cells, and anaerobic respiration occurs in the substratum of gonococcal biofilms. Disruption of the norB gene resulted in severe attenuation of biofilm formation. We determined that the accumulation of nitric oxide (NO) contributes to the phenotype of a norB mutant and can retard biofilm formation when present at sublethal concentrations. However, higher concentrations of NO can enhance biofilm formation in the absence of nitrite. NO enhances biofilm formation in an aniA mutant, but cannot completely restore biofilm formation, suggesting that NO can support anaerobic growth, although nitrite is preferred. We determined that the majority of the genes involved in gonococcal oxidative stress tolerance are required for normal biofilm formation, as mutations in the following genes resulted in biofilm attenuation over cervical cells and/or glass: oxyR, gor, prx, mntABC, trxB, and estD. Overall, biofilm formation may represent an adaptation for coping with the stresses present in the female genitourinary tract.
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Bergman, Peter. "Antimicrobial peptides and pathogenic Neisseria : experimental studies in mouse, man and rat /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-428-7/.
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Chakraborti, Srinjoy. "Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence Factor." eScholarship@UMMS, 2005. http://escholarship.umassmed.edu/gsbs_diss/905.
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Neisseria gonorrhoeae (Ng) which causes gonorrhea has become multidrug-resistant, necessitating the development of novel therapeutics and vaccines. mAb 2C7 which targets an epitope within an important virulence factor, the lipooligosaccharide (LOS), is a candidate therapeutic mAb. Ninety-four percent of clinical isolates express the 2C7-epitope which is also a vaccine target.
Ng expresses multiple LOS(s) due to phase-variation (pv) of LOS glycosyltransferase (lgt) genes. mAb 2C7 reactivity requires a lactose extension from the LOS core Heptose (Hep) II (i.e. lgtG ‘ON’ [G+]). Pv results in HepI with: two (2-), three (3-), four (4-), or five (5-) hexoses (Hex). How HepI glycans impact Ng infectivity and mAb 2C7 function are unknown and form the bases of this dissertation.
Using isogenic mutants, I demonstrate that HepI LOS glycans modulate mAb 2C7 binding. mAb 2C7 causes complement (C’)-dependent bacteriolysis of three (2-Hex/G+, 4-Hex/G+, and 5-Hex/G+) of the HepI mutants in vitro. The 3-Hex/G+ mutant (resistant to C’-dependent bacteriolysis) is killed by neutrophils in the presence of mAb and C’. In mice, 2- and 3-Hex/G+ infections are significantly shorter than 4- and 5-Hex/G+ infections. A chimeric mAb 2C7 that hyperactivates C’, attenuates only 4- and 5-Hex/G+ infections.
This study enhances understanding of the role of HepI LOS pv in gonococcal infections and shows that longer HepI glycans are necessary for prolonged infections in vivo. This is the first study that predicts in vitro efficacy of mAb 2C7 against all four targetable HepI glycans thereby strengthening the rationale for development of 2C7-epitope based vaccines and therapeutics.
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Chakraborti, Srinjoy. "Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence Factor." eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/905.
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Neisseria gonorrhoeae (Ng) which causes gonorrhea has become multidrug-resistant, necessitating the development of novel therapeutics and vaccines. mAb 2C7 which targets an epitope within an important virulence factor, the lipooligosaccharide (LOS), is a candidate therapeutic mAb. Ninety-four percent of clinical isolates express the 2C7-epitope which is also a vaccine target.
Ng expresses multiple LOS(s) due to phase-variation (pv) of LOS glycosyltransferase (lgt) genes. mAb 2C7 reactivity requires a lactose extension from the LOS core Heptose (Hep) II (i.e. lgtG ‘ON’ [G+]). Pv results in HepI with: two (2-), three (3-), four (4-), or five (5-) hexoses (Hex). How HepI glycans impact Ng infectivity and mAb 2C7 function are unknown and form the bases of this dissertation.
Using isogenic mutants, I demonstrate that HepI LOS glycans modulate mAb 2C7 binding. mAb 2C7 causes complement (C’)-dependent bacteriolysis of three (2-Hex/G+, 4-Hex/G+, and 5-Hex/G+) of the HepI mutants in vitro. The 3-Hex/G+ mutant (resistant to C’-dependent bacteriolysis) is killed by neutrophils in the presence of mAb and C’. In mice, 2- and 3-Hex/G+ infections are significantly shorter than 4- and 5-Hex/G+ infections. A chimeric mAb 2C7 that hyperactivates C’, attenuates only 4- and 5-Hex/G+ infections.
This study enhances understanding of the role of HepI LOS pv in gonococcal infections and shows that longer HepI glycans are necessary for prolonged infections in vivo. This is the first study that predicts in vitro efficacy of mAb 2C7 against all four targetable HepI glycans thereby strengthening the rationale for development of 2C7-epitope based vaccines and therapeutics.
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Strange, Heather Ruth. "Mechanism of Iron Transport Employed by Neisseria Gonorrhoeae: Contribution of Ferric Binding Protein A." VCU Scholars Compass, 2007. http://scholarscompass.vcu.edu/etd_retro/80.
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FbpA is the periplasmic binding protein of the transferrin and lactoferrin-iron transport systems. FbpA is conserved among neisserial species and is required for Neisseria gonorrhoeae to sustain growth on transferrin and lactoferrin. The identification of other putative TonB-dependent outer membrane transporters suggests that gonococci may employ other uncharacterized iron uptake systems that do not require FbpA. Previous work in our lab demonstrated that gonococcal strain FA19 utilizes iron from a number of xenosiderophores of the catecholate and hydroxamate classes. In this study we created conditional FbpA mutants to evaluate whether FbpA plays a role in the ability of gonococci to utilize iron from xenosiderophores. Strain FA19 was able to acquire iron from the xenosiderophores enterobactin and salmochelin in an FbpA-dependent and TonB-independent manner. We were also able to detect an extracellular population of FbpA indicating that FbpA may play a novel role in the internalization of iron in the absence of a dedicated transporter.
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Abshier, Patricia Alice. "Chlamydia Trachomatis and Neisseria Gonorrhoeae: Impact of Health Literacy on Prevalence." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1769.
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Millions of dollars are spent each year on preventing sexually transmitted diseases (STDs), yet the rates of chlamydia trachomatis (chlamydia) and neisseria gonorrhoeae (gonorrhea) infection continue to be high. Health literacy and its impact have been recognized in diabetes maintenance, control of hypertension, medical adherence, and reproductive health outcomes, yet no research has been conducted regarding the relationship between health literacy and chlamydia and gonorrhea prevalence. This study examined the relationship between health literacy scores and chlamydia and gonorrhea prevalence health literacy scores and reproductive health/STD knowledge, and reproductive health/STD knowledge and chlamydia and gonorrhea prevalence. Participants included 114 women over 18 years of age, who attended community health clinics in the northeastern United States. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine instrument, and reproductive health/STD knowledge was assessed using a self-administered questionnaire. Data analysis revealed an inverse correlation between lower health literacy scores and an increase in gonorrhea and combined chlamydia/gonorrhea prevalence. Findings also revealed a positive correlation between health literacy scores and reproductive health/STD knowledge scores. The results of this study suggest that service providers should consider the use of health literacy level with targeted reproductive health and STD messages as a tool to empower clients, decrease the prevalence of chlamydia and gonorrhea, and increase positive reproductive health outcomes.
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Yau, Chong-yee Miranda. "Comparison of two automated DNA amplification systems with culture for detection of Chlamydia trachomatis and Neisseria gonorrhoeae infections in symptomatic men." Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B23829709.
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邱莊儀 and Chong-yee Miranda Yau. "Comparison of two automated DNA amplification systems with culture fordetection of Chlamydia trachomatis and Neisseria gonorrhoeaeinfections in symptomatic men." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31969872.
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Simms, Amy Nicole. "Examination of Neisseria gonorrhoeae opacity protein expression during experimental murine genital tract infection /." Download the dissertation in PDF, 2005. http://www.lrc.usuhs.mil/dissertations/pdf/Simms2005.pdf.
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Van, Vuuren S. "Antibiotic resistance in neisseria gonorrhoeae." Thesis, 2014. http://hdl.handle.net/10210/11746.
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Chen, Po-Lin, and 陳柏齡. "Clinical Management for Gonorrhea and Gene Analysis of Macrolide Resistance in Neisseria Gonorrhoeae." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/05201985905889859130.
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碩士國立成功大學
臨床醫學研究所
96
Part I. Antimicrobial Therapy and Management for Gonorrhea in an Area with High-Level Antibiotic Resistance Abstract Background The choice of antimicrobial agents for gonorrhea is an important issue of public health in an area where the prevalence of drug resistance is high. Methods During 1999 to 2004, all Neisseria gonorrhoeae isolates causing clinical gonococcal disease were collected in the National Cheng Kung University Hospital. All stored isolates were subcultured in clinical microbiology laboratory and total 65 N. gonorrhoeae isolates were available. In vitro susceptibility tests of seven antimicrobial agents for available strains by Etest strips were performed and results were demonstrated in the previous study (1). Therein, we retrospectively reviewed and analyzed antimicrobial therapy of the 65 infected persons. Results Urethritis (89%) and pelvic inflammatory diseases (42%) were the most common presentation among males and females, respectively. In average, these patients needs more than 2 courses of antimicrobial therapy, and 3 visits for index infections in outpatient clinics. Clinical surveys of other sexually-transmitted diseases (STDs) were seen in 46% of patients, and 64% were reported to public health department by doctors. All isolates were not susceptible to penicillin, and tetracycline resistance rate was nearly 100%. Among patients receiving antibiotic treatment, 6.5%, 38.8% and 37% of them had in vitro active agents in the visit 1, 2, 3 respectively. Antimicrobial agents prescribed for gonococcal infections were tetracycline (30.6%), followed by cefuroxime (16.8%) and fluoroquinolones (including ciprofloxacin, lomefloxacin, ofloxacin and levofloxacin; 15.3%). Conclusions There is a lot of space for doctors to improve antibiotic treatment and management for gonorrhea. It is crucial to develop treatment guidelines according to regional antimicrobial resistances and educational programs to improve clinical care of STDs. According to drug susceptibility test, recommended antibiotics for gonorrhea include third-generation cephalosporin and spectinomycin. Part II. Screening of erm genes and mtrR mutations in Neisseria gonorrhoeae isolates with decreased macrolide susceptibility Abstract Background In a previous study in southern Taiwan, decreased erythromycin and azithromycin susceptibilities of N. gonorrhoeae were noted. Therefore, this study was undertaken to investigate the presence of various macrolide-resistant genes and mutation in N. gonorrhoeae isolates. Materials and methods Total 48 N. gonorrhoeae isolates collected during 1999 and 2004 were available for analysis. All isolates were examined the presence of erm(B), erm(C), erm(F), mef(A) genes by PCR amplification. Mutation in mtrR region was screened with PCR amplification and sequencing. Results Of the 48 clinical isolates, 31 (64.6%) were erythromycin intermediate resistance (MIC>1 mg/L). Forty-five (93.7%) isolates had the common adenine deletion in the mtrR promoter region. Among the 45 isolates, 12 were positive for erm(B) gene and 1 positive for erm(A) gene. No isolates possessed mef(A), erm(C), and erm(F) genes. Among 17 isolates with erythromycin MIC < 1.0 mg/L, 12 had mtrR mutation, 3 had concurrent mtrR mutation and erm(B) gene, and one carried erm(B) gene only. Of the 31 isolates with erythromycin MIC > 1.0 mg/L, two had no mutation or acquired resistant genes, 20 possessed only mtrR mutation, and the other 9 had concurrent mtrR mutation and ermB gene. Isolates with mtrR mutation and erm genes did not have higher erythromycin MIC level than those with only mtrR mutation. Serotyping with monoclonal antibody plus arbitrarily-primed PCR (AP-PCR) was a powerful tool to clarify the relationship among bacterial isolates. In the present study, there was no predominate clone among the N. gonorrhoeae isolates. Conclusion High prevalence of mtrR mutations was noted in N. gonorrhoeae isolates in southern Taiwan. Treatment with azithromycin for gonococcal infection should be careful due to previous treatment failure report and potential emergence of drug resistance.
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Magooa, Mahlape Precious. "Detection and molecular epidemiology of ciprofloxacin-resistant Neisseria gonorrhoeae, using a real-time polymerase chain reaction (PCR)." Thesis, 2011. http://hdl.handle.net/10539/9187.
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MSc (Med), Clinical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of the WitwaterstrandEmergence and spread of resistance to ciprofloxacin among Neisseria gonorrhoeae strains has reduced the options of effective treatment for gonococcal infections and has become a concern worldwide. Up until 2008, ciprofloxacin was recommended first-line therapy for treatment of presumptive N. gonorrhoeae infections in South Africa. At the time this MSc project was conceived, ciprofloxacin was still used as first-line therapy for presumptive gonococcal infections. A real-time polymerase chain reaction (PCR) assay was used to detect ciprofloxacin-resistant N. gonorrhoeae in DNA extracted from non-invasive urine samples collected as part of the national microbiological surveillance (NMS) programme during 2006-2007. The molecular epidemiology of ciprofloxacinresistant Neisseria gonorrhoeae was investigated by sequencing the quinolone resistance determining regions (QRDR) of the gyrA and parC genes of N. gonorrhoeae and performing N. gonorrhoeae multi-antigen sequence typing (NGMAST). As part of the NMS program for sexually transmitted infections (STIs) urine and urethral swabs were collected from men presenting with urethral discharge at primary health care clinics in Johannesburg (Gauteng), Cape Town (Western Cape) and Kimberley (Northern Cape). Urine samples and cultured N. gonorrhoeae isolates from 2006-2007 were stored at -700C and available for this study. Gonococci, previously isolated from urethral swabs, were subcultured directly onto New York City media. Isolate identity was re-confirmed by typical colony morphology and biochemical tests. Urine samples from Johannesburg were tested in order to develop the real-time PCR protocol. Subsequently, paired urethral swab DNA and N. gonorrhoeae cultures were tested from NMS patients recruited in Kimberley and Cape Town. Where possible, the PCR assay results were compared with paired antibiotic susceptibility data for ciprofloxacin. Quinolone resistance determining regions (QRDR) for gyrA and parC were screened for known point mutations associated with resistance to ciprofloxacin. Detection of mutations by the real-time PCR assay generally agreed with the phenotype of either decreased susceptibility or resistance to ciprofloxacin. All ciprofloxacin resistant gonococcal isolates had the same gyrA and parC mutations, which initially suggested that quinolone resistant N. gonorrhoeae (QRNG) in Kimberley, Cape Town and Johannesburg, may be attributed to the spread of a single clone. The use of a more discriminatory typing scheme, Neisseria gonorrhoeae Multi-Antigen Sequence Typing (NG-MAST) genotyping, revealed that ciprofloxacin resistant gonococcal isolates in Johannesburg and Cape Town were heterogeneous, with sequence type (ST) 217 being most prevalent in both cities (5/16, Johannesburg; 7/11, Cape Town). In contrast, all eight QRNG isolates from Kimberley were typed as ST 533. The use of molecular methods allowed ciprofloxacin antimicrobial susceptibility determination by PCR in non-invasive specimens. This is useful in situations where bacterial cultures are unavailable or die before antimicrobial susceptibility testing can be performed. Molecular assays to detect ciprofloxacin resistance may guide physicians as to the most ideal antimicrobial combinations for individual patient treatment. As a result of emerging widespread resistance gonococci to ciprofloxacin, in 2008, the Department of Health recommended that ciprofloxacin be removed as a first line therapy in the South African national sexually transmitted infections treatment guidelines for treatment of urethritis, cervicitis and their complications. Although ciprofloxacin is no longer used as a first-line therapy to treat gonorrhoea within our country, it may still be used in cases of severe penicillin allergy or as part of multi-drug therapy for gonococcal infections in the future. The ability to detect ciprofloxacin resistance by real-time PCR will be a useful technique in such situations.
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Francis, Ian Patrick. "The characterization of novel transgenic murine models of Neisseria gonorrhoeae infection and development of a natural outer membrane vesicle anti-gonococcal vaccine candidate." Thesis, 2018. https://hdl.handle.net/2144/29993.
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Untreatable gonorrhea, caused by fully antimicrobial resistant Neisseria gonorrhoeae (GC), is a major global health threat. While a vaccine would greatly help address this crisis, development of a GC vaccine is complicated by the lack of lab models of symptomatic gonorrhea. We hypothesized that overt disease in animal models of gonorrhea is limited by the human-restriction of gonococcal virulence factors, and the impact of the reproductive hormone cycle (estrus and diestrus phases). We tested these hypotheses by examining the host response to infection in transgenic mice expressing targets of bacterial adhesion, human carcinoembryonic antigen-related cell adhesion molecules (hCEACAMs), in uterine versus vaginal infections, and in different phases of the reproductive cycle (estrus and diestrus phases). hCEACAM expression most impacted estrus phase infections, prolonging colonization in vaginal infection and inducing greater inflammation in uterine. Reproductive phase greatly influenced host response to uterine infection as diestrus infection was more inflammatory than estrus. Phase differences in uterine infection were driven by greater activation of a chemokine-centric common anti gonococcal response and unique induction of type 1 interferons in diestrus. These findings suggest that symptomatic uterine and vaginal GC infection can be modeled by transcervically infected wild-type diestrus mice and transgenic, vaginally-infected estrus mice, respectively.
A novel approach to GC vaccine development is also needed. Mono-antigenic vaccines have failed to produce immunity suggesting a poly-antigenic antigen, like natural outer membrane vesicles (nOMVs) may be necessary. It has been shown that any GC vaccine must lack the bacterioprotective antigen, reduction modifiable protein (RMP), and no such nOMV has been previously described. Here we report successful isolation of RMP-deficient nOMVs through sequential size and weight restrictive filtration. Vesicle morphology, proteomics, and bioactivity was characterized via various methods. nOMVs were found to be consistent in size, shape and antigenic load. As antigens, nOMVs induced high serum titers and measurable vaginal levels of antigen and GC specific IgG that recognized several nOMV immunogens supporting the vaccine potential of GC nOMVs. These findings lay the groundwork for protective studies of nOMV vaccines in novel models of active gonorrhea moving the field closer to discovering the mechanism of protective anti-gonococcal immunity.
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"Epidemiologic Approaches to Understanding Gonorrhea Transmission Dynamics and the Development of Antimicrobial Resistance." Thesis, 2016. http://hdl.handle.net/10388/ETD-2016-02-2422.
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Globally, the incidence of infection caused by Neisseria gonorrhoeae is the second highest among the bacterial sexually transmitted infections. In Canada, declining rates during the 1990s suggested progress toward curbing gonorrhea; however, those have been increasing since 1999, with rates in Saskatchewan among the highest in the country. Infection can cause serious complications in men and women, and reported resistance to third-generation cephalosporins could lead to potentially untreatable infections. Increased understanding of gonorrhea transmission dynamics, sexual networks, and predictors of antimicrobial resistance development is needed to inform the development of improved approaches to prevention and treatment.
The research presented herein draws upon data from Shanghai, China, and Saskatchewan, Canada, to compare and contrast varying epidemiologic approaches to enhancing understanding of gonorrhea in the two settings. Using traditional statistical approaches, multi-level statistical modeling, social network analysis, and dynamic simulation modeling, questions related to sexual behavior, partner presentation, and antimicrobial resistance development are explored. Each technique is evaluated for its potential contribution to overall understanding of the issues related to the ongoing gonorrhea epidemic, globally, and in Saskatchewan.
The relative strengths and limitations of the application of the analytical approaches in the different settings are described. Socio-demographic characteristics provided useful indicators of antimicrobial resistant infection among patients with gonorrhea from Shanghai. Further, socio-demographic characteristics were also useful for predicting presentation of a partner for testing and treatment and the use of condoms during intercourse, among this study population. In Saskatchewan, socio-demographic characteristics were useful in predicting coinfection with gonorrhea and chlamydia at the time of diagnosis as well as repeat infection with gonorrhea. Social network analysis of the Saskatchewan dataset provided little additional understanding of the gonorrhea epidemic in the province. This result was largely related to how STI data are collected and stored in the province. The utility of dynamic simulation modeling to investigate the potential impact of antimicrobial resistance in Saskatchewan was also limited due to the same data constraints. However, the insight gained from the model building process and findings from the working model did offer a starting point for conversations around the best ways to postpone the development of antimicrobial resistance in N. gonorrhoeae in Saskatchewan, as well as contribute additional information about how the ways in which STI data are collected and stored in the province considerably restrict the applicability of otherwise powerful epidemiologic tools.
With persistently high rates of disease transmission, and the threat of untreatable infections due to antimicrobial resistance, N. gonorrhoeae remains a substantial public health threat locally and globally. The research presented herein describes various approaches to understanding and controlling this disease, applied in contrasting settings. There are a wide variety of elements that should be considered when choosing the appropriate tool(s) to address gonorrhea in a given population; there is no “one size fits all” solution. The local epidemiology of disease, cultural and behavioural norms, the characteristics of the notifiable disease reporting and information systems, and the availability of suitable data all affect the relative strengths and weaknesses of the available analytic methods and disease control approaches.
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Lin, Chia-Wei, and 林家偉. "Investigation of the antimicrobial usage for the treatment of gonorrhea and the epidemiology of antimicrobial resistance in Neisseria gonorrhoeae in Tainan, Taiwan." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/22443540750765132618.
Full textAbstract:
碩士國立成功大學
公共衛生研究所
94
A physician-based sentinel surveillance on Neisseria gonorrhoeae (GC) infection has identified hidden epidemic of gonorrhea in a southern Taiwan city (Tainan), where there is no standard national treatment guideline and no definite patterns of antimicrobial resistance are available currently. Therefore, we conducted a study, and the goals of this study include: (1) to determine quinolone resistance in GC positive urine specimens from the surveillance by molecular techniques; and (2) to determine the antimicrobial resistance profiles in GC isolates from a medical center in the same city. In addition, we would also identify current antimicrobial prescriptions for GC infections in Tainan. Quinolone resistance-determining region (QRDR) of gyrA and parC were amplified by PCR on 80 GC-positive urine specimens from the surveillance during November of 2003 and December of 2004 and 67 isolates were obtained from the medical center during 1999 and 2004. Then, the amplicons were sequenced directly. Sequences of QRDR were compared to published mutations associated with decreased susceptibility or resistance to fluoroquinolones in GC. Novel mutations were identified by comparing sequences in published literature and GenBank. Antimicrobial resistance profiles (penicillin, tetracycline, ofloxacin, norfloxacin, erythromycin, azithromycin, ceftriaxone, cefixime, and trimethoprim/sulphamethoxazole) of GC isolates were performed by Etest. The antimicrobial prescription for GC infections were obtained medical records of GC patients from a medical center in Tainan and from National health insurance ambulatory claim data of Feb. to Mar. 2000, Feb. to Mar. 2001 and Feb. to Mar. 2002 respectively in the same city. Overall, 90.8% (148/163) specimens had known mutations in QRDR with decreased susceptibility or resistance to fluoroquinolones. Majority (84/148) of them possessed mutations in both genes. Noticeably, two amino acid mutations were identified for the first time from two patients (gyrA:Ser91→Leu, parC:Ser87→Cys). The antimicrobial resistance profiles were available on 67 isolates, all were resistant to trimethoprim/sulphamethoxazole and Penicillin, followed by Tetracycline (97%), Fluoroquinolones (85%), and Erythromycin (20.9%). All isolates were susceptible to third-generation of Cephalosporins, Azithromycin and Spectinomycin. According to the medical records documented in the prescriptions, the top three antimicrobials for GC infection in order were Tetracycline (43.3%), Cephalosporins (24.4%), Fluoroquinolones (22.2%). We can also found a similar result if we combined the antimicrobial prescriptions from medical center, regional & district hospitals in the NHI database. Differently, the most use of antimicrobial for GC was Cephalosporins (36.8%) in clinics from the database of National Health Insurance. High mutation rates in QRDR coupling with low susceptibility rates to commonly used prescribed antimicrobials for treatment of gonorrhea in this southern Taiwan city indicate that an urgent need for a national treatment guideline and an effective molecular epidemiologic surveillance on GC infection and resistance patterns is warranty before the hidden epidemic becomes out of control.