Antimicrobial Resistance of Neisseria gonorrhoeae Isolates from High-Risk Men in Johannesburg, South Africa

ABSTRACT Neisseria gonorrhoeae antimicrobial drug resistance has emerged worldwide; however, the situation in sub-Saharan Africa is not well documented. We investigated the molecular epidemiology and occurrence of antimicrobial resistance in Neisseria gonorrhoeae infections in two core transmission groups of men in Johannesburg, South Africa. We recruited men who have sex with men (MSM) presenting with urethral discharge and men with recurrent episodes of urethral discharge. Molecular testing and culture for N. gonorrhoeae were performed, followed by antimicrobial susceptibility testing. Whole-genome sequencing (WGS) was used to identify resistance-conferring mutations and to determine the genetic relatedness of the isolates. In all, 51 men were recruited; 42 (82%) had N. gonorrhoeae infections. Most gonococcal isolates were resistant to ciprofloxacin (78%) and tetracycline (74%); 33% were penicillin resistant. All gonococcal isolates were susceptible to cephalosporins and spectinomycin. Azithromycin resistance was observed in 4 (15%) isolates (epidemiological cutoff), all with mutations in the mtrR promoter region. Most of the isolates (19/27) harbored the gonococcal genetic island, which is associated with antimicrobial resistance. WGS revealed a diverse epidemic with mostly novel NG-STAR (70%) and NG-MAST (70%) sequence types. Thus, we demonstrate a high prevalence of antimicrobial resistance in Neisseria gonorrhoeae strains obtained from high-risk men in South Africa. The introduction of diagnostics and scale-up of surveillance are warranted to prevent the emergence of multidrug-resistant infections.

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Antimicrobial resistance mechanisms, MLST and NG-STAR sequence types of diverse Neisseria gonorrhoeae isolates in KwaZulu-Natal, South Africa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00759-21 ◽

2021 ◽

Author(s):

Nireshni Mitchev ◽

Ravesh Singh ◽

Mushal Allam ◽

Stanford Kwenda ◽

Arshad Ismail ◽

...

Keyword(s):

South Africa ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Point Mutations ◽

Resistance Mechanisms ◽

Public Healthcare ◽

Multiple Sequence ◽

Genotypic Analysis ◽

Kwazulu Natal ◽

Sequence Types

Objective: Antimicrobial resistance (AMR) is a major challenge to managing infectious diseases. Africa has the highest incidence of gonorrhoea but there is a lack of comprehensive data from sparse surveillance programs. This study investigated the molecular epidemiology and AMR profiles of Neisseria gonorrhoeae isolates in KwaZulu-Natal province (KZN), South Africa. Methods: Repository isolates, from patients attending public healthcare clinics for STI care, were used for phenotypic and genotypic analysis. Etest® was performed to determine antimicrobial susceptibility. Whole-genome sequencing (WGS) was used to determine epidemiology and to predict susceptibility by detecting resistance-associated genes and mutations. Results: Among the 61 isolates, multiple sequence types were identified. Six isolates were novel as determined by multilocus sequence typing. N.gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) determined 48 sequence types, of which 35 isolates had novel antimicrobial profiles. Two novel penA alleles and eight novel mtrR alleles were identified. Point mutations were detected in gyrA , parC , mtrR , penA , ponA and porB1 . This study revealed a high prevalence of AMR (penicillin 67%, tetracycline 89% and ciprofloxacin 52%). However, spectinomycin, cefixime, ceftriaxone and azithromycin remained 100% effective. Conclusion: This study is one of the first to comprehensively describe the epidemiology and AMR of N. gonorrhoeae in KZN, South Africa and Africa, using WGS. KZN has a wide strain diversity and most of these sequence types have been detected in multiple countries, however more than half of our isolates have novel antimicrobial profiles. Continued surveillance is crucial to monitor the emergence of resistance to cefixime, ceftriaxone and azithromycin.

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Genotypic and Phenotypic Characterization of Antimicrobial Resistance in Neisseria gonorrhoeae: a Cross-Sectional Study of Isolates Recovered from Routine Urine Cultures in a High-Incidence Setting

mSphere ◽

10.1128/msphere.00373-19 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 1

Author(s):

Adam L. Bailey ◽

Robert F. Potter ◽

Meghan A. Wallace ◽

Caitlin Johnson ◽

Gautam Dantas ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Susceptibility Testing ◽

Clinical Laboratory ◽

Phenotypic Characterization ◽

First Line ◽

Content Type ◽

Gradient Diffusion

ABSTRACT The objectives of this study were to perform genomic and phenotypic characterization of antimicrobial resistance in Neisseria gonorrhoeae isolates recovered from urine samples from patients in St. Louis, MO, USA. Sixty-four clinical isolates were banked over a 2-year period and subjected to antimicrobial susceptibility testing (AST) by Kirby-Bauer disk diffusion (penicillin, tetracycline, cefuroxime, and ciprofloxacin) and gradient diffusion (tetracycline, doxycycline, azithromycin, ceftriaxone, cefixime, ciprofloxacin, gemifloxacin, and delafloxacin). The medical records for the patients were evaluated to determine the demographics, location, and prescribed treatment regimen. Isolate draft genomes were assembled from Illumina shotgun sequencing data, and resistance determinants were identified by ResFinder and PointFinder. Of the 64 isolates, 97% were nonsusceptible to penicillin, with resistant isolates all containing the blaTEM-1b gene; 78 and 81% of isolates were nonsusceptible to tetracycline and doxycycline, respectively, with resistant isolates all containing the tet(M) gene. One isolate was classified as non-wild-type to azithromycin, and all isolates were susceptible to ceftriaxone; 89% of patients received this combination of drugs as first-line therapy. Six percent of isolates were resistant to ciprofloxacin, with most resistant isolates containing multiple gyrA and parC mutations. Correlation between disk and gradient diffusion AST devices was high for tetracycline and ciprofloxacin (R2 > 99% for both). The rates of N. gonorrhoeae antibiotic resistance in St. Louis are comparable to current rates reported nationally, except ciprofloxacin resistance was less common in our cohort. Strong associations between specific genetic markers and phenotypic susceptibility testing hold promise for the utility of genotype-based diagnostic assays to guide directed antibiotic therapy. IMPORTANCE Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is most commonly diagnosed using a DNA-based detection method that does not require growth and isolation of N. gonorrhoeae in the laboratory. This is problematic because the rates of antibiotic resistance in N. gonorrhoeae are increasing, but without isolating the organism in the clinical laboratory, antibiotic susceptibility testing cannot be performed on strains recovered from clinical specimens. We observed an increase in the frequency of urine cultures growing N. gonorrhoeae after we implemented a total laboratory automation system for culture in our clinical laboratory. Here, we report on the rates of resistance to multiple historically used, first-line, and potential future-use antibiotics for 64 N. gonorrhoeae isolates. We found that the rates of antibiotic resistance in our isolates were comparable to national rates. Additionally, resistance to specific antibiotics correlated closely with the presence of genetic resistance genes, suggesting that DNA-based tests could also be designed to guide antibiotic therapy for treating gonorrhea.

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Time to scale up PrEP beyond the highest-risk populations? Modelling insights from high-risk women in sub-Saharan Africa

Sexually Transmitted Diseases ◽

10.1097/olq.0000000000001253 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Hannah Grant ◽

Gabriela B. Gomez ◽

Katharine Kripke ◽

Ruanne V. Barnabas ◽

Charlotte Watts ◽

...

Keyword(s):

High Risk ◽

Scale Up ◽

Sub Saharan Africa ◽

High Risk Women ◽

Sub Saharan

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Are smallholder farmers’ perceptions of climate variability supported by climatological evidence? Case study of a semi-arid region in South Africa

International Journal of Climate Change Strategies and Management ◽

10.1108/ijccsm-01-2020-0007 ◽

2020 ◽

Vol 12 (5) ◽

pp. 571-585 ◽

Cited By ~ 1

Author(s):

Maropene Tebello Rapholo ◽

Lawrence Diko Makia

Keyword(s):

South Africa ◽

Climate Variability ◽

Arid Region ◽

Smallholder Farmers ◽

Linear Trend ◽

Meteorological Data ◽

Sub Saharan Africa ◽

Content Type ◽

Semi Arid Region ◽

Semi Arid

Purpose Literature contends that not much is known about smallholder farmers’ perceptions of climate variability and the impacts thereof on agricultural practices in Sub-Saharan Africa and South Africa in particular. The purpose of this study is to examine the perceptions of smallholder farmers from Botlokwa (a semi-arid region in South Africa) on climate variability in relation to climatological evidence. Design/methodology/approach The study area is in proximity to a meteorological station and comprises mainly rural farmers, involved in rain-fed subsistence agriculture. Focus group discussions and closed-ended questionnaires covering demographics and perceptions were administered to 125 purposely sampled farmers. To assess farmers’ perceptions of climate variability, their responses were compared with linear trend and variability of historical temperature and rainfall data (1985-2015). Descriptive statistics were used to provide insights into respondents’ perceptions. Findings About 64% of the farmers perceived climate variability that was consistent with the meteorological data, whereas 36% either held contrary observations or were unable to discern. Age, level of education, farming experience and accessibility to information influenced the likelihood of farmers to correctly perceive climate variability. No significant differences in perception based on gender were observed. This study concludes that coping and adaption strategies of over one-third of the farmers could be negatively impacted by wrong perceptions of climate variability. Originality/value This study highlights discrepancies in perceptions among farmers with similar demographic characteristics. To guarantee sustainability of the sector, intervention by government and other key stakeholders to address underlying factors responsible for observed discrepancies is recommended.

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Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance, a Novel Antimicrobial Resistance Multilocus Typing Scheme for Tracking Global Dissemination of N. gonorrhoeae Strains

Journal of Clinical Microbiology ◽

10.1128/jcm.00100-17 ◽

2017 ◽

Vol 55 (5) ◽

pp. 1454-1468 ◽

Cited By ~ 73

Author(s):

W. Demczuk ◽

S. Sidhu ◽

M. Unemo ◽

D. M. Whiley ◽

V. G. Allen ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Dna Sequences ◽

Diversity Index ◽

23S Rrna ◽

Content Type ◽

Typing Scheme ◽

Resistance Determinants ◽

Index Value ◽

User Friendly

ABSTRACTA curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants inNeisseria gonorrhoeaewas developed and is publicly accessible (https://ngstar.canada.ca). TheN. gonorrhoeaeSequence Typing for Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (penA,mtrR,porB,ponA,gyrA,parC, and 23S rRNA) associated with resistance to β-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entirepenAsequence, combining the historical nomenclature forpenAtypes I to XXXVIII with novel nucleotide sequence designations; the fullmtrRsequence and a portion of its promoter region; portions ofponA,porB,gyrA, andparC; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (n= 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (n= 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval [CI] = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (n= 100; 13.0%), ST-42 and ST-91 (n= 45; 5.9%), ST-64 (n= 44; 5.72%), and ST-139 (n= 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (n= 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (n= 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (n= 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (n= 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistantN. gonorrhoeaestrains.

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Prospects for Africa's economies to end-2016

Emerald Expert Briefings ◽

10.1108/oxan-db211521 ◽

2016 ◽

Keyword(s):

South Africa ◽

Southern Africa ◽

Commodity Price ◽

Sub Saharan Africa ◽

Gdp Growth ◽

Content Type ◽

Idiosyncratic Shocks ◽

Sub Saharan ◽

Eastern And Southern Africa

Subject Prospects for Africa's economies to end-2016. Significance The IMF's most recent forecast of 3% GDP growth for sub-Saharan Africa (SSA) in 2016 represents a significant cut from the 4.25% it expected in October 2015. This is a consequence of sharp slowdowns in the region's two largest economies, Nigeria and South Africa, droughts in previously buoyant economies (notably in eastern and southern Africa), a variety of idiosyncratic shocks and a prolonged commodity price downturn.

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Multiplex Real-Time PCR Assay with High-Resolution Melting Analysis for Characterization of Antimicrobial Resistance in Neisseria gonorrhoeae

Journal of Clinical Microbiology ◽

10.1128/jcm.03354-15 ◽

2016 ◽

Vol 54 (8) ◽

pp. 2074-2081 ◽

Cited By ~ 19

Author(s):

Valentina Donà ◽

Sara Kasraian ◽

Agnese Lupo ◽

Yuvia N. Guilarte ◽

Christoph Hauser ◽

...

Keyword(s):

High Resolution ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Real Time ◽

Sensitivity And Specificity ◽

Real Time Pcr ◽

High Resolution Melting ◽

Health Concern ◽

Content Type ◽

Resistance To Antibiotics

Resistance to antibiotics used againstNeisseria gonorrhoeaeinfections is a major public health concern. Antimicrobial resistance (AMR) testing relies on time-consuming culture-based methods. Development of rapid molecular tests for detection of AMR determinants could provide valuable tools for surveillance and epidemiological studies and for informing individual case management. We developed a fast (<1.5-h) SYBR green-based real-time PCR method with high-resolution melting (HRM) analysis. One triplex and three duplex reactions included two sequences forN. gonorrhoeaeidentification and seven determinants of resistance to extended-spectrum cephalosporins (ESCs), azithromycin, ciprofloxacin, and spectinomycin. The method was validated by testing 39 previously fully characterizedN. gonorrhoeaestrains, 19 commensalNeisseriaspecies strains, and an additional panel of 193 gonococcal isolates. Results were compared with results of culture-based AMR determination. The assay correctly identifiedN. gonorrhoeaeand the presence or absence of the seven AMR determinants. There was some cross-reactivity with nongonococcalNeisseriaspecies, and the detection limit was 103to 104genomic DNA (gDNA) copies/reaction. Overall, the platform accurately detected resistance to ciprofloxacin (sensitivity and specificity, 100%), ceftriaxone (sensitivity, 100%; specificity, 90%), cefixime (sensitivity, 92%; specificity, 94%), azithromycin (sensitivity and specificity, 100%), and spectinomycin (sensitivity and specificity, 100%). In conclusion, our methodology accurately detects mutations that generate resistance to antibiotics used to treat gonorrhea. Low assay sensitivity prevents direct diagnostic testing of clinical specimens, but this method can be used to screen collections of gonococcal isolates for AMR more quickly than current culture-based AMR testing.

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Escherichia coliSequence Type 410 Is Causing New International High-Risk Clones

mSphere ◽

10.1128/msphere.00337-18 ◽

2018 ◽

Vol 3 (4) ◽

pp. e00337-18 ◽

Cited By ~ 51

Author(s):

Louise Roer ◽

Søren Overballe-Petersen ◽

Frank Hansen ◽

Kristian Schønning ◽

Mikala Wang ◽

...

Keyword(s):

Escherichia Coli ◽

High Risk ◽

Antimicrobial Resistance ◽

Sequence Type ◽

Recurrent Infections ◽

Content Type ◽

E Coli ◽

The Past ◽

Carbapenemase Gene ◽

Globally Distributed

ABSTRACTEscherichia colisequence type 410 (ST410) has been reported worldwide as an extraintestinal pathogen associated with resistance to fluoroquinolones, third-generation cephalosporins, and carbapenems. In the present study, we investigated national epidemiology of ST410E. coliisolates from Danish patients. Furthermore,E. coliST410 was investigated in a global context to provide further insight into the acquisition of the carbapenemase genesblaOXA-181andblaNDM-5of this successful lineage. From 127 whole-genome-sequenced isolates, we reconstructed an evolutionary framework ofE. coliST410 which portrays the antimicrobial-resistant clades B2/H24R, B3/H24Rx, and B4/H24RxC. The B2/H24R and B3/H24Rx clades emerged around 1987, concurrently with the C1/H30R and C2/H30Rx clades inE. coliST131. B3/H24Rx appears to have evolved by the acquisition of the extended-spectrum β-lactamase (ESBL)-encoding geneblaCTX-M-15and an IncFII plasmid, encoding IncFIA and IncFIB. Around 2003, the carbapenem-resistant clade B4/H24RxC emerged when ST410 acquired an IncX3 plasmid carrying ablaOXA-181carbapenemase gene. Around 2014, the clade B4/H24RxC acquired a second carbapenemase gene,blaNDM-5, on a conserved IncFII plasmid. From an epidemiological investigation of 49E. coliST410 isolates from Danish patients, we identified five possible regional outbreaks, of which one outbreak involved nine patients withblaOXA-181- andblaNDM-5-carrying B4/H24RxC isolates. The accumulated multidrug resistance inE. coliST410 over the past two decades, together with its proven potential of transmission between patients, poses a high risk in clinical settings, and thus,E. coliST410 should be considered a lineage with emerging “high-risk” clones, which should be monitored closely in the future.IMPORTANCEExtraintestinal pathogenicEscherichia coli(ExPEC) is the main cause of urinary tract infections and septicemia. Significant attention has been given to the ExPEC sequence type ST131, which has been categorized as a “high-risk” clone. High-risk clones are globally distributed clones associated with various antimicrobial resistance determinants, ease of transmission, persistence in hosts, and effective transmission between hosts. The high-risk clones have enhanced pathogenicity and cause severe and/or recurrent infections. We show that clones of theE. coliST410 lineage persist and/or cause recurrent infections in humans, including bloodstream infections. We found evidence of ST410 being a highly resistant globally distributed lineage, capable of patient-to-patient transmission causing hospital outbreaks. Our analysis suggests that the ST410 lineage should be classified with the potential to cause new high-risk clones. Thus, with the clonal expansion over the past decades and increased antimicrobial resistance to last-resort treatment options, ST410 needs to be monitored prospectively.

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Typing of Neisseria gonorrhoeae Isolates in Shenzhen, China, from 2014 to 2018 Reveals the Shift of Genotypes Significantly Associated with Antimicrobial Resistance

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02311-20 ◽

2021 ◽

Vol 65 (5) ◽

Author(s):

Yizhun Li ◽

Yamei Li ◽

Leshan Xiu ◽

Yaling Zeng ◽

Chi Zhang ◽

...

Keyword(s):

Logistic Regression ◽

Antimicrobial Resistance ◽

Neisseria Gonorrhoeae ◽

Molecular Epidemiology ◽

Important Data ◽

Content Type ◽

Future Studies ◽

Ideal Tool ◽

Global Threat ◽

Sequence Types

ABSTRACT The growing antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. Molecular typing is an ideal tool to reveal the association between specific genotypes and resistance phenotypes that provide effective data for tracking the transmission of resistant clones of N. gonorrhoeae. In our study, we aimed to describe the molecular epidemiology of AMR and the distribution of resistance-associated genotypes in Shenzhen, China, during 2014 to 2018. In total, 909 isolates were collected from Shenzhen from 2014 to 2018. Two typing schemes, multilocus sequence typing (MLST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR), were performed for all isolates. The distribution of resistance-associated genotypes was described using goeBURST analysis combined with logistic regression data. Among 909 isolates, sequence type 8123 (ST8123), ST7363, ST1901, ST7365, and ST7360 were the most common MLST sequence types, and ST348, ST2473, ST497, and ST199 were the most prevalent NG-STAR STs. Logistic regression analysis showed that NG-STARST497, MLSTST7365, and MLSTST7360 were typically associated with decreased susceptibility to ceftriaxone. Furthermore, the internationally spreading extended-spectrum cephalosporin (ESC)-resistant clone MLSTST1901 has been prevalent since at least 2014 in Shenzhen and showed a significant increase during 2014 to 2018. Additionally, MLSTST7363 owns the potential to become the next internationally spreading ceftriaxone-resistant ST. In conclusion, we performed a comprehensive epidemiological study to explore the correlation between AMR and specific STs, which provided important data for future studies of the molecular epidemiology of AMR in N. gonorrhoeae. Besides, these findings provide insight for adjusting surveillance strategies and therapy management in Shenzhen.

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New players join race for offensive cyber abilities

Emerald Expert Briefings ◽

10.1108/oxan-db236921 ◽

2018 ◽

Keyword(s):

South Africa ◽

Developing Countries ◽

High Risk ◽

Personal Data ◽

Corporate Investment ◽

Political Pressure ◽

Content Type

Subject Lesser-known cyber players. Significance The proliferation of offensive cyber capabilities continues beyond the headline-making actors. Many states are trying to capitalise on this relatively new domain of competition, including Brazil, South Africa, India and Vietnam. Impacts Businesses investing or partnering with entities in Vietnam face a particularly high risk of being targeted by state-linked actors. Corporate investment in cybersecurity will rise in nearly all developing countries, albeit slowly and unevenly. Theft of digital personal data will fuel political pressure for proactive cybersecurity strategies.

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