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2Y^K 614.212/618.2
THE DANGER OF ANTIBIOTIC RESISTANCE OF NEISSERIA GONORRHOEAE WORLDWIDE
*D.M. Amangeldy, A.T. Dzhumabekov, B.A. Zhumabekova
Kazakhstan medical University "KSPH", Almaty, Kazakhstan
Abstract
Gonorrhea is a sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae. According to the WHO, the number of new cases of sexually transmitted diseases in 2020 reached 374 million, a quarter of which were caused by gonorrhea - 82.4 million, a 5.64% increase compared to 2012 when there were 78 million new cases.
Introduction. Gonorrhea remains one of the most common sexually transmitted infections worldwide [1], the causative agent of which is the gram-negative bacteria Neisseria gonorrhoeae.
Currently, gonorrhea poses a significant threat to public health due to the rapid increase in the incidence and resistance of the microorganism to antibiotics [2].
More than 78 million cases are reported worldwide each year, and treatment options are limited in low-income countries and marginalized groups in richer countries [3]. Gonorrhea continues to pose a serious threat to global public health: the World Health Organization (WHO) estimates that 78.31 million new cases of the disease were reported in 2008 among people aged 15 to 49 years. According to the Centers for Disease Control and Prevention (CDC), gonorrhea is the second most common bacterial disease in the United States [4]. In 2015, about 395,200 cases of gonorrhea were reported, which is 27% more than in 2012.
Incidence is higher in resource-limited countries-for example, incidence is 50 cases per 1,000 men and 42 cases per 1,000 women in sub-Saharan Africa, compared with 9 cases per 1,000 men and 6 cases per 1,000 women in North America and Europe [5]. In the United States, incidence in 2018 was 600000 cases - an increase of more than 80% over the historical low in 2009. The United Kingdom has similar numbers (up 26% in 2018 from 2017 and at its highest level since 1978) and Australia (up 63% in 5 years) [5-7].
The increase is due to the spread among young men and men who have sex with men [89]. N. gonorrhoeae infects and leads to inflammation in various mucosal tissues including the cervix, urethra, rectum, pharynx, and conjunctiva and subsequently can lead to the spread to
other locations [10]. Urethral infection is the most common and often leads to discharge and dysuria. In women, cervical infection is often asymptomatic [11]. N. gonorrhoeae can progress to pelvic inflammatory disease (PID) [12], what can lead to infertility, chronic pelvic pain and ectopic pregnancy - consequences that affect a significant proportion of women infected (18%, 29% and 0.6% respectively) [13] with the worst consequences being delayed care and repeated episodes of PID.
Key words: neisseria gonorrhoeae, cephalosporins (ESCs), The Gonococcal Isolate Surveillance Project (GISP).
Objectives
To evaluate worldwide tendency spreading of Neisseria gonorrhoeae resistant strains in 21 century based scientific publications.
Materials and methods
We have conducted a literature review from 2014-2021 of incidence Neisseria gonorrhoeae antibiotic resistant strains, ant trends of possible changes in future.
Current stability position
As predicted by the U.S. Centers for Disease Control and Prevention [12] in 2012, N. gonorrhoeae has become a superinfection and is an urgent public health threat.
Increasingly, gonococcal strains resistant to extended-spectrum cephalosporins (ESCs) and azithromycin are being identified, which can lead to a situation where gonorrhea is not treatable. In fact, strains of N. Gonorrhoeae H041 (MIC of ceftriaxone 2 mg/L), F89 (MIC of ceftriaxone 1 mg/L), and A8806 (MIC of ceftriaxone 0.5 mg/L) with high levels of ceftriaxone resistance have been isolated from patients in Japan [13], France [14] and Australia [15], respectively. Moreover, a new ceftriaxone- and multidrug-resistant N. gonorrhoeae was recently isolated in Japan [16]. At the same time, another study in Canada [17] showed that the proportion of isolates with reduced sensitivity to cephalosporins decreased significantly between 2011 and 2014, while resistance to azithromycin increased significantly during the same period.
This study concluded that continued monitoring of gonococcal antimicrobial susceptibility is necessary for the relevance of treatment recommendations to slow the spread of isolates with decreased sensitivity to cephalosporins and resistance to azithromycin. Also, the first case of failure of standard dual antimicrobial treatment for gonorrhea was recently reported in the United Kingdom [18]. Results of AMP sensitivity tests showed that the strain was resistant to ceftriaxone, azithromycin, cefixime, cefotaxime, penicillin, tetracycline, and ciprofloxacin,
but sensitivity to spectinomycin was present. As these reports show, the treatment of gonococcal infection is in serious jeopardy because of the emergence of antimicrobial resistance.
With this in mind, governments around the world have created data collection programs to study how this bacterium develops resistance and manifests itself at the community level [19]. The three most common programs are the Gonococcal Resistance to Antimicrobial Resistance Surveillance Program (GRASP) in the United Kingdom
("https://www.gov.uk/government/publications/gonococcal-resistance-to-antimicrobialssurveillance-program-grasp-report), the Gonococcal Surveillance Project (GISP) in the United States (https://www.cdc.gov/std/gisp/), and the European Gonococcal Resistance Surveillance Program (Euro-GASP)
("http://ecdc.europa.eu/en/healthtopics/gonorrhoea/response-plan/pages/strengthening-antimicrobialsurveillance.aspx"). All three programs have a common goal: to identify the emergence of any AMRs that might threaten the efficacy of existing first-line treatments. Reports from all three programs provide insight into how antibiotic resistance develops among strains of N. Gonorrhoeae [20].
■Ciprofloxacin ■Azithromycin Ceftriaxone •Penicilin ■Cefixime
2016
2017
2018
2019
2020
Figure 1. - Gonococcal Antimicrobial Resistance Surveillance Program (GRASP) in the United Kingdom 2016-2020 year
Ciprofloxacin Azithromycin Ceftriaxone Penicilin Cefixime
2000
2005
2010
2015
2019
Figure 2. — The Gonococcal Isolate Surveillance Project (GISP) in United States of America
70.00
40.00
30.00
Ciprofloxacin
Azithromycin
Penicilin
Ceftriaxone
Cefixime
0.00 H-X-1-*-1-*-1-*-1-*-1--1
2009 2010 2011 2012 2013 2014 2015 2016
Figure 3. - European Gonococcal Resistance Surveillance Program (Euro-GASP) 2009-2016
As can be seen from these graphs, different treatment policies between the United Kingdom, the United States, and the European Union have led to different trends in antibiotic resistance. For example, GRASP(UK) reports a decrease in penicillin resistance from 2007 to 2011, followed by an upward trend reaching 22.6% in 2014. Similarly, GISP(USA) also reports a steady upward trend in penicillin resistance, which has more than doubled in the last ten years (from 16% in 2004 to 3 8% in 2014). On the other hand, Euro-GASP (European Union) shows a stable level of penicillin resistance at 13-14% since 2004. As for ceftriaxone, all three reports had resistance rates close to 0%. GRASP(UK) and Euro-GASP(EU) detected a peak of cefixime resistance in 2011 and 2010, respectively, after which the resistance rate dropped significantly in both cases (from 11 to 1.4% for GRASP(UK) and 9-2% for Euro-GASP). The detection of
ciprofloxacin-resistant strains has increased in GRASP since 2012 (25 to 37.3% in 2014) and in GISP since 2009 (12 to 21% in 2014). On the other hand, Euro-GASP reports show a decrease in ciprofloxacin resistance from 63% in 2009 to 50% in 2014. Finally, resistance to azithromycin varies considerably among reports. GRASP shows azithromycin resistance rates below 2% since 2007, while GISP and Euro-GASP show an increase in resistant strains in 2014 (from 1 to 4% in GISP and from 5.4% to 7.9% in Euro-GASP).
Conclusion
Based on the red flags around the world, we have to assume that the superinfection of Neisseria gonorrhoeae is making scientists around the world wary. Following this trend, resistant strains will soon appear more and more often in other countries as well. There is a need for closer monitoring of strain prevalence at the regional level of each country and for global cohesion in reporting changes.
ОПАСНОСТЬ УСТОЙЧИВОСТИ NEISSERIA GONORRHOEAE К АНТИБИОТИКАМ ВО ВСЕМ МИРЕ
*Д.М. Амангельды, А.Т. Джумабеков, Б.А. Жумабекова
Казахстанский медицинский университет "ВШОЗ", Алматы, Казахстан
Аннотация
Гонорея - это инфекция, передающаяся половым путем, вызываемая бактерией Neisseria gonorrhoeae. По данным ВОЗ, число новых случаев заболеваний, передающихся половым путем, в 2020 году достигло 374 миллионов, четверть из которых были вызваны гонореей - 82,4 миллиона, что на 5,64% больше по сравнению с 2012 годом, когда было зарегистрировано 78 миллионов новых случаев.
Ключевые слова: neisseria gonorrhoeae, цефалоспорины, Проект по эпиднадзору за изолятами гонококка.
NEISSERIA GONORRHOEAE-ДЩ БYКIЛ ЭЛЕМДЕГ1 АНТИБИОТИКТЕРГЕ
Т0ЗШД1Л1К ЦАУШ
*Д.М. Амангелд1, А.Т. Жумабеков, Б.Э. Жумабекова
"^ДСЖМ" ^азакстан медициналык университету Алматы, ^азакстан
Тушндеме
Гонорея - Neisseria gonorrhoeae бактериясы тудыратын жынысты; жолмен берiлетiн инфекция. ДД¥ мэлiметтерi бойынша, жынысты; жолмен бершетш аурулардыц жаца жагдайлары 2020 жылы 374 миллионга жеттi, оньщ терттен бiр бeлiгi гонореядан 82,4 миллионга жетп, бул 2012 жылмен салыстырганда 5,64% - га ecri, бул кезде 78 миллион жаца жагдай тiркелдi.
Ty^h свздер: neisseria gonorrhoeae, цефалоспориндер, гонококк изоляттарын цадагалау жобасы.
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Conflict of interest. The author declares that there is no potential conflict of interest requiring disclosure in this article.
The contribution of the authors. The author contributed to the development of the concept, the execution and processing of the results, and the writing of the article. We declare that this material has not been previously published and is not under consideration by other publishers.
Financing. Absent. Information about the authors
Corresponding author. Daulet Amangeldy— Master's degree in the specialty «Public Health», LPP Kazakhstan's Medical University «KSPH», Almaty, Kazakhstan, E-mail: daulet93almaty@,gmail. com
Dzhumabekov Aueskhan Tulegenovich- MD, Professor, Kazakhstan Medical University "KSPH" LLP, Almaty, Kazakhstan, E-mail: jumabekov@mail.ru, ORCID https://orcid.org/0000-0002-3502-4411
Zhumabekova Botagoz Auyeskhankyzy — Article submitted: 12.02.2024
Accepted for publication:16.02.2024
