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19УДК: 616.992.282
OTOMYCOSIS: SOME ASPECTS OF EPIDEMIOLOGY AND CLINIC
RAKHMETOVA NURILA BERKENOVNA
Candidate of Biological Sciences, Associate Professor of the Department of Microbiology and Virology named after Sh.I. Sarbasova NJSC "Medical University Astana", Nur-Sultan, Kazakhstan. ORCID ID 0000-0003-4476-5470
AYAPBERGENOVA ZHULDYZ SERIKOVNA 3rd year student of the Faculty of Medicine NJSC "Astana Medical University", Nur-Sultan, Kazakhstan. ORCID ID 0000-0002-2371-6533 ABSTRACT
Mycoses are the top issue in clinical medicine and microbiology. The issue has an urgency due to an increase in the resistance of mycoses pathogens to antimycotic treatment, an increase in the number of immunocompromised individuals, in particular HIV-infected and oncological patients, and a deterioration of the environment worldwide. In addition, in connection with the changes occurring in the human body under the influence of the environmental factor, the range of pathogens of opportunistic mycoses, which were previously considered non-pathogenic, is expanding, the frequency of manifestations of rare and atypical forms of mycoses increases. In this regard, it becomes necessary to further research the problem of mycoses in order to study its new aspects.
Key words: mycosis, otomycosis, antimycotic drugs, opportunistic diseases, comorbidity
ОТОМИКОЗ: НЕКОТОРЫЕ АСПЕКТЫ ЭПИДЕМИОЛОГИИ И
КЛИНИКИ
РАХМЕТОВА НУРИЛА БЕРКЕНОВНА
кандидат биологических наук, доцент кафедры микробиологии и вирусологии имени Ш.И. Сарбасовой НАО «Медицинский университет Астана», Нур-Султан, Казахстан ORCID ID 0000-0003-4476-5470
АЯПБЕРГЕНОВА ЖУЛДЫЗ СЕРИКОВНА студентка 3 курса факультета «Медицина» НАО «Медицинский университет Астана», Нур-Султан, Казахстан.
ORCID ID 0000-0002-2371-6533
АННОТАЦИЯ
Микозы представляют актуальный вопрос клинической медицины и микробиологии. Серьезность проблемы обусловлена усилением резистентности возбудителей микозов к антимикотическим препаратам, увеличение количества иммунокомпрометированных лиц, в частности ВИЧ-инфицированных и онкологических пациентов, ухудшение экологической ситуации. Помимо этого, в связи с изменениями, происходящими в организме человека под влиянием экологического фактора, расширяется спектр возбудителей оппортунистических микозов, которые ранее считались непатогенными, увеличивается частота проявлений редких и атипичных форм микозов. В связи с этим возникает необходимость дальнейшего исследования проблемы микозов с целью изучения ее новых аспектов.
Ключевые слова: микоз, отомикоз, антимикотические препараты, оппортунистические заболевания, коморбидность
Mycoses, diseases caused by pathogenic and opportunistic fungi, are becoming increasingly important in modern medicine. This is the case due to several reasons, including an increase in the resistance of pathogens to antimycotic drugs, an increase in an amount of risk groups, and a deterioration in the environmental situation. In addition, due to intraspecific variability influenced by the environmental factors, the range of pathogens from among opportunistic fungi, which were previously considered non-pathogenic, is increasing, as well as the number of manifestations of rare and atypical forms of mycoses.
At the same time, the prevalence of various variants of mycotic lesions, their epidemiological features still have several issues that require thorough study, which can significantly affect the effectiveness of diagnosis and treatment.
One of the confirmations of the high worldwide scientific interest in the problem is the foundation of a specialized organization - Leading International Fungal Education (LIFE), with the aim of international coordination of mycoses research. Thus, in 2016, a group of Kazakh scientists conducted a study of the prevalence of severe and chronic mycoses in the Republic of Kazakhstan using the LIFE PROGRAM model - [1].
One of the interesting and urgent issues in the context of mycology is the otomycosis, particularly the epidemiology of the disease. Otomycosis is the second most common group of ENT pathologies. One of the confirmations of this trend is that today otomycosis has acquired a year-round character in comparison to the recent
past when the disease had a clear seasonality - [2-4]. This is due to the changes in human lifestyle such as development of mass tourism, travel to countries with a warm and humid climate, systematic visits to swimming pools.
The detection, treatment, and epidemiology of otomycosis are key issues of practical and scientific interest. This situation is associated with the specificity of the clinical picture of the disease and the peculiarities of its complications, with a certain complexity of differential diagnosis, and the appearance of atypical forms - [3, 5]. In particular, mycoses of the organ of hearing are more severe than other inflammations of the same location. The symptoms are often diagnosed at later stages of the disease, which can lead to the choice of an erroneous treatment strategy, the chronicity of the disease, the risk of developing visceral forms of mycosis as well as to an increase of the generalization risk of the pathological process. In addition, as a rule, the complaints of patients with various forms of otitis media are of a similar nature, which also complicates the differential diagnosis of the disease.
Chronic diseases of the auris media have not only medical, but also social significance, particularly because such an inflammation can result in hearing loss, and this defect is directly related to professional suitability and the quality of a person's social life. Along with this, the issue of the relationship between the development of otomycosis and working conditions remains open, in particular, work in rooms with an increased predisposition to the formation of household molds, frequent inhalation of spores, and their settling on intact and affected skin - [7, 8].
It is also worth considering that fungal lesions are more severe than other inflammatory processes of this localization. According to ICD-10 [9], abovementioned ENT diseases are the primary focus of intracranial infection, which is manifested by such pathologies as brain abscesses, extra- and subdural empyema, purulent meningitis. The occurrence of otogenic intracranial complications is facilitated by the anatomical and topographic features of the location of the auris media such as direct contact of the anatomical boundaries of the ENT organs with the dura mater. This relationship is also confirmed by bacteriological studies, during which they reveal the similarity of the microbiota of the ENT organs of the cerebrospinal fluid and intracranial abscesses - [6, 7].
In this way, in favor of the relevance of studying the issue both in general and for domestic science speak the specific clinical picture of otomycosis, the severity of its complications, the presence of a clinical and social factor in the disease
development, and its consequences, as well as the interest of foreign researchers in the problem of the clinic, treatment and epidemiology of the disease.
The aim of this work is to review the literature on the epidemiology and clinic of otomycosis in the Republic of Kazakhstan.
Materials and methods
The analysis of domestic and foreign scientific literature - articles on otomycosis for the period from 2011 to 2021, the study of open statistical data on the epidemiology and prevalence of otomycosis in the neighboring countries and Kazakhstan.
Results
Otomycosis is a fungal disease caused by the development of various opportunistic fungi on the walls of the external auditory canal. The causative agents of otomycosis in 61 % of cases are molds of the genus Asprgillus - A. niger, A. flavus, A. fumigatus, and in 28% of cases - yeast-like fungi of the genus Candida, in particular C. auris. The remaining 11 % of cases are attributed to fungi of the genera Penicillium, Rhizopus, and Mucor, separately or together with the Candida r. - [10-12].
The role of mucorous fungi in mycotic lesions of the ENT organs was noted in clinical study conducted by the Department of Otorhinolaryngology of KazNMU. In particular, in otomycosis, fungi of the genus Mucor occupy the third place, and in rhinomycosis - the second place after Aspergillus fungi -[10]. These data are generally confirmed by the results of Russian researchers who found that most often the causative agents of otomycosis are the Aspergillus fungi (57.9%), and fungi of the genus Candida are isolated in 36.36% of cases. The share of otomycosis in the structure of mycotic diseases of the ENT organs is about 42-50% - [13-15].
Depending on the localization, otomycosis is divided into fungal inflammation of the outer, middle ear and mycosis of the postoperative middle ear cavities. In the clinic, fungal otitis externa prevails - 67% of cases. Otitis media caused by micromycetes is observed in 17% of cases, and mycosis of the postoperative middle ear cavities - in 16% - [13, 14].
The main exogenous factor in the development of otomycosis is trauma to the epidermis of the walls of the ear canal. The most common causes of such an injury are manipulation with cotton swabs, micro and vacuum headphones, hearing aids, and water ingress. Endogenous factors usually have a concomitant character, i.e., they give the background of a weakened immune defense, for example somatic diseases, in particular diabetes mellitus, a general decrease in the body's resistance, metabolic
disorders, radiation, hormonal therapy, immunosuppressive or irrational antibiotic therapy - [16-19].
The pathological process in the outer ear begins subtle for the patient, and the complaints have a common character for different forms of otitis media: constant increasing itching in the ear, increased sensitivity of the ear canal and auricle, a feeling of congestion and noise in the ear. The fungal nature of the lesion can be suspected based on otoscopy data, otomicroscopy of the pathological discharge in the external auditory canal. The discharge looks like a «wet newspaper» of various colors depending on the color of the fungus mycelium. With mold otomycosis caused by fungi g. Penicillium, there is a liquid serous discharge and yellowish-white soft crusts throughout the external auditory canal. In case of a lesion caused by fungi g. Candida, the clinical picture is similar to weeping eczema, the process often extends to the auricle and behind the ear region - [20-23].
With a rather typical specificity of the otomycosis symptoms, microbiological studies should be of fundamental confirming importance in diagnosis. However, despite the mandatory character of the mycological examination for otitis externa, it has been established that in ordinary outpatient practice it is carried out in less than 10% of cases. The reliability of the results is often reduced by the fact of self-medication (before the diagnostic microbiological study). A diagnostic mistake cannot be ruled out when conducting a bacteriological study, thus, a negative answer in the clinical picture of mycotic lesions of the ear should raise doubts and require rechecking - [19, 22-23].
Based on the generalized data on the epidemiology of otomycosis, it was possible to determine that every year in the world 1 out of 250 people fall ill with acute otomycosis, the chronic form is observed in 3 - 5% of the world's population, i.e., about 200 - 350 million people. The acute form of otomycosis in 90% of cases result from comorbidity with bacterial otitis media, caused most often by pneumococci, staphylococci, Haemophilus influenzae. Comorbidity significantly complicates the diagnosis and treatment of otomycosis and involves complex drug therapy including medicines with both antibacterial and antimycotic activity. Directly pathogenic and opportunistic fungi result in otomycosis in 10% of cases.
The characteristic features of the otomycosis epidemiology are the mass prevalence, the universality of the occurrence among groups of patients different by gender, age, and region of residence. In addition, otomycosis, as a special case of
superficial mycosis, is generally found at the practice of doctors of various specialties and can also be directly polyclinic or nosocomial pathology - [24].
At the same time, it is important to note more specific data that otomycosis occurs in children on average 5% more often. Also, this pathology is more common in countries with a temperate climate: in the adult population from 10% to 37.8%, in children - from 15% to 26.3%, among other inflammatory diseases of the ear - [3, 15].
There is no direct relationship between social status, occupation, and the incidence of otomycosis. Several authors indicate the Candida albicans as a more frequent causative agent of otomycosis occurrence in women [25, 26].
The collected statistics provide only a generalized picture of the otomycosis epidemiology, which can be extrapolated to Kazakhstan only to a certain extent. It was not possible to find accurate statistical data on the prevalence of otomycosis in Kazakhstan in the public domain. This fact can be singled out as one of the issues that a researcher will have to face in this field. Compared to the closest neighbors of Kazakhstan, in particular Russia and Azerbaijan, it might be said that our country in this issue occupies an unfavorable position.
In Kazakhstan, the most adequate information on the issue of mycoses in general was obtained on the website of the Committee on Statistics of the Ministry of National Economy of the Republic of Kazakhstan, which provides statistical data on the incidence of dermatomycosis. So, the analysis for the period from 2015 to 2018 (the most recent published data, information for 2019 - 2021 has not been published at the moment) showed an unstable trend in the increase and decrease in the incidence:
• 2015 - 11,841 cases per year or 67.5 per 100 thousand people
• 2016 - 12103 cases per year or 68.0 per 100 thousand people
• 2017 - 10897 cases per year or 60.4 per 100 thousand people
• 2018 - 11655 cases per year or 63.8 per 100 thousand people. - [29]
At the same time, relying on the analysis of the domestic scientific literature, it
is noticeable that the attention of local researchers in the context of mycoses, is mainly attracted to contact dermatomycosis - trichophytosis, onychomycosis, microsporia and candidiasis, which are subject to mandatory registration. There is also no lack of the thorough case studies and statistical data on these pathologies.
Unfortunately, the above-mentioned information is not essential for achieving the goal of this work, since not representative and significant in the context of otomycosis.
The presented situation may equally indicate assumptions about:
- low scientific interest of domestic researchers in this issue, expressed in a small number of studies on epidemiology, diagnosis, treatment, or analysis of clinical cases of otomycosis
- closed access to these materials - articles, statistical data etc.
- absence of a unified (or disaggregated) statistical database.
Conclusion
In this way, the study of otomycosis in the contest of medical mycology has the potential for further research. Of particular interest are the issues of epidemiology, the possible relationship between the development of fungal infection of the ENT organs with social conditions, differential diagnosis, as well as targeted drug therapy for otomycosis.
It is observed the identification of certain changes in the characteristics of pathology in the epidemiology of otomycosis as the relatively higher prevalence of the disease among children, the disappearance of the seasonality factor.
As separate issues, one can single out such an aspect of the problem as maintaining statistical records of the incidence of otomycosis, as well as the accuracy of compliance with the requirements for microbiological laboratory confirmation of the diagnosis. These are the details, which with due attention, can allow to study presented issue more deeply, to identify important patterns, which eventually can have a positive influence on the effectiveness of disease treatment.
Up overall, it should be noted that today, despite the growing urgency of the issue of mycoses in medicine, in relation to the study of otomycosis and its epidemiology in the Kazakhstan research space interest in the problem remains low.
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УДК: 616-006.66
ТАРГЕТНАЯ ТЕРАПИЯ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ: РОЛЬ ПРОДИГИОЗИНА, ВЫДЕЛЕННОГО ИЗ SERRATIA MARCESCENS В МЕХАНИЗМАХ ВНУТРЕННЕГО И ВНЕШНЕГО ПУТЕЙ
АПОПТОЗА
РАХМЕТОВА НУРИЛА БЕРКЕНОВНА
кандидат биологических наук, доцент кафедры микробиологии и вирусологии имени Ш.И. Сарбасовой НАО «Медицинский университет Астана», Нур-Султан, Казахстан ORCID ID 0000-0003-4476-5470
БАЙБУСУНОВА АИДА ЖУМАТОВНА студентка 3 курса факультета «Медицина» НАО «Медицинский университет Астана», Нур-Султан, Казахстан.
ORCID ID 0000-0002-4460-0476 АННОТАЦИЯ
В настоящей работе обобщены известные данные о вторичном метаболите Serratia marcescens - продигиозине, а также выдвинута гипотеза о том, как именно пигмент индуцирует апоптоз. Рак молочной железы в структуре заболеваемости среди женщин в развитых и развивающихся странах занимает одно из первых мест, являясь эпителиальной формой рака с несколькими патогенетическими разновидностями. Одной из причин, обусловливающих резистентность опухолевых клеток к химиотерапии, является их способность восстанавливать (репарировать) вызванные химиопрепаратами повреждения ДНК. В этой связи, поиск терапии с менее выраженным цитотоксическим действием для организма является приоритетной задачей. Безусловный прорыв в современной медицине -создание «молекулярно-направленных» видов препаратов для избранного лечения. Открытием стал вторичный метаболит Serratia marcescens -продигиозин, оказывающий проапоптотическое действие на опухолевые клетки. На фоне эпидемиологии рака молочной железы, сдерживание опухолевого роста является не менее приоритетной задачей, наряду с полным выздоровлением.
Ключевые слова: таргетная терапия; рак молочной железы; продигиозин; Serratia marcescens; апоптоз
