THE PREVALENCE OF SERIOUS AND CHRONIC FUNGAL DISEASES IN THE RUSSIAN FEDERATION
Klimko N1, KozlovaY1, Khostelidi S1, Shadrivova O1, Borzova Y1, Burygina E1, Vasilieva N1 and Denning D2
1 I.Metchnikov North-Western State Medical University, St. Petersburg, Russia
2 The University of Manchester, UK in association with the LIFE program at
Abstract.The aim of this research is to estimate the prevalence of serious and chronic fungal diseases in the Russian Federation.According to the model proposed by LIFE (Leading International Fungal Education) communitywas determined the number of newly emerged diseases (tinea capitis, invasive aspergillosis, invasive candidiasis, cryptococcal meningitis, mucormycosis, Pneumocystis pneumonia) and chronic diseases (recurrent Candida vaginitis, recurrent oral and oesophageal candidiasis, chronic pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, severe asthma with fungal sensitization) in 2011 ( The data wasobtained from national studies and in the cases of their absence – from international studies. The total number ofpatients with serious and chronic fungal diseases was 2.7 million people in the Russian Federation in 2011. Most of these patients (2207093 persons) had superficial fungal infections: recurrent Candida vaginitis, recurrent oral and oesophageal candidiasis, tinea capitis.75995 patients had invasive mycosis: invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia. The total number of patients with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization was 406082.
Key words: fungal diseases, mycosis, Russian Federation
Introduction.
Over the past decades, fungal diseases have become a serious clinical problem. The number of fungal diseases is progressively increasing worldwide butmore epidemiologic studies are required. The prevalence of different variants of fungal infections remains unstudied. Exceptions are candidemia and cryptococcosis the incidence of which was analyzed in large population studies. National study of patients with candidemia was conducted in Denmark from 2004 to 2009 [1]. The results of multicenter study of cryptococcosis was published by Hajjeh RA, Conn LA, Stephens DS at al. in 1999.
For superficial mycosis is typical longtime relapsing course of disease. Invasive mycosis have severe clinical manifestations and high mortality rate. Many fungal infections arecharacterized by a rapid and aggressive course. Worldwide mortality from fungal infections is comparable to mortality from tuberculosis or malaria and is 1 350 000 patients per year [2,3]. Therefore, the LIFE (Leading international fungal education)organization has launched the initiative to calculate the preliminary epidemiological parameters for fungal diseases in many countries ( In our research we used the calculation models proposed by LIFE. The obtained data allows to estimate the prevalence of main chronic and severe fungal diseases in the Russian Federation.
The aim of this research is to estimate the prevalence of serious and chronic fungal diseases in the Russian Federation. Previouslysuch evaluation was not performed.
Materials and Methods.
According to the LIFE methodology, calculation was performed using the data received in 2011. The results of already published epidemiological studies of fungal infections in the Russian Federation were analyzed. If the official data was absent, we determined the size of specific groups with the risk of fungal infections development and then used published data of mycosis frequency in these groups of patients for estimating the national prevalence of mycosis. Statistics information about number and structure of Russian population was obtained from the Federal State Statistics Service (http:
The incidence of the scalp mycosis was assessed according to the data of the Ministry of Health [4].
Number of patients with chronic recurrent vulvovaginal candidiasis was calculated according to the international epidemiological studies data, which showed that this disease occurred in 5% of women in the population [5].
The number of patients with HIV/AIDS in the Russian Federation was evaluated according to the data of the Ministry of Health [6]. Different literature sources (Smith E, Orholm M. in 1990; Matee M.I., Scheutz F., Moshy J. in 2000) showed that oropharyngeal candidiasis was detected in 90% and esophageal candidiasis in 20% of HIV-infected patients.
According to the results of our previous studies, the incidence of candidemia and Candida peritonitis was 0.37 per 1000 persons hospitalized to in-patient department [7]. The total number of in-patients in hospitals for the year was obtained from the report about hospital-acquired infections of Federal Service on Consumers’ Rights Protection and Human Well-being Surveillance [8].
The prevalence of hematological diseases was evaluated according to the data of the Ministry of Health [9]. In patients with hematological diseases the risk of invasive aspergillosis (IA) development was calculated according to the data of the National Register of Patients with Invasive Aspergillosis created in St. Petersburg [10]. The information about number of organs and tissue transplantations made in 2011 was obtained from Russian Transplantation Society data [11]. Among patients who underwent hematopoietic stem cell transplantation (HSCT) the incidence of invasive mycosis was evaluated according to our earlier study results [12]. The total number of patients with IA was calculated according to the formula proposed by Denning D.W.:
10% of patients with acute myeloid leucosis + 0.5% of patients after kidney transplantation + 4% of patients after lung transplantation + 6% of patients after heart transplantation + 4% of patients underwent liver transplantation + 1.3% of patients admitted to hospital with chronic obstructive pulmonary disease = total number of patients with IA.
The incidence of mucormycosis in the general population was calculated using the data of the National Register created in St. Petersburg and the data of the Ministry of Health of the Russian Federationon acute myeloid leucosis prevalence [9].
The overall morbidity of tuberculosis was evaluated according to the information of the Ministry of Health [13]. The calculation of possible cases number of chronic pulmonary aspergillosis (CPA) was performed according to the formula proposed by Denning D.W. et al. [14]:
The annual number of cases of tuberculosis of lungs with the presence of cavities (≈ 12% of the total number) the risk of CPA development (22%) + the number of emerged cases of tuberculosis without cavities (≈ 88% of the total incidence) risk of CPA in this patients (2%) = possible cases of CPA.
The number of patients with asthma was obtained from the data of the Russian Respiratory Society [15]. The estimated number of patients with allergic bronchopulmonary aspergillosis (ABPA) was calculated by another formula proposed by Denning D.W. et al. [16]:
2.5% of patients with asthma + 155 of adult patients with cystic fibrosis = estimated patients with ABPA.
To assess patients with severe asthma with fungal sensitization was considered that 10% of patients with asthma have severe course of disease and 33% of them have fungal sensitization [17].
The information about cystic fibrosis (CF) incidence was obtained from the Russian Register of Patients with Cystic Fibrosis [18]. According to the data of Medical Genetic Research Center of Russian Academy of Science among patients with CF 21% were adults [19].
The results of research performed in St.Petersburgwas usedto calculate the incidence of cryptococcal meningitis. In 2011 cryptococcal meningitis occurred in 0.44 % ofpatients with HIV [20]. The number of Pneumocystis pneumonia cases was calculated on the base of the LIFE data according to which Pneumocystis pneumonia develops in 60% of HIV-infected patients who receive antiretroviral therapy.
Results and Discussion.
In 2011 the population of the Russian Federation was 142.9 million, 85% of which were adults and 15% werechildren younger than 14 years. Among adults 54% were women. In table 1 is showed the prevalence of different fungal diseases and its incidence per 100000 inhabitants.
Fungal diseases of the scalp
According to the data obtained from the Ministry of Health of the Russian Federation the total number of patients with tinea capitis (caused by Microsporum canis orTrihophyton spp.) was 60366 persons, 47092 of which were children.The prevalence of tinea capitis caused by Microsporum caniswas40.8 per 100000 persons and 213.1 per 100000 children. Tinea capitis caused by Trihophyton spp.was less frequent – 1.8 per 100000 persons and 6.9 per 100000 children. These results exceeded the average levels in Europe. For example, in Greece the overall incidence of tinea capitis was 6.06 per 100000 people [21], in Denmark – 3.3 per 100000 [22]. According to the data of LIFE experts the highest incidence of these superficial mycosis was in Vietnam– 457 per 100000 people [23].
Mucosal candidiasis
Chronic recurrent vulvovaginal candidiasis is characterized by frequent relapses (at least 4 per year) and is the most common recurrent fungal disease in Russia. According to our estimations 2072679 Russian women suffer from chronic recurrent vulvovaginal candidiasis which is 2900 per 100000 people. The similar data was obtained in Europe (in Hungary – 2193 per 100000)[24] and in other countries (in Iraq – 2664 per 100 000)[25]. In Ukraine the prevalence of recurrent vulvovaginal candidiasis is higher – 3923 per 100000 people [26].
In 2011 inRussia the number of patients with first diagnosed HIV infection was 67317 (47.1 per 100000 people) [9]. Hence, the number of HIV-infected patients with oropharyngeal candidiasis amounted 60585 persons (42.4 per 100000 people). The estimated number of HIV-infected patients with Candida esophagitis was 13463 persons (9.42 per 100000). International epidemiological observations also are focused on the study of Candida esophagitis only in the group of HIV-infected patients. According to the data of LIFE experts the frequency of this fungal disease in Hungarywas 1.56 per 100000 people, in the UK and Denmark – 0.1 per 100000 [22, 27, 24]. Currently, the determination of esophageal candidiasis incidence in patients without HIV infection is a subject of one of our researches.
Invasive candidiasis
In 2011, 32 million patients were treatedin the inpatient departmentsof the Russian Federation. The total number of patients with invasive candidiasis was 11840 per year. Thus, the frequency of invasive candidiasis in the population was estimated 8.29 per 100000 people. These values corresponds to the average levels in Europe. In European countries this parameter varies from 5.0 to 11.4 per 100000 people. However, the international studies showed that 50% of patients in the ICU with candidemia had Candida peritonitis [28]. According to the results of our research candidemia was noted more often (82%) than Candida peritonitis (18.4%) [7].
Pulmonary aspergillosis
It is known that hematologic diseases are one of the major risk factor for invasive aspergillosis (IA) development. According to our register, 88% of patients with IA have hematologic diseases 30% of which is acute myeloid leucosis (AML). This data correlates with theresults of European studies. The incidence of AML in patients with IA in Italy is 36% [29], in France – 35% [30]. According to the European average values, the risk of IA in these patients is 10%. Thus, in Russia every year there are 160 new cases of IA in patients with AML. According to the formula proposed by Denning D.W. the same number of IA cases develops in patients with other hematologic malignancies.
Annuallyabout 200 hematopoietic stem cell transplantations are carried out in theRussian Federation [11]. According to the results of the studies made in St. Petersburg, the incidence of invasive mycosis in HSTC recipients was 19.1% and in recipients of allogeneic HSCT – 23.2% [12]. 82.3% of these mycoses were caused by fungi of the genus Aspergillus spp. Thus, in Russiathe incidence of invasive aspergillosis in HSCT recipients varied from 16 to 20%. For calculation was used the rate 20%, so in these patients there were 40 cases of IA.
Organ and tissue transplantation and the related glucocorticoid therapy are also the risk factors for IA. Most often IA develops in lung transplant recipients. The results of international studies show that the incidence of IA after organ transplantations varies from 0.3 to 14% [31, 32]. According to the data of the Federal Scientific Center of Transplantation and Artificial Organs named after Academician V.I. Shumakov in Russia in 2011 was performed 975 kidney transplantations, 204 liver transplantations and 106 heart transplantations [33]. For determining the risk of IA we used the European average values which believed to be 0.5% of patients after kidney transplantation, 4% - after lung transplantation, 6% - after heart transplantation, 4% - after liver transplantation. It amounted in total 19 cases of IA in 2011. Summing up all the parameters, 385 cases of invasive aspergillosis had occured in hematological patients and recipients of solid organs transplants.
In the Russian Federation in 2011 was hospitalized 219322 in-patients with chronic obstructive pulmonary disease (COPD). According to Denning D.W. the risk of IA development in these patients was 1.3%. Thus IA had occurred in 2853 with COPD. Using the above mentioned formula was calculated the total number of newly emerged IA in the Russian Federationwhich amounted 3238 patients (2.27 cases per 100000 people). According to the data of LIFE experts the similar results of IA prevalence were obtained in European countries (in Greece – 3.27 per 100000, inHungary – 1.54 per 100000) as well as in Iraq (2.62 per 100 000) [21, 24, 25].
Chronic pulmonary aspergillosis (CPA) occurs in patients with chronic pulmonary diseases (tuberculosis, sarcoidosis, chronic obstructive pulmonary disease, cystic fibrosis). Overall incidence of tuberculosis in Russia in 2011 was 104320 cases (68.1 per 100 000), which included 94297 cases of pulmonary tuberculosis (66.0 per 100 000). Fibrous-cavernouslung tuberculosis was diagnosed in 1901 patients (1.33 per 100000 population). Among the resident population of Russia 10.3% of patients with tuberculosis were HIV-positive. The incidence rate of tuberculosis in association with HIV infection in 2009 was 4.4 per 100000 population, in 2011 – 5.6 per 100000. The possible cases of chronic pulmonary aspergillosis were calculated in accordance of the formula proposed by Denning D.W. et al. During 5-year period 13078 cases of CPA on the background of tuberculosis have occurred according this calculation. The total number of patients with CPA was 52311 (126 per 100000 population). This data was consistent with the results in Ukraine where the frequency of CPA was 109 per 100000 population. In other countries this parameter was much lower: in the UK – 8.1/100 000, inGreece – 3.48/100000, in Denmark – 3.05/100 000 [27, 21, 22].
Mucormycosis.
According to the data of the register of patients with mucormycosis in St. Petersburg in 2011, was calculated the incidence of mucormycosis in patients with acute myeloid leucosis (AML) which was 3.6%. In 2011 inthe Russian Federation overall was registered 1599 patients with AML. In accordance to our calculations,in 58 hematologic patients the disease was complicated by mucormycosis. On the basis of our study results, AML was a risk factor for mucormycosis only in 25% of cases. Thus, the total number of patients with mucormycosis was 232 people (0.16/100 000). The calculated incidence of mucormycosis in Russian Federation corresponded to the values in European countries. The frequency of mucormycosis in Greece was 0.12/100 000, inHungary – 0.1/100 000 population [21, 24].
Allergic bronchopulmonary disease
Epidemiological prevalence of asthma in Russia, as in other countries, far exceeds the official medical statistics data. The experts of the Russian Respiratory Society estimated that the number of patients with asthma in theRussian Federation is about 7 million people. Using the formula proposed by Denning D.W. et al [16, 17] was calculated the estimated number of patients with allergic bronchopulmonary disease (ABPA), which was 175082 patients, and number of patients with severe asthma and fungal sensitization (SAFS), which was 231000 people. The total number of patients with ABPA and SAFS was 406082 people. The incidence of ABPA and SAFS in the Russian Federation corresponded the parameters in Denmark (ABPA – 125/100 000; SAFS – 163/100 000). According to the data of LIFE experts the highest frequency of ABPA was in UK (287/100 000) and the lowest was in Iraq (16/100 000) [22, 27. 25].
Pneumocystis pneumonia and cryptococcal meningitis.
Pneumocystis pneumonia (PCP) and cryptococcal meningitis are among the major opportunistic infections in patients with HIV. In the Russian Federation the incidence of PCP was 5.65 cases per 100000 people or 8078 cases per year. High incidence of PCP also was marked in Ukraine – 13.5/100 000 [26]. In other countries this parameter was lower: in the UK – 0.94/100000, in Greece – 0.52/100 000, inHungary – 0.05/100 000 people [27, 21, 24].
The overall incidence of cryptococcal meningoencephalitis in theRussian Federation was 296 cases per year (0.21/100 000), which corresponded to the data in Ukraine (0.22/100 000) [26]. In the UK the frequency of cryptococcal meningoencephalitis was 0.16 per 100000 population [27]. In other European countries the incidence of this opportunistic infection was lower. For example, in Greece were detected less than five cases per year, in Denmark – two cases per year [21, 22].
In Russia the high incidence of Pneumocystis pneumonia and cryptococcal meningitis was certainly related to a large number of HIV patients in the country. Despite the antiretroviral therapy, the number of patients detected in the later stages of the disease with severe secondary lesions continues to grow.
Our study showed that mycoses are common diseases in Russian Federation. However, in our work, we haven’t evaluated all fungal diseases because we wanted to save a single model of the LIFE research and to have opportunity to compare the results with those of other countries. For example, in this study we haven’t included mycosisof the smooth skin, mycosis of the feet and hands, onychomycosis, chronic candidiasis of the skin and mucous, and some others.
We compile and constantly update the register of patients with severe invasive fungal diseases but we don’t have our own data of the chronic fungal diseases prevalence. In this work we used the results of international researches. Therefore, one of the main tasks in the study of fungal diseases in the Russian Federation is registration not only the newly diagnosed cases of invasive fungal infections but also chronic fungal infections (ABPA, SAFS, CPA, chronic recurrent vulvovaginal candidiasis).
Further study of the mycosis epidemiology is especially important because the results of it are the basis for preventive measures and treatment optimization of fungal diseases throughout the world.
Conclusions.
- Mycosis are common diseases in theRussian Federation. In 2011, according to the estimation, there were 2.7 million patients with severe and chronic fungal disease.
- Chronic superficial mycoses (recurrent vulvovaginal candidiasis, recurrent oral and esophageal candidiasis, tenia capitis) had occurred in 2207093 people.
- Invasive fungal diseases (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis, Pneumocystis pneumonia) had occurred in 75995 patients.
- The total number of patients with ABPA and SAFS was 406082.
- In the Russian Federation is required registration of severe and chronic fungal diseases as well as conducting further epidemiological studies of mycoses.
Table 1.
Fungal Diseases in Russian Federation
Fungal Diseases / Rate/100K / Total BurdenNewly emerged diseases / Invasive aspergillosis / 2,27 / 3238
Invasive candidiasis: / 11840
Cryptococcal meningitis / 0,21 / 296
Mucormycosis / 0,16 / 232
Pneumocystis pneumonia / 5,65 / 8 078
Tinea capitis (caused by Microsporum canis) / 40,8 / 57 871
Tinea capitis (caused by Trihophyton spp.) / 1,8 / 2 495
84 050
Chronic diseases / Chronic recurrent Candida vulvovaginitis / 2900 / 2072 679
Recurrent oral candidiasis / 42,4 / 60 585
Recurrent oesophageal candidiasis / 9,42 / 13 463
Chronic pulmonary aspergillosis / 126,19 / 52 311
Allergic bronchopulmonary aspergillosis / 122,52 / 175 082
Asthma with fungal sensitization / 161,65 / 231 000
2605 120
Total burden estimated / 2689 170
References.