Warning: fopen(/home/virtual/epih/journal/upload/ip_log/ip_log_2025-01.txt): failed to open stream: Permission denied in /home/virtual/lib/view_data.php on line 95 Warning: fwrite() expects parameter 1 to be resource, boolean given in /home/virtual/lib/view_data.php on line 96 Oral colonization by Candida species and associated factors in HIV-infected patients in Ahvaz, southwest Iran
Skip Navigation
Skip to contents

Epidemiol Health : Epidemiology and Health

OPEN ACCESS
SEARCH
Search
Advanced Search
mobile menu button

Articles

Page Path
HOME > Epidemiol Health > Volume 42; 2020 > Article
Original Article
 Oral colonization by Candida species and associated factors in HIV-infected patients in Ahvaz, southwest Iran
Elham Aboualigalehdari1orcid, Maryam Tahmasebi Birgani2orcid, Mahnaz Fatahinia1,3orcid, Mehran Hosseinzadeh4orcid
Epidemiol Health 2020;42:e2020033.
DOI: https://doi.org/10.4178/epih.e2020033
Published online: May 24, 2020

1Department of Medical Mycology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3Infectious and Tropical Diseases Research Center, Health Research Institute, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Correspondence: Mahnaz Fatahinia Department of Medical Mycology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 61357-15794, Iran E-mail: fatahinia@yahoo.com
• Received: March 10, 2020   • Accepted: May 24, 2020

©2020, Korean Society of Epidemiology

This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

prev next
  • 15,771 Views
  • 175 Download
  • 14 Web of Science
  • 12 Crossref
  • 15 Scopus
Full Article

Download PDF Download PDF

  • OBJECTIVES
    Oropharyngeal candidiasis is one of the most common opportunistic fungal infections among human immunodeficiency virus (HIV)-infected individuals. The most common cause is Candida albicans, followed by non-albicans Candida. This study aimed to identify colonized Candida species in HIV-infected patients from Ahvaz, Iran. Additionally, the relationships between immunity-related factors, lifestyle, and colonization of Candida spp. were studied.
  • METHODS
    Oral swabs were taken from 201 HIV-positive patients referred for consultations at the Behavioral Modification Center. Oral Candida colonization was detected using culture-based and molecular assays. Data were assessed by descriptive statistics and analyzed to investigate the correlation between Candida colonization and various factors, including the CD4+ cell count and viral load.
  • RESULTS
    It was found that 43.8% of patients were positive for Candida. The most common species was C. albicans (48.0%), followed by non-albicans Candida isolates, including C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis, C. guilliermondii, C. kefyr, and C. krusei. Colonization of Candida spp. in patients was associated with a CD4 count ≤200 cells/mm3 (odds ratio [OR], 4.62; p<0.05), history of shared injections (OR, 6.96; p<0.001), and sex (OR, 3.59; p<0.05).
  • CONCLUSIONS
    The results of this study showed that C. albicans was the dominant pathogen. The risk factors for colonization of Candida spp. were a CD4 count ≤ 200/mm3 , a history of shared injections, and sex. Other factors with potential relationships include viral load, age, and opportunistic infections, but further investigations are needed.
  • Keywords: Candidiasis, Oral, Species, Colonization, Human immunodeficiency virus, Iran
Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection that affects the oral mucosa. Although Candida albicans is the most common causative agent of OPC, non-albicans Candida species have also been reported to be responsible for OPC, which is mostly observed in patients undergoing chemotherapy and in transplant recipients. OPC is also one of the most frequent infections in human immunodeficiency virus (HIV)-infected patients, as it has been observed in more than 90% of HIV patients. Remarkably, OPC has been detected in early stages of HIV before treatment, as well as in advanced stages of acquired immune deficiency syndrome (AIDS) [1,2].
OPC is mostly diagnosed through its clinical manifestations, which include a burning sensation, buccal pain, taste changes, and pseudomembranous, erythematous, and angular cheilitis [3,4]. To treat OPC, it is necessary to identify the causative species because a majority of infections contain mixed Candida spp. Both C. albicans and non-albicans Candida spp. may be affected by acquired and intrinsic antifungal resistance, which could influence the management of the disease and contribute to the spread of candidiasis to esophageal tissue, malnutrition, and interference with drug absorption. Consequently, the identification of the causative species is necessary and the diagnosis should be made using both culture and molecular methods [5-7]. Oral candidiasis is a prognostic indicator in HIV patients, as well as a predisposing factor for fungal infections such as candidemia and esophageal candidiasis. Dental prostheses, smoking, and hormonal, nutritional, immunological, and salivary changes predispose HIV patients to oral candidiasis [3,8,9].
The current study aimed to evaluate the colonization of Candida spp. in HIV-positive patients, to determine the distribution of Candida spp., and to identify the relationships of Candida spp. colonization with a CD4 count ≤ 200 cells/mm3, viral load, history of shared injections, sex, age, intravenous drug use, underlying disease (hepatitis C, tuberculosis [TB], hepatitis B, Pneumocystis carinii pneumonia [PCP]), having a safe and secure sexual relationship, the use of antiretroviral medication, and the use of prophylactic medication (for PCP and TB).
Study subjects
HIV-infected outpatients aged 6-81 years (n=201) were referred for consultations to the Behavioral Disease Center of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran from December 2018 to April 2019 for viral load and CD4+ T-cell count measurements. HIV positivity was the sole inclusion and exclusion criterion for sampling.
The subjects were interviewed about their medical history and information was extracted from their medical records on sex, age, intravenous drug use, underlying diseases (hepatitis C, TB, hepatitis B, and PCP), whether they had a safe and secure sexual relationship, antiretroviral medication use, and history of using prophylaxis drugs (for PCP and TB).
Initial identification of yeasts
Samples from the oral cavity of HIV-positive participants were collected with a sterile cotton swab, seeded onto CHROMagar Candida plates (CHROMagar, Pioneer, Paris, France), and incubated aerobically at 37°C for 48-72 hours. Colonies with similar morphology and color on CHROMagar plates were counted and the result was expressed in colony-forming units per milliliter (CFU/mL) after 48-72 hours of incubation at 37°C on CHROMagar plates. Patients with ≥ 10 CFU/mL were considered to be colonized [10].
Patients who were asymptomatic for oral candidiasis with ≥ 10 CFU/mL were defined as having been colonized by Candida, but asymptomatic patients with < 10 CFU/mL were considered noncolonized. The next step was the purification of isolates, which were cultured on Sabouraud Dextrose agar (Lifoilchem, Roseto degli Abruzzi, Italy). The initial identification of isolates to the species level was performed by classical and standard methods such as germ tube test, growth at 45°C, and production of chlamydoconidia and hyphae on corn meal agar (Lifoilchem) with Tween 80.
Molecular identification of yeasts
Firstly, the genomic DNA was directly extracted from purified colonies in sterile distilled water by boiling [6,11]. Polymerase chain reaction (PCR) was performed by sequencing an internal transcribed spacer (ITS1-5.8S rDNA-ITS2) region and using universal fungal primers (Table 1). The PCR amplification conditions consisted of an initial denaturation at 95°C for 5 minutes, followed by 35 cycles at 95°C for 35 seconds, 58°C for 30 seconds, 72°C for 1 minute, and a final extension at 72°C for 10 minutes. All PCR tests had a negative (no template) control and a positive (sequence template) control. Finally, to determine the species, the positive specimens were identified by restriction fragment length polymorphisms [12]. Each of the amplified PCR products was digested using MspI (Hpa III; Thermo Fisher Scientific, Waltham, MA, USA) restriction enzymes and incubated at 37°C for 1-16 hours. The digested products were run on 2% agarose gel and stained with 0.5 μg/mL ethidium bromide. Since the MspI enzyme is not able to differentiate C. albicans from C. dubliniensis or C. albicans from C. dubliniensis, isolates suspected to be C. albicans or C. dubliniensis were distinguished by duplex PCR using primers targeting sequences in the ITS-1 and ITS-2 regions of the rDNA (Table 1) [13]. The PCR reaction started at 95°C for 5 minutes, followed by 35 cycles of 95°C for 30 seconds, 60°C for 45 seconds, 72°C for 30 seconds, and a final extension at 72°C for 5 minutes.
Statistical analysis
Data were assessed using descriptive statistics (frequency, percentage, mean, standard deviation). Associations between categorical variables were analyzed using the chi-square test or Fisher exact test. Variables with p-value< 0.2 in the univariate analysis were included in the multiple logistic regression analysis model. Multicollinearity was checked, and all variables had a variance inflation factor well below 5. The Hosmer-Lemeshow test was used to evaluate the goodness-of-fit for multiple logistic regression. The Kolmogorov-Smirnov test was used to assess the normality of the distribution of continuous variables, and variables that did not have a normal distribution were compared using the Mann–Whitney test. All analyses were performed using R version 3.5.2 (https://cran.r-project.org/bin/windows/base/old/3.5.2/) and SPSS version 22 (IBM Corp., Armonk, NY, USA). A p-value< 0.05 was set as the threshold for statistical significance.
Ethics statement
This cross-sectional study received ethical approval from the research deputy of Jundishapur University of Medical Sciences, Ahvaz, Iran (code #1397/893).
The current study analyzed 201 HIV-infected patients, including 115 male and 86 female patients aged 6-81 years. Patients’ sociodemographic characteristics are summarized in Table 2. The colonized (≥ 10 CFU/mL) and non-colonized groups (< 10 CFU/mL) accounted for 43.8% and 56.2% of the sample, respectively. No statistically significant differences were found between the 2 groups in terms of TB prophylaxis, PCP, antiretroviral therapy, blood transfusion, mother-to-child transmission, addiction history, homosexuality, education, occupational exposure, and hepatitis B or hepatitis C virus infection, although people with male sex, a history of drug injection, TB, a history of shared injections, and a CD4 count ≤ 200/mm3 were more likely to be colonized (p<0.05).
The age distribution and Candida load in the colonized group were significantly different from those of the non-colonized group, although the viral load was similar in the 2 groups (Table 3). The p-value of the Hosmer–Lemeshow test was 0.387, indicating a goodness-of-fit data. The factors associated with colonization were subjected to multiple logistic regression analysis. Sex (odds ratio [OR], 3.59; 95% confidence interval [CI], 1.23 to 10.46; p<0.05), a history of shared injections (OR, 6.96; 95% CI, 2.46 to 19.65; p<0.001), and CD4 count (OR, 4.62; 95% CI, 1.43 to 14.90; p<0.05) showed significant differences between the colonized and noncolonized groups (Table 4).
From the study population, 127 strains of Candida were isolated in 88 colonized patients. C. albicans was the most common strain isolated, accounting for 48.0% of isolates (61/127), while non-albicans Candida strains were found in the remaining 52.0% of isolates (66/127). The most common species among the non-albicans Candida isolates were C. dubliniensis and C. glabrata, with prevalence rates of 22.8% (n= 29) and 14.1% (n= 18), respectively. The distribution of the isolated species is shown in Table 5.
In 32 patients (36.4%), more than 1 Candida spp. was isolated. The cocolonization distribution is shown in Table 6.
The aim of this study was to obtain epidemiological data on the colonization of different Candida species in HIV-infected patients in Ahvaz, Iran. HIV patients have a high incidence of Candida colonization and are more susceptible to OPC [14,15].
In our study, the rate of Candida colonization in patients with HIV infection was 43.8%, which is similar to those reported in other studies conducted in China (49.5%), Brazil (50.4%), and Taiwan (51.4%) [3,16]. However, a very broad range of Candida colonization rates among HIV-infected patients (11-96%) has been reported in other studies [10]. The prevalence of Candida spp. colonization may vary based on factors such as sampling methods, diagnostic techniques, and geographical and ethnic differences [10,17]. Colonization ranges of 16-56% have been reported using swab mouth sampling [10].
In a review study by Patil et al. [18] in 2018, the most common strain isolated from HIV patients with OPC was C. albicans (37.2-95.2%), followed by C. glabrata (0.99-23.00%). In our study, C. albicans was the most common oral yeast in HIV-infected patients with a frequency of 69.3% [19-22]. On one hand, C. dubliniensis has been reported to be the second most common and dominant non-albicans Candida spp. in some studies, followed by C. glabrata [2,22-24]; on the other hand, other studies have identified C. glabrata as the most common non-albicans Candida spp. [19,25, 26]. In recent years, we have witnessed an increase in C. dubliniensis as the most prevalent species after C. albicans even in healthy individuals without HIV [27,28]. The absence of molecular techniques in the past when species were identified using traditional methods may explain this phenomenon, because C. dubliniensis is similar to C. albicans and has wrongly been reported as C. albicans.
The increase in C. dubliniensis among HIV patients is concerning because exposure to fluconazole may aggravate fungal adhesion to the oral epithelium. Since HIV-infected patients receive fluconazole to prevent this adhesion [27,29], there is a risk of increasing oropharyngeal candidiasis with C. dubliniensis and other non-albicans Candida spp., as well as resistance to fluconazole, leading to prolonged treatment and higher morbidity and mortality rates due to OPC [5,30-32].
In our study of 88 colonized patients, 59 (67.0%) had only 1 type of Candida spp. and the remaining patients (32.9%) had a combination of 2 or 3 yeast species. It can be clinically challenging when susceptible and less susceptible or resistant species to an antifungal medication coexist (i.e., coinfection), such as C. glabrata and C. krusei, which are less susceptible to fluconazole and voriconazole and were present in 14.1% and 0.7% of Candida carriers in this study, respectively. In contrast, C. parapsilosis and C. tropicalis (3.9% and 6.2% of Candida carriers in this study, respectively) have a similar sensitivity to that of C. albicans [18].
These observations underscore the importance of species assessment using Candida CHROMagar medium, which is a low-cost and convenient method of species identification, especially for samples involving more than 1 species [33]. The factors potentially related to oral colonization by Candida spp. in HIV-infected individuals were evaluated in this study. Through multiple logistic regression analysis, one of the risk factors for Candida colonization was identified as a CD4 count ≤ 200/mm3 (OR, 4.62; 95% CI, 1.43 to 14.90; p<0.05). Therefore, in this study, the oral cavity of HIV-infected individuals with a low CD4 count was approximately 5 times more likely to be colonized by Candida spp., implying that the environment in the oral cavity of these patients was likely 5 times more immunosuppressive. Therefore, Candida colonization could be considered as a proxy marker of immunosuppression based on the findings of this study, with potential for use in circumstances where it is not possible to measure CD4 counts. Our results are consistent with those of other studies in this respect [32,34-38]. According to the observations of this study, shared injections increased the risk of Candida colonization in HIV patients by approximately 7-fold compared to other HIV patients (OR, 6.96; 95% CI, 2.46 to 19.65; p<0.001), which aligns with the findings of other studies [32,39,40]. Furthermore, the colonization rate of males was approximately 4 times higher than that of females (OR, 3.59; 95% CI, 1.23 to 10.46; p<0.05), which may reflect the higher prevalence of HIV in males [41,42]. Other conditions that may occur, depending on the status of the patient’s immune system, include opportunistic infections such as TB. An analysis using the chi-square test showed a significant relationship between TB and oral Candida colonization (p<0.05). Consistent with other studies [43], oral candidiasis can be a useful clinical tool for screening HIV patients for TB, and we recommend that when an HIV patient with oral candidiasis is referred to a clinic, he or she should be checked for TB and receive prophylaxis for TB [44]. Viral load is another host-related factor, but despite experiments indicating that HIV load reduces immunity on mucosal surfaces and increases the secretion of acid protease from C. albicans, the Mann-Whitney test showed that our results were not statistically significant; this finding is in agreement with some studies, but not with others [10,45,46]. A possible explanation for this phenomenon might be that insufficient information was available about patients’ viral load and that the test was performed among existing patients; therefore, the insufficient data in this study might not have had sufficient statistical power to show these differences.
Our results showed the rate of Candida colonization and Candida spp. abundance and diversity in HIV-infected patients in Ahvaz, Iran. C. albicans was dominant on the oral mucosal surfaces of these patients, and C. dubliniensis was the most common yeast among non-albicansCandida spp. A CD4 count of ≤200/mm3 had a strong association with Candida colonization, confirming that the cellular immune response plays a vital role in protecting against OPC and that an impaired immune response could be a risk factor. A number of factors, such as viral load and opportunistic infections, require further investigation in larger populations of patients. Therefore, there is a need for further research on this issue in Iran to better clarify these findings.

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare for this study.

FUNDING

This study was supported by Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (No. OG-9743).

AUTHOR CONTRIBUTIONS

Conceptualization: MF. Data curation: EA, MH. Formal analysis: EA. Funding acquisition: MF. Methodology: EA, MTB, MF. Project administration: MF. Writing – original draft: EA. Writing – review & editing: MTB, MF, MH.

None.
Table 1.
List of primers used in this study
Primers Reference
ITS1 5´-TCC-GTA-GGT-GAA-CCTGCG-G-3´ [9]
ITS4 5´-TCC-TCC-GCT-TAT-TGA-TAT-GC-3´
CALF 5´-TGGTAAGGCGGGATCGCTT-3´ [13]
CALR 5´-GGTCAAAGTTTGAAGATATAC-3´
CDUF 5´-AA ACTTGTCACGAGATTATTTTT-3´ [13]
CDUR 5´-AAA GTTTGAAGAATAAAATGGC-3
Table 2.
The frequency of socio-demographic characteristics of the study subjects
Variables Colonized (n=88) Non-colonized (n=113) p-value1
Sex
 Male 63 (54.8) 52 (45.2) <0.001
 Female 25 (29.1) 61 (70.9)
Drug injection
 True 47 (57.3) 35 (42.7) 0.001
 False 41 (34.5) 78 (65.5)
TB
 Yes 15 (68.2) 7 (31.8) 0.015
 No 73 (40.8) 106 (59.2)
TB prophylaxis
 Yes 6 (30.0) 14 (70.0) 0.191
 No 82 (45.3) 99 (54.7)
PCP
 Positive 12 (63.2) 7 (36.8) 0.074
 Negative 76 (41.8) 106 (58.2)
ARV
 Yes 85 (42.9) 113 (57.1) 0.082
 No 3 (100) 0 (0.0)
Blood transfusion
 True 1 (100) 0 (0.0) 0.438
 False 87 (43.5) 113 (56.5)
Mother-to-child transmission
 True 3 (60.0) 2 (40.0) 0.655
 False 85 (43.4) 111 (56.6)
Addiction history
 Yes 51 (49.5) 52 (50.5) 0.093
 No 37 (37.8) 61 (62.2)
Education
 No education 11 (57.9) 8 (42.1) 0.1932
 Elementary education 75 (41.7) 105 (58.2)
 Higher education 2 (100) 0 (0.0)
Homosexuality
 True 5 (71.4) 2 (28.6) 0.244
 False 83 (42.8) 111 (57.2)
HCV Ag
 Positive 31 (50.0) 31 (50.0) 0.235
 Negative 57 (41.0) 82 (59.0)
HBV Ag
 Positive 4 (50.0) 4 (50.0) 0.732
 Negative 84 (43.5) 109 (56.5)
Occupational exposure
 True 1 (50.0) 1 (50.0) 1.000
 False 87 (43.7) 112 (56.3)
Shared injection history
 Yes 37 (72.5) 14 (27.5) <0.001
 No 51 (34.0) 99 (66.0)
CD4 count (cells/mm3)
 ≤200 20 (80.0) 5 (20.0) <0.001
 >200 68 (38.6) 108 (61.4)

Values are presented as number (%).

TB, tuberculosis; PCP, Pneumocystis carinii pneumonia; ARV, antiretroviral; HCV, hepatitis C virus; HBV, hepatitis B virus; Ag, antigen.

1 Chi-square test or Fisher exact test.

2 Tests were performed after pooling the last 2 groups (elementary education, higher education) in order to eliminate small expected frequencies.

Table 3.
Characteristics of the study population
Variables Colonized
 Non-colonized
 p-value1
n Mean±SD n Mean±SD
Age 88 40.61±12.55 113 37.15±8.18 0.005
Viral load 36 802,637.71±2,544,107.27 27 3,150,032.340±11,343,051.38 0.064
Candida load 88 5,787.51±23,256.64 58 3.50±2.12 <0.001

SD, standard deviation.

1 Mann-Whitney test.

Table 4.
Prevalence rates of oral colonization by Candida species
Variables OR (95% CI) p-value
Sex (ref: female) 3.59 (1.23, 10.46) 0.019
Age 1.01 (0.98, 1.04) 0.376
Drug injection (ref: false) 0.78 (0.22, 2.68) 0.697
TB (ref: no) 1.75 (0.55, 5.57) 0.341
TB prophylaxis (ref: no) 0.65 (0.21, 2.03) 0.466
PCP (ref: negative) 1.10 (0.31, 3.89) 0.872
Addiction history (ref: no) 0.28 (0.07, 1.03) 0.056
Education (ref: yes) 1.98 (0.64, 6.17) 0.234
Shared injection history (ref: no) 6.96 (2.46, 19.65) <0.001
CD4 (ref: >200) 4.62 (1.43, 14.90) 0.010
Hosmer–Lemeshow test1: χ2=8.49, p=0.387

OR, odds ratio; CI, confidence interval; TB, tuberculosis; PCP, Pneumocystis carinii pneumonia; ref, reference.

1 The Hosmer–Lemeshow test is a statistical test for goodness-of-fit for logistic regression models. It is used frequently in risk prediction models.

Table 5.
Distribution of Candida strains (n=127) isolated from colonized patients (n=88)
Species Isolation rate by species, n (%) Isolation rate by patients, %
Candida albicans 61 (48.0) 69.3
Candida dubliniensis 29 (22.8) 32.9
Candida glabrata 18 (14.1) 20.4
Candida tropicalis 8 (6.2) 9.1
Candida parapsilosis 5 (3.9) 5.6
Candida guilliermondii 3 (2.3) 3.4
Candida kefyr 3 (2.3) 3.4
Candida krusei 1 (0.7) 1.1
Table 6.
Distribution of co-colonization with different yeast species in 88 colonized patients
Mixed colonization of species Patients, n (%)
C. albicans+C. dubliniensis 6 (6.8)
C. albicans+C. glabrata 5 (5.6)
C. albicans+C. dublinensis+C. glabrata 4 (4.5)
C. dubiliansis+C. glabrata 4 (4.5)
C. albicans+C. tropicalis 2 (2.2)
C. albicans+ C. guilliermondii 2 (2.2)
C. albicans+C. dubilinensis+C. kefyr 1 (1.1)
C. albicans+C. glabrata+C. tropicalis 1 (1.1)
C. dubiliansis+C. parapsilosis 1 (1.1)
C. dubilinensis+C. tropicalis 1 (1.1)
C. glabrata+C. tropicalis 1 (1.1)
C. dubilinensis+C. kefyr 1 (1.1)
  • 1. Dupont B, Graybill JR, Armstrong D, Laroche R, Touze JE, Wheat LJ. Fungal infections in AIDS patients. J Med Vet Mycol 1992;30(Suppl 1):19-28.ArticlePubMedPDF
  • 2. Thompson GR 3rd, Patel PK, Kirkpatrick WR, Westbrook SD, Berg D, Erlandsen J, et al. Oropharyngeal candidiasis in the era of antiretroviral therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:488-495.ArticlePubMedPMC
  • 3. Goulart LS, Souza WW, Vieira CA, Lima JS, Olinda RA, Araújo C. Oral colonization by Candida species in HIV-positive patients: association and antifungal susceptibility study. Einstein (Sao Paulo) 2018;16:eAO4224.ArticlePubMedPMC
  • 4. Patil S, Rao RS, Majumdar B, Anil S. Clinical appearance of oral candida infection and therapeutic strategies. Front Microbiol 2015;6:1391.ArticlePubMedPMC
  • 5. Sardi JC, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJ. Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J Med Microbiol 2013;62:10-24.ArticlePubMed
  • 6. Silva GA, Bernardi TL, Schaker PD, Menegotto M, Valente P. Rapid yeast DNA extraction by boiling and freeze-thawing without using chemical reagents and DNA purification. Braz Arch Biol Technol 2012;55:319-327.ArticlePDF
  • 7. Cassone A, Cauda R. Candida and candidiasis in HIV-infected patients: where commensalism, opportunistic behavior and frank pathogenicity lose their borders. AIDS 2012;26:1457-1472.ArticlePubMed
  • 8. Moris DV, Melhem MS, Martins MA, Mendes RP. Oral Candida spp. colonization in human immunodeficiency virus-infected individuals. J Venom Anim Toxins Incl Trop Dis 2008;14:224-257.ArticlePDF
  • 9. Mushi MF, Mtemisika CI, Bader O, Bii C, Mirambo MM, Groß U, et al. High oral carriage of non-albicans Candida spp. among HIV-infected individuals. Int J Infect Dis 2016;49:185-188.ArticlePubMed
  • 10. Erköse G, Erturan Z. Oral Candida colonization of human immunodeficiency virus infected subjects in Turkey and its relation with viral load and CD4+ T-lymphocyte count. Mycoses 2007;50:485-490.ArticlePubMed
  • 11. Yamada Y, Makimura K, Merhendi H, Ueda K, Nishiyama Y, Yamaguchi H, et al. Comparison of different methods for extraction of mitochondrial DNA from human pathogenic yeasts. Jpn J Infect Dis 2002;55:122-125.PubMed
  • 12. Mirhendi H, Makimura K, Khoramizadeh M, Yamaguchi H. A one-enzyme PCR-RFLP assay for identification of six medically important Candida species. Nihon Ishinkin Gakkai Zasshi 2006;47:225-229.ArticlePubMed
  • 13. Kianipour S, Ardestani ME, Dehghan P. Identification of Candida albicans and Candida dubliniensis species Isolated from bronchoalveolar lavage samples using genotypic and phenotypic methods. Adv Biomed Res 2018;7:66.ArticlePubMedPMC
  • 14. Anwar KP, Malik A, Subhan KH. Profile of candidiasis in HIV infected patients. Iran J Microbiol 2012;4:204-209.PubMedPMC
  • 15. Nanteza M, Tusiime JB, Kalyango J, Kasangaki A. Association between oral candidiasis and low CD4+ count among HIV positive patients in Hoima Regional Referral Hospital. BMC Oral Health 2014;14:143.ArticlePubMedPMC
  • 16. Li YY, Chen WY, Li X, Li HB, Li HQ, Wang L, et al. Asymptomatic oral yeast carriage and antifungal susceptibility profile of HIV-infected patients in Kunming, Yunnan Province of China. BMC Infect Dis 2013;13:46.ArticlePubMedPMC
  • 17. Mushi MF, Bader O, Taverne-Ghadwal L, Bii C, Groß U, Mshana SE. Oral candidiasis among African human immunodeficiency virus-infected individuals: 10 years of systematic review and meta-analysis from sub-Saharan Africa. J Oral Microbiol 2017;9:1317579.ArticlePubMedPMC
  • 18. Patil S, Majumdar B, Sarode SC, Sarode GS, Awan KH. Oropharyngeal candidosis in HIV-infected patients-an update. Front Microbiol 2018;9:980.ArticlePubMedPMC
  • 19. Katiraee F, Teifoori F, Soltani M. Emergence of azole-resistant Candida species in AIDS patients with oropharyngeal candidiasis in Iran. Curr Med Mycol 2015;1:11-16.ArticlePubMedPMCPDF
  • 20. Kwamin F, Nartey NO, Codjoe FS, Newman MJ. Distribution of Candida species among HIV-positive patients with oropharyngeal candidiasis in Accra, Ghana. J Infect Dev Ctries 2013;7:41-45.ArticlePubMed
  • 21. Menezes Rde P, Borges AS, Araujo LB, Pedroso Rdos S, Röder DV. Related factors for colonization by Candida species in the oral cavity of HIV-infected individuals. Rev Inst Med Trop Sao Paulo 2015;57:413-419.ArticlePubMedPMCPDF
  • 22. Nadagir SD, Chunchanur SK, Halesh LH, Yasmeen K, Chandrasekhar MR, Patil BS. Significance of isolation and drug susceptibility testing of non-Candida albicans species causing oropharyngeal candidiasis in HIV patients. Southeast Asian J Trop Med Public Health 2008;39:492-495.PubMed
  • 23. Das PP, Saikia L, Nath R, Phukan SK. Species distribution & antifungal susceptibility pattern of oropharyngeal Candida isolates from human immunodeficiency virus infected individuals. Indian J Med Res 2016;143:495-501.ArticlePubMedPMC
  • 24. Owotade FJ, Patel M. Virulence of oral Candida isolated from HIV-positive women with oral candidiasis and asymptomatic carriers. Oral Surg Oral Med Oral Pathol Oral Radiol 2014;118:455-460.ArticlePubMed
  • 25. Patel PK, Erlandsen JE, Kirkpatrick WR, Berg DK, Westbrook SD, Louden C, et al. The changing epidemiology of oropharyngeal candidiasis in patients with HIV/AIDS in the era of antiretroviral therapy. AIDS Res Treat 2012;2012:262471.ArticlePubMedPMCPDF
  • 26. Sharifzadeh A, Khosravi AR, Shokri H, Sharafi G. Antifungal effect of Trachyspermum ammi against susceptible and fluconazoleresistant strains of Candida albicans. J Mycol Med 2015;25:143-150.ArticlePubMed
  • 27. Khan Z, Ahmad S, Joseph L, Chandy R. Candida dubliniensis: an appraisal of its clinical significance as a bloodstream pathogen. PLoS One 2012;7:e32952.ArticlePubMedPMC
  • 28. Thanyasrisung P, Kesakomol P, Pipattanagovit P, Youngnak-Piboonratanakit P, Pitiphat W, Matangkasombut O. Oral Candida carriage and immune status in Thai human immunodeficiency virus-infected individuals. J Med Microbiol 2014;63:753-759.ArticlePubMed
  • 29. Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America; 2020 [cited 2020 Jun 15]. Available from: https://aidsinfo.nih.gov/guidelines.
  • 30. Perea S, López-Ribot JL, Wickes BL, Kirkpatrick WR, Dib OP, Bachmann SP, et al. Molecular mechanisms of fluconazole resistance in Candida dubliniensis isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis. Antimicrob Agents Chemother 2002;46:1695-1703.ArticlePubMedPMC
  • 31. Quindós G, Carrillo-Muñoz AJ, Arévalo MP, Salgado J, AlonsoVargas R, Rodrigo JM, et al. In vitro susceptibility of Candida dubliniensis to current and new antifungal agents. Chemotherapy 2000;46:395-401.ArticlePubMed
  • 32. Wu CJ, Lee HC, Yang YL, Chang CM, Chen HT, Lin CC, et al. Oropharyngeal yeast colonization in HIV-infected outpatients in southern Taiwan: CD4 count, efavirenz therapy and intravenous drug use matter. Clin Microbiol Infect 2012;18:485-490.ArticlePubMed
  • 33. Manikandan C, Amsath A. Isolation and rapid identification of Candida species from the oral cavity. Int J Pure App Biosci 2013;1:23-27.
  • 34. Bodhade AS, Ganvir SM, Hazarey VK. Oral manifestations of HIV infection and their correlation with CD4 count. J Oral Sci 2011;53:203-211.ArticlePubMed
  • 35. Campo J, Del Romero J, Castilla J, García S, Rodríguez C, Bascones A. Oral candidiasis as a clinical marker related to viral load, CD4 lymphocyte count and CD4 lymphocyte percentage in HIV-infected patients. J Oral Pathol Med 2002;31:5-10.ArticlePubMed
  • 36. Hung CC, Yang YL, Lauderdale TL, McDonald LC, Hsiao CF, Cheng HH, et al. Colonization of human immunodeficiency virus-infected outpatients in Taiwan with Candida species. J Clin Microbiol 2005;43:1600-1603.ArticlePubMedPMC
  • 37. Imam N, Carpenter CC, Mayer KH, Fisher A, Stein M, Danforth SB. Hierarchical pattern of mucosal candida infections in HIVseropositive women. Am J Med 1990;89:142-146.ArticlePubMed
  • 38. McCarthy GM, Mackie ID, Koval J, Sandhu HS, Daley TD. Factors associated with increased frequency of HIV-related oral candidiasis. J Oral Pathol Med 1991;20:332-336.ArticlePubMed
  • 39. Ceballos Salobreña A, Gaitán Cepeda LA, Ruesga MT, Ceballos García L, Quindós G. Prevalence of oral lesions by Candida sp.: their varieties and serotypes in a population of patients with AIDS under a highly active antiretroviral therapy. Rev Iberoam Micol 1998;15:141-145 (Spanish).PubMed
  • 40. Katiraee F, Khosravi AR, Khalaj V, Hajiabdolbaghi M, Khaksar A, Rasoolinejad M, et al. Oropharyngeal candidiasis and oral yeast colonization in Iranian human immunodeficiency virus positive patients. J Mycol Med 2010;20:8-14.Article
  • 41. Joulaei H, Lankarani KB, Kazerooni PA, Marzban M. Number of HIV-infected cases in Iran: true or just an iceberg. Indian J Sex Transm Dis AIDS 2017;38:157-162.ArticlePubMedPMC
  • 42. Putranti A, Asmarawati TP, Rachman BE, Hadi U. Oral candidiasis as clinical manifestation of HIV/AIDS infection in Airlangga University hospital patients. IOP Conf Ser Earth Environ Sci 2018;125:012063.Article
  • 43. Owotade FJ, Patel M, Ralephenya TR, Vergotine G. Oral Candida colonization in HIV-positive women: associated factors and changes following antiretroviral therapy. J Med Microbiol 2013;62:126-132.ArticlePubMed
  • 44. Shiboski CH, Chen H, Ghannoum MA, Komarow L, Evans S, Mukherjee PK, et al. Role of oral candidiasis in TB and HIV coinfection: AIDS Clinical Trial Group Protocol A5253. Int J Tuberc Lung Dis 2014;18:682-688.ArticlePubMedPMC
  • 45. Campisi G, Pizzo G, Milici ME, Mancuso S, Margiotta V. Candidal carriage in the oral cavity of human immunodeficiency virus-infected subjects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:281-286.ArticlePubMed
  • 46. Gottfredsson M, Cox GM, Indridason OS, de Almeida GM, Heald AE, Perfect JR. Association of plasma levels of human immunodeficiency virus type 1 RNA and oropharyngeal Candida colonization. J Infect Dis 1999;180:534-537.ArticlePubMedPDF

Figure & Data

References

    Citations

    Citations to this article as recorded by  
    • Antifungal Susceptibility and Candida sp. Biofilm Production in Clinical Isolates of HIV-Positive Brazilian Patients under HAART Therapy
      Anelise Maria Costa Vasconcelos Alves, Érika Helena Salles de Brito, Márcio Flávio Moura de Araújo, Juliana Jales de Hollanda Celestino, Ana Caroline Rocha de Melo Leite, Gabriela Silva Cruz, Nuno Filipe Azevedo, Célia Fortuna Rodrigues
      Biomedicines.2024; 12(2): 310.     CrossRef
    • Exploring the diversity of uncommon oral yeast species and associated risk factors among substance abusers in southwestern Iran
      Aynaz Ghojoghi, Sadegh Khodavaisy, Ali Zarei Mahmoudabadi, Eisa Nazar, Mahnaz Fatahinia
      Scientific Reports.2024;[Epub]     CrossRef
    • Etiopathogenetic Features of Dermatomycosis in HIV- Infected Patients
      Iryna Kravchuk
      The Ukrainian Scientific Medical Youth Journal.2024; 150(4): 60.     CrossRef
    • Recuento de linfocitos CD4, carga viral y colonización oral por Candida en personas viviendo con VIH/SIDA
      Esperanza Gissela Vargas-Díaz, Graciela Albino Cornejo, Hans Ramón Quiroz-Ruiz
      Gaceta Médica Boliviana.2023; 46(1): 18.     CrossRef
    • Low level of antifungal resistance inCandidaspecies recovered from Iranian HIV-associated oral infection
      Maryam Erfaninejad, Ali Zarei Mahmoudabadi, Elham Maraghi, Mohammad Hashemzadeh, Mahnaz Fatahinia
      Letters in Applied Microbiology.2023;[Epub]     CrossRef
    • Epidemiology, prevalence, and associated factors of oral candidiasis in HIV patients from southwest Iran in post-highly active antiretroviral therapy era
      Maryam Erfaninejad, Ali Zarei Mahmoudabadi, Elham Maraghi, Mohammad Hashemzadeh, Mahnaz Fatahinia
      Frontiers in Microbiology.2022;[Epub]     CrossRef
    • Meyerozyma guilliermondii species complex: review of current epidemiology, antifungal resistance, and mechanisms
      Reza Ghasemi, Ensieh Lotfali, Kamran Rezaei, Seyed Ataollah Madinehzad, Mahdi Falah Tafti, Nikta Aliabadi, Ebrahim Kouhsari, Mahsa Fattahi
      Brazilian Journal of Microbiology.2022; 53(4): 1761.     CrossRef
    • HIV-infected patients rarely develop invasive fungal diseases under good immune reconstitution after ART regardless high prevalence of pathogenic filamentous fungi carriage in nasopharynx/oropharynx
      Xiaoman Chen, Yi Cao, Meijun Chen, Haodi Wang, Peishan Du, Hong Li, Huolin Zhong, Quanmin Li, Santao Zhao, Zhenjiang Yao, Wanshan Chen, Weiping Cai, Xiaoping Tang, Linghua Li
      Frontiers in Microbiology.2022;[Epub]     CrossRef
    • Neglected mycobiome in HIV infection: Alterations, common fungal diseases and antifungal immunity
      Shuang Li, Xiaodong Yang, Christiane Moog, Hao Wu, Bin Su, Tong Zhang
      Frontiers in Immunology.2022;[Epub]     CrossRef
    • Identification & Correlation of Candida Strains with CD4+ Count Among HIV Patients on HAART and Evaluation of In-Vitro Susceptibility to Fluconazole and Voriconazole
      Naidu Harika, Koduri Sridevi, Buduru Krishnaveni, Nalli Prasanth Kumar, Gutta Mounika, Adari Devi Naga Deepika
      Journal of Indian Academy of Oral Medicine and Radiology.2022; 34(1): 38.     CrossRef
    • Update of the list of QPS‐recommended biological agents intentionally added to food or feed as notified to EFSA 13: suitability of taxonomic units notified to EFSA until September 2020
      Kostas Koutsoumanis, Ana Allende, Avelino Alvarez‐Ordóñez, Declan Bolton, Sara Bover‐Cid, Marianne Chemaly, Robert Davies, Alessandra De Cesare, Friederike Hilbert, Roland Lindqvist, Maarten Nauta, Luisa Peixe, Giuseppe Ru, Marion Simmons, Panagiotis Skan
      EFSA Journal.2021;[Epub]     CrossRef
    • Transcription Factors of CAT1, EFG1, and BCR1 Are Effective in Persister Cells of Candida albicans-Associated HIV-Positive and Chemotherapy Patients
      Elham Aboualigalehdari, Maryam Tahmasebi Birgani, Mahnaz Fatahinia, Mehran Hosseinzadeh
      Frontiers in Microbiology.2021;[Epub]     CrossRef

    Oral colonization by Candida species and associated factors in HIV-infected patients in Ahvaz, southwest Iran
    Oral colonization by Candida species and associated factors in HIV-infected patients in Ahvaz, southwest Iran
    Primers Reference
    ITS1 5´-TCC-GTA-GGT-GAA-CCTGCG-G-3´ [9]
    ITS4 5´-TCC-TCC-GCT-TAT-TGA-TAT-GC-3´
    CALF 5´-TGGTAAGGCGGGATCGCTT-3´ [13]
    CALR 5´-GGTCAAAGTTTGAAGATATAC-3´
    CDUF 5´-AA ACTTGTCACGAGATTATTTTT-3´ [13]
    CDUR 5´-AAA GTTTGAAGAATAAAATGGC-3
    Variables Colonized (n=88) Non-colonized (n=113) p-value1
    Sex
     Male 63 (54.8) 52 (45.2) <0.001
     Female 25 (29.1) 61 (70.9)
    Drug injection
     True 47 (57.3) 35 (42.7) 0.001
     False 41 (34.5) 78 (65.5)
    TB
     Yes 15 (68.2) 7 (31.8) 0.015
     No 73 (40.8) 106 (59.2)
    TB prophylaxis
     Yes 6 (30.0) 14 (70.0) 0.191
     No 82 (45.3) 99 (54.7)
    PCP
     Positive 12 (63.2) 7 (36.8) 0.074
     Negative 76 (41.8) 106 (58.2)
    ARV
     Yes 85 (42.9) 113 (57.1) 0.082
     No 3 (100) 0 (0.0)
    Blood transfusion
     True 1 (100) 0 (0.0) 0.438
     False 87 (43.5) 113 (56.5)
    Mother-to-child transmission
     True 3 (60.0) 2 (40.0) 0.655
     False 85 (43.4) 111 (56.6)
    Addiction history
     Yes 51 (49.5) 52 (50.5) 0.093
     No 37 (37.8) 61 (62.2)
    Education
     No education 11 (57.9) 8 (42.1) 0.1932
     Elementary education 75 (41.7) 105 (58.2)
     Higher education 2 (100) 0 (0.0)
    Homosexuality
     True 5 (71.4) 2 (28.6) 0.244
     False 83 (42.8) 111 (57.2)
    HCV Ag
     Positive 31 (50.0) 31 (50.0) 0.235
     Negative 57 (41.0) 82 (59.0)
    HBV Ag
     Positive 4 (50.0) 4 (50.0) 0.732
     Negative 84 (43.5) 109 (56.5)
    Occupational exposure
     True 1 (50.0) 1 (50.0) 1.000
     False 87 (43.7) 112 (56.3)
    Shared injection history
     Yes 37 (72.5) 14 (27.5) <0.001
     No 51 (34.0) 99 (66.0)
    CD4 count (cells/mm3)
     ≤200 20 (80.0) 5 (20.0) <0.001
     >200 68 (38.6) 108 (61.4)
    Variables Colonized
    		 Non-colonized
    		 p-value1
    n Mean±SD n Mean±SD
    Age 88 40.61±12.55 113 37.15±8.18 0.005
    Viral load 36 802,637.71±2,544,107.27 27 3,150,032.340±11,343,051.38 0.064
    Candida load 88 5,787.51±23,256.64 58 3.50±2.12 <0.001
    Variables OR (95% CI) p-value
    Sex (ref: female) 3.59 (1.23, 10.46) 0.019
    Age 1.01 (0.98, 1.04) 0.376
    Drug injection (ref: false) 0.78 (0.22, 2.68) 0.697
    TB (ref: no) 1.75 (0.55, 5.57) 0.341
    TB prophylaxis (ref: no) 0.65 (0.21, 2.03) 0.466
    PCP (ref: negative) 1.10 (0.31, 3.89) 0.872
    Addiction history (ref: no) 0.28 (0.07, 1.03) 0.056
    Education (ref: yes) 1.98 (0.64, 6.17) 0.234
    Shared injection history (ref: no) 6.96 (2.46, 19.65) <0.001
    CD4 (ref: >200) 4.62 (1.43, 14.90) 0.010
    Hosmer–Lemeshow test1: χ2=8.49, p=0.387
    Species Isolation rate by species, n (%) Isolation rate by patients, %
    Candida albicans 61 (48.0) 69.3
    Candida dubliniensis 29 (22.8) 32.9
    Candida glabrata 18 (14.1) 20.4
    Candida tropicalis 8 (6.2) 9.1
    Candida parapsilosis 5 (3.9) 5.6
    Candida guilliermondii 3 (2.3) 3.4
    Candida kefyr 3 (2.3) 3.4
    Candida krusei 1 (0.7) 1.1
    Mixed colonization of species Patients, n (%)
    C. albicans+C. dubliniensis 6 (6.8)
    C. albicans+C. glabrata 5 (5.6)
    C. albicans+C. dublinensis+C. glabrata 4 (4.5)
    C. dubiliansis+C. glabrata 4 (4.5)
    C. albicans+C. tropicalis 2 (2.2)
    C. albicans+ C. guilliermondii 2 (2.2)
    C. albicans+C. dubilinensis+C. kefyr 1 (1.1)
    C. albicans+C. glabrata+C. tropicalis 1 (1.1)
    C. dubiliansis+C. parapsilosis 1 (1.1)
    C. dubilinensis+C. tropicalis 1 (1.1)
    C. glabrata+C. tropicalis 1 (1.1)
    C. dubilinensis+C. kefyr 1 (1.1)
    Table 1. List of primers used in this study

    Table 2. The frequency of socio-demographic characteristics of the study subjects

    Values are presented as number (%).

    TB, tuberculosis; PCP, Pneumocystis carinii pneumonia; ARV, antiretroviral; HCV, hepatitis C virus; HBV, hepatitis B virus; Ag, antigen.

    Chi-square test or Fisher exact test.

    Tests were performed after pooling the last 2 groups (elementary education, higher education) in order to eliminate small expected frequencies.

    Table 3. Characteristics of the study population

    SD, standard deviation.

    Mann-Whitney test.

    Table 4. Prevalence rates of oral colonization by Candida species

    OR, odds ratio; CI, confidence interval; TB, tuberculosis; PCP, Pneumocystis carinii pneumonia; ref, reference.

    The Hosmer–Lemeshow test is a statistical test for goodness-of-fit for logistic regression models. It is used frequently in risk prediction models.

    Table 5. Distribution of Candida strains (n=127) isolated from colonized patients (n=88)

    Table 6. Distribution of co-colonization with different yeast species in 88 colonized patients

    Table 1.

    Table 2.

    Table 3.

    Table 4.

    Table 5.

    Table 6.

    Epidemiol Health : Epidemiology and Health
    © Korean Society of Epidemiology.
    TOP