Oral mycobiome identification in atopic dermatitis, leukemia, and HIV patients – a systematic review

Figures & data

Figure 1. Flow chart of selection process. Database search was performed from January 2009 to September 2019.

Table 1. Quality assessment of the selected studies for the systematic review.

ITEM	QUALITY ASSESSMENT	YES	NO
1	Representative sample of the population	1	0
2	Definition of study type	1	0
3	Definition of inclusion and exclusion criteria for the target population	1	0
4	Presence of control group	1	0
5	Colorimetric and morphological identification of fungal species	1	0
6	Identification of species by biochemical tests for sugar fermentation and assimilation and/or mass spectrometry	1	0
7	Identification of fungal species by PCR and molecular analysis	1	0
8	Statistical analysis	1	0
9	Discussion of study limitations	1	0

Table 2. Description of studies selected by the quality assessment.

Authors, country and year	Databases	Keywords	Disease studied Type of study	Sample size	Sample type	Quality Assesment
Das Chagas et al. Brazil 2009 [50]	Pubmed	Fungi; mouth; HIV	Human immunodeficiency syndrome (HIV)	30 children with HIV	Oral swab and decayed dentin	B
			Does not mention the type of study
Junqueira et al. Brazil 2012 [51]	LilaCS	Fungi; HIV	Human immunodeficiency syndrome (HIV)	60 soropositive patients with oropharyngeal candidacy	Oral swab from the Candida injury site, and Saliva	B
			Does not mention the type of study
Mane et al. India 2012 [70]	LilaCS	Fungi; HIV	Human immunodeficiency syndrome (HIV)	335 patients: 210 HIV-positive 125 HIV-negative	Oral swab	A
			Prospective study
De Mendonça et al. Brazil 2012 [62]	Web of Science	Fungi; microbiota; leukemia	Leukemia	71 pediatric patients	Saliva	B
			Cohort study
Moris et al. Brazil 2012 [52]	LilaCS	Fungi; HIV	Human immunodeficiency syndrome (HIV)	214 HIV-positive patients	Oral swab	B
			Does not mention the type of study
Dos Santos Abrantes et al. South Africa and Cameroon 2013 [54]	LilaCS	Fungi; HIV	Human immunodeficiency syndrome (HIV)	212 HIV-positive patients 262 HIV-negative patients	Oral swab	B
			Does not mention the type of study
Merenstein et al. USA 2013 [55]	LilaCS	Fungi; HIV	Human immunodeficiency syndrome (HIV)	84 women: 59 HIV-positive women 25 HIV-negative women	Oral swab	A
			Non-interventional prospective cohort study
Li YY et al. China 2013 [47]	LilaCS	Fungi; mycobiome; HIV	Human immunodeficiency syndrome (HIV)	604 HIV-positive patients 851 HIV-negative individuals	Oral tongue and mucosa swab	A
Sharifzadeh et al. Iran 2013 [56]	Pubmed	Fungi; HIV	Human immunodeficiency syndrome (HIV)	100 HIV-positive patients	Oral tongue swab, oral mucosa and lesions	B
	LilaCS	Fungi; microbiota; HIV	Does not mention the type of study
Jiang et al. China 2014 [57]	Pubmed	Fungi; mouth; HIV	Human immunodeficiency syndrome (HIV)	45 HIV- positive adult patients 31 systemically healthy individuals	Oral rinses	A
	LilaCS	Fungi; HIV	Prospective study
Mukherjee et al. USA 2014 [44]	Pubmed	Fungi; HIV	Human immunodeficiency syndrome (HIV)	12 HIV-positive patients 12 systemically healthy individuals	Oral rinses	B
	Web of Science	Fungi; mouth; microbiota; HIV	Does not mention the type of study
Thanyasrisung et al. Thailand 2014 [58]	LilaCS	Fungi; HIV	Human immunodeficiency syndrome (HIV)	60 HIV-patients 49 systemically healthy individuals	Oral rinses	A
			Does not mention the type of study
Javad et al. Iran 2015 [36]	Pubmed	Atopic dermatitis; Fungi	Atopic dermatitis (AD)	100 patients with AD 50 systemically healthy individuals	Oral swab and scalpel	B
			Does not mention the type of study
Blignaut et al. South Africa 2015 [72]	Pubmed	Fungi; HIV	Human immunodeficiency syndrome (HIV)	362 HIV-positive children	Tongue and dentine swab	A
	LilaCS	Fungi; mouth; HIV	Cohort study
Menezes et al. Brazil 2015 [59]	Pubmed	Fungi; HIV	Human immunodeficiency syndrome (HIV)	147 HIV-positive patients	Unstimulated saliva	B
			Cross-sectional study
De Mendonça et al. Brazil 2015 [61]	Pubmed	Fungi; microbiota; leukemia	Acute lymphoblastic leukemia (ALL)	71 pediatric patients with ALL aged between 3 and 276 months	Oral mucosa material and blood sample	B
	Web of Science		Cohort study
Mushi et al. Tanzania 2016 [73]	Pubmed	Fungi; mouth; HIV	Human immunodeficiency syndrome (HIV))	351 HIV-positive patients 639 HIV-negative patients	Oral rinses	B
			Transverse cohort study
Lourenço et al. Brazil 2017 [60]	Pubmed	Fungi; mouth; HIV	Human immunodeficiency syndrome (HIV)	25 HIV-negative patients 48 HIV-positive patients	Oral rinses	A
			Does not mention the type of study
Fukui et al. Japan 2018 [45]	Pubmed	Fungi; mycobiome; HIV	Human immunodeficiency syndrome (HIV))	46 HIV-positive patients 20 HIV-negative patients	Palatine tonsil swab	A
			Cross-sectional study
Mukherjee et al. USA 2018 [53]	Pubmed	Fungi; HIV Fungi; mouth; microbiota; HIV Fungi; mycobiome; HIV	Human immunodeficiency syndrome (HIV)	24 HIV-negative individuals 72 HIV-positive patients	Oral rinses	A
	Web of Science		Cohort study
Vijendran et al. India 2018 [46]	Pubmed	Fungi; HIV	Human immunodeficiency syndrome (HIV)	100 HIV-positive patients 100 HIV-negative patients	Tongue-dorsum swab	A
	Google Scholar		Prospective study

Table 3. Isolated species and study objectives.

Authors, country and year	Goals	Main outcome	Identification method	Fungi species isolated
Das Chagas et al. Brazil 2009 [50]	Evaluate oral mucosal Candida species of children with HIV before and after dental treatment.	After dental treatment, there was a reduction of Candida in the oral mucosa.	Colorimetric and morphological identification and sugar fermentation and assimilation tests	C. albicans C. tropicalis C. parapsilosis
Junqueira et al. Brazil 2012 [51]	To evaluate the presence of pathogenic yeasts of saliva and oropharyngeal candidiasis in HIV-positive patients	Brazilian HIV patients are colonized and infected with yeasts composed of different species such as Candida, non-albicans species and other species	Sugar fermentation and assimilation tests (API20 C); and morphological tests: germ-tube test, hyphae production, cornmeal agar chlamydospore	C. albicans C. dubliniensis
Mane et al. India 2012 [70]	To determine the biofilm production of Candida isolates from HIV-positive and HIV-negative patients	There was an improvement in the ability to form oral Candida isolates from HIV-positive individuals compared to non-infected individuals	Sugar fermentation and assimilation tests (API 20AUX)	C. parapsilosis C. glabrata C. tropicalis C. krusei C. lusitaniae C. kefyr
De Mendonça et al. Brazil 2012 [62]	To prospectively investigate associations between HSV-1; Candida spp; and oral bacteria with the oral mucositis severity	The presence of HSV-1 and Candida was associated to oral mucositis severity in all pediatric patients	Colorimetric and morphological identification	C. spp.
Moris et al. Brazil 2012 [52]	To distinguish species from a C parapsilosis complex isolated from HIV-positive individuals	C metapsilosis is a commensal fungus but its importance as a pathogen must be confirmed	Colorimetric and morphological identification and molecular techniques (PCR/RFLP)	C. parapsilosis C. albicans C. glabrata C. tropicalis C. dubliniensis C. krusei
Dos Santos Abrantes et al. South Africa and Cameroon 2013 [54]	To determine the prevalence of Candida species	Drug resistance is common in HIV patients from South Africa and Cameroon	Colorimetric and morphological identification; germ-tube test and gram coloring	C. albicans C. glabrata C. tropicalis C. dubliniensis
Merenstein et al. USA 2013 [55]	Compare the colonization proportions of oral and vaginal Candida in HIV-positive and negative patients.	Oral and vaginal Candida colonization was more frequent in HIV-positive participants than in HIV-negative controls.	Sugar fermentation and assimilation tests (API20 C); morphological tests: germ tube, culture media for chlamydospores production	C. parapsilosis C. albicans C. glabrata C. tropicalis C. lusitaniae
Li YY et al. China 2013 [47]	To investigate oral transport rate of asymptomatic Candida, its species distribution and fungal susceptibility.	Oral fungi colonization is associated with CD4+ cells count and retroviral therapy.	Colorimetric and morphological identification; sugar fermentation and assimilation tests (API20 C); morphological tests: germ tube, culture media for chlamydospores and xylose assimilation.	C. glabrata, C. parapsilosis, C. krusei, C. tropicalis, C. rugosa, C. norvegensis, Pichia ohmeri Saccharomyces cerevisiae
Sharifzadeh et al. Iran 2013 [56]	To evaluate prevalence of pathogenic organisms with oropharyngeal candidiasis-related Candida species in HIV-positive patients.	Oral Candida is not associated with CD4+ cells count except when the count is above 400 cells/µl	Molecular method (PCR) and morphological tests: germ tube, hyphae production and culture media for chlamydospores production	C. parapsilosis C. albicans C. glabrata C. tropicalis C. dubliniensis C. krusei C. lusitaniae C. guilliermondii C. norvegensis Kluyveromyces Cr. albidus
Jiang et al. China 2014 [57]	To investigate oral Candida presence, its distribution and anti-fungal susceptibility during the first year of antiretroviral therapy in HIV-positive adults.	Rise of CD4+ cells count is associated with less Candida presence.	Sugar fermentation and assimilation test (API20 C); morphological tests: germ tube, hyphae production and culture media for chlamydospores production	C. parapsilosis C. albicans C. glabrata C. tropicalis C. dubliniensis C. krusei C. kefyr C. guilliermondii C. norvegensis C. rugosa C. sphaerica Rhodotorula glutinis
Mukherjee et al. USA 2014 [44]	To identify main mycobiome and bacteriome in HIV-positive and HIV-negative individuals.	More Candida colonization was associated with less Pichia abundance.	Molecular methods (PCR) Pyrosequencing for mycobiome analysis (MTPS)	Mycobiome identification. Some identified genera were: Candida, Aspergillus, Fusarium and Pichia
Thanyasrisung et al. Thailand 2014 [58]	To determinate Candida species prevalence in HIV-positive adults.	Candida colonization is influenced by immune status, tuberculosis presence and contraceptive use	Colorimetric and morphological identification; sugar fermentation and assimilation test (API20 C); morphological test: culture media for chlamydospores production; molecular method (PCR)	C. parapsilosis C. glabrata C. tropicalis C. dubliniensis C. krusei C. lusitaniae
Javad et al. Iran 2015 [36]	To verify Candida colonization and to verify humoral-specific response against C. albicans in AD patients.	IgG-levels in sera from AD patients were significantly lower than in controls.	Colorimetric and morphological identification; molecular method (PCR)	C. parapsilosis C. albicans C. glabrata C. dubliniensis
Blignaut et al. South Africa 2015 [72]	To demonstrate C. albicans presence in soft and hard tissues and to investigate by molecular techniques the genetic subtype from two different oral sites.	Decayed teeth can be considered potential C. albicans reservoirs, and they can cause infection in immunocompromised patients.	Colorimetric and morphological identification; morphological test: germ tube; sugar fermentation and assimilation test (ID32 C); molecular method (DGGE)	C. albicans
Menezes et al. Brazil 2015 [59]	To evaluate and quantify Candida species	Low CD4+ cells count is associated with high yeast density in HIV-positive patients.	Colorimetric and morphological identification; sugar fermentation and assimilation test (Auxacolor2 system); molecular method (PCR)	C. parapsilosis C. albicans C. glabrata C. tropicalis C. dubliniensis C. krusei C. lusitaniae C. kefyr C. guilliermondii C. peliculosa C. famata
De Mendonça et al. Brazil 2015 [61]	To investigate associations between oral microbiota, white cells, neutrophil and platelet counts and hemoglobin levels.	Presence of Candida species is associated with mucositis worsening in children and adolescents.	Morphological tests.	Candida spp.
Mushi et al. Tanzania 2016 [73]	To compare Candida non-albicans colonization in HIV-positive and HIV-negative individuals from Mwanza, Tanzania.	Candida non-albicans frequency is higher in HIV-positive individuals with a low CD4+ cell count that can facilitate invasive infections.	Colorimetric and morphological identification; mass spectrometry (MALDI-TOF MS)	C. glabrata C. tropicalis C. dubliniensis C. krusei
Lourenço et al. Brazil 2017 [60]	To verify periodontal effects in prevalence of Candida species.	Periodontal disease is associated with an increase in Candida species in HIV-positive patients.	Colorimetric and morphological identification; morphological tests: micro cultivated fungi test, hypertonic Sabouraud broth, germ tube test, tetrazolium reduction, hyphae production, culture media for chlamydospores production; sugar fermentation and assimilation tests: API (ID 32 C).	C. parapsilosis C. albicans C. glabrata C. tropicalis C. dubliniensis C. krusei
Fukui et al. Japan 2018 [45]	To characterize tonsil microbiome in HIV-positive patients.	There is dysbiosis in tonsil microbiome of HIV-positive patients in an immune status-independent manner.	DNA sequencing and bioinformatics.	C. spp. Malassezia Saccharomyces Debaryomyces Aspergillus Penicillum
Mukherjee et al. USA 2018 [53]	To verify a relationship between microbial dysbiosis, smoking and HIV markers.	Clinical and immune variables of HIV patients are related to oral microbiota dysbiosis	DNA sequencing and bioinformatics.	C. parapsilosis C. albicans C. tropicalis C. dubliniensis C. lusitaniae C. rugosa C. orthopsilosis C. oxycetoniae C. versatilis C. ethanolica C. spp.
Vijendran et al. India 2018 [46]	To verify clinical spectrum of surface mycoses, its microbial etiology and the antifungal-resistance pattern.	Isolated species from HIV-positive patients demonstrated increased resistance to antifungals.	Colorimetric and morphological identification; morphological tests: germ tube test, spore formation test; sugar fermentation and assimilation tests.	Dermatophytes Pityrosporum Non-dermatophyte Candida spp.

Figure 2. Most frequent methods used to identify fungi. Mycobiome identification can be divided into 7 general approaches, with each one presenting advantages and disadvantages.

Figure 3. Comparison of fungal profiling approaches by the selected studies. (a) Identification methods used by studies published between years 2009–2014. (b) Identification methods used by studies published between years 2015–2018.

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