An Association of Cryptococcus neoformans/ C. gattii Genotype and HIV Status in Asia: A Systematic Review

Objective: It has been known that VNI molecular type of Cryptococcus neoformans/C. gattii is strongly associated  with HIV patients. However, this paradigm has recently been challenged because of the high prevalence of VNI molecular type among non-HIV patients with cryptococcosis in East Asia. The purpose of this study was to answer the question: “Among cryptococcosis in Asia, is there an association between the genotype and the patient’s HIV status?” Methods: Using a systematic review and meta-analysis study design, we included all relevant published data, which were any type of study designs, mainly studied clinical Cryptococcus neoformans/C. gattii strains isolated in Asia and had available molecular typing data. The primary study variables were Cryptococcus neoformans molecular type (VNI/non-VNI or ST5/non-ST5) and the HIV status of the patients at the time of diagnosis. We used a randomeffects meta-analysis model to estimate the prevalence of HIV infection. Results: Sixteen retrospective descriptive studies during 2005 – 2018 (1,584 isolates) were included. Most of the cryptococcosis cases in East Asian countries were in non-HIV patients (72.4-81.8%), which differed from non-East Asian countries (2.6-28.3% associated with non-HIV patients). In East Asia, the HIV prevalence among VNI and ST5 infected patients ranged from 7.5% - 46.7% with the pooled prevalence of 19.8% (95% CI, 12.2% - 30.4%) and 5.3% - 52.4% with the pooled prevalence of 19.9% (95% CI, 6.9% - 45.3%), respectively. In non-East Asia, the HIV prevalence among VNI and ST5 infected patients ranged from 48.3% - 98.8% with the pooled prevalence of 81.9% (95% CI, 73.3% - 88.2%) and 52.3% - 88.0% with the pooled prevalence of 74.9% (95% CI, 40.7% - 92.8%), respectively. Statistical heterogeneity was high in both analyses with the I2 of 79-89% in all analyses. Conclusion: Our results confirmed the low prevalence of HIV prevalence among VNI and ST5 strains in East Asian countries. The emergence of high virulence genotype causing disease in non-HIV patient is highly unlikely, because the VNI and ST5 were associated with HIV patients in other Asian countries. It can be hypothesized that the low HIV prevalence among VNI and ST5 strains in East Asian is due to the high susceptibility to cryptococcosis of people living in this region. This requires further investigation

An Association of Cryptococcus Neoformans/C. gattii Genotype and HIV Status in Asia: A Systematic Review

Objective: It has been known that VNI molecular type of Cryptococcus neoformans/C. gattii is strongly associated with HIV patients. However, this paradigm has recently been challenged because of the high prevalence of VNI molecular type among non-HIV patients with cryptococcosis in East Asia. The purpose of this study was to answer the question: “Among cryptococcosis in Asia, is there an association between the genotype and the patient’s HIV status?”. Methods: Using a systematic review and meta-analysis study design, we included all relevant published data, which were any type of study designs, mainly studied clinical Cryptococcus neoformans/C. gattii strains isolated in Asia and had available molecular typing data. The primary study variables were Cryptococcus neoformans molecular type (VNI/non-VNI or ST5/non-ST5) and the HIV status of the patients at the time of diagnosis. We used a random-effects meta-analysis model to estimate the prevalence of HIV infection. Results: Sixteen retrospective descriptive studies during 2005 – 2018 (1,584 isolates) were included. Most of the cryptococcosis cases in East Asian countries were in non-HIV patients (72.4-81.8%), which differed from non-East Asian countries (2.6-28.3% associated with non-HIV patients). In East Asia, the HIV prevalence among VNI and ST5 infected patients ranged from 7.5% - 46.7% with the pooled prevalence of 19.8% (95% CI, 12.2% - 30.4%) and 5.3% - 52.4% with the pooled prevalence of 19.9% (95% CI, 6.9% - 45.3%), respectively. In non-East Asia, the HIV prevalence among VNI and ST5 infected patients ranged from 48.3% - 98.8% with the pooled prevalence of 81.9% (95% CI, 73.3% - 88.2%) and 52.3% - 88.0% with the pooled prevalence of 74.9% (95% CI, 40.7% - 92.8%), respectively. Statistical heterogeneity was high in both analyses with the I2 of 79-89% in all analyses. Conclusion: Our results confirmed the low prevalence of HIV prevalence among VNI and ST5 strains in East Asian countries. The emergence of high virulence genotype causing disease in non-HIV patient is highly unlikely, because the VNI and ST5 were associated with HIV patients in other Asian countries. It can be hypothesized that the low HIV prevalence among VNI and ST5 strains in East Asian is due to the high susceptibility to cryptococcosis of people living in this region. This requires further investigation

Resistance of Asian Cryptococcus neoformans Serotype A Is Confined to Few Microsatellite Genotypes

Contains fulltext : 109375.pdf (publisher's version ) (Open Access)BACKGROUND: Cryptococcus neoformans is a pathogenic yeast that causes cryptococcosis, a life threatening disease. The prevalence of cryptococcosis in Asia has been rising after the onset of the AIDS epidemic and estimates indicate more than 120 cases per 1,000 HIV-infected individuals per year. Almost all cryptococcal disease cases in both immunocompromised and immunocompetent patients in Asia are caused by C. neoformans var. grubii. Epidemiological studies on C. neoformans in pan-Asia have not been reported. The present work studies the genetic diversity of the fungus by microsatellite typing and susceptibility analysis of approximately 500 isolates from seven Asian countries. METHODOLOGY/PRINCIPAL FINDINGS: Genetic diversity of Asian isolates of C. neoformans was determined using microsatellite analysis with nine microsatellite markers. The analysis revealed eight microsatellite complexes (MCs) which showed different distributions among geographically defined populations. A correlation between MCs and HIV-status was observed. Microsatellite complex 2 was mainly associated with isolates from HIV-negative patients, whereas MC8 was associated with those from HIV-positive patients. Most isolates were susceptible to amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole, but 17 (3.4%) and 10 (2%) were found to be resistant to 5-flucytosine and fluconazole, respectively. Importantly, five Indonesian isolates (approximately 12.5% from all Indonesian isolates investigated and 1% from the total studied isolates) were resistant to both antifungals. The majority of 5-flucytosine resistant isolates belonged to MC17. CONCLUSIONS: The findings showed a different distribution of genotypes of C. neoformans var. grubii isolates from various countries in Asia, as well as a correlation of the microsatellite genotypes with the original source of the strains and resistance to 5-flucytosine

Low diversity Cryptococcus neoformans variety grubii multilocus sequence types from Thailand are consistent with an ancestral African origin.

Published versio

Banana blossom agar (BABA), a new medium to isolate members of the Cryptococcus neoformans/Cryptococcus gattii species complex useful for resource limited countries

Isolation of representatives of the Cryptococcus neoformans/Cryptococcus gattii species complex can be made using dopamine containing media, such as Niger seed agar and l-DOPA agar. Here, we describe an alternative medium that uses banana flowers. Banana is a dopamine containing fruit and is widely available in tropical and subtropical countries that have high numbers of cryptococcosis patients. This banana blossom-based agar is useful for the enrichment of isolates of the C. neoformans/C. gattii species complex from environmental and clinical materials. The banana blossom agar (BABA) with and without creatinine can differentiate between the melanin forming isolates of the C. neoformans/C. gattii species complex from other yeasts that do not form melanin

Identification of Medically Relevant Species of Arthroconidial Yeasts by Use of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry

<p>Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was used for an extensive identification study of arthroconidial yeasts, using 85 reference strains from the CBS-KNAW yeast collection and 134 clinical isolates collected from medical centers in Qatar, Greece, and Romania. The test set included 72 strains of ascomycetous yeasts (Galactomyces, Geotrichum, Saprochaete, and Magnusiomyces spp.) and 147 strains of basidiomycetous yeasts (Trichosporon and Guehomyces spp.). With minimal preparation time, MALDI-TOF MS proved to be an excellent diagnostic tool that provided reliable identification of most (98%) of the tested strains to the species level, with good discriminatory power. The majority of strains were correctly identified at the species level with good scores (> 2.0) and seven of the tested strains with log score values between 1.7 and 2.0. The MALDI-TOF MS results obtained were consistent with validated internal transcribed spacer (ITS) and/or large subunit (LSU) ribosomal DNA sequencing results. Expanding the mass spectrum database by increasing the number of reference strains for closely related species, including those of nonclinical origin, should enhance the usefulness of MALDI-TOF MS-based diagnostic analysis of these arthroconidial fungi in medical and other laboratories.</p>

Identification of Medically Relevant Species of Arthroconidial Yeasts by Use of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was used for an extensive identification study of arthroconidial yeasts, using 85 reference strains from the CBS-KNAW yeast collection and 134 clinical isolates collected from medical centers in Qatar, Greece, and Romania. The test set included 72 strains of ascomycetous yeasts (Galactomyces, Geotrichum, Saprochaete, and Magnusiomyces spp.) and 147 strains of basidiomycetous yeasts (Trichosporon and Guehomyces spp.). With minimal preparation time, MALDI-TOF MS proved to be an excellent diagnostic tool that provided reliable identification of most (98%) of the tested strains to the species level, with good discriminatory power. The majority of strains were correctly identified at the species level with good scores (&gt; 2.0) and seven of the tested strains with log score values between 1.7 and 2.0. The MALDI-TOF MS results obtained were consistent with validated internal transcribed spacer (ITS) and/or large subunit (LSU) ribosomal DNA sequencing results. Expanding the mass spectrum database by increasing the number of reference strains for closely related species, including those of nonclinical origin, should enhance the usefulness of MALDI-TOF MS-based diagnostic analysis of these arthroconidial fungi in medical and other laboratories

The MIC range, MIC₅₀, MIC₉₀, and geometric mean for all 493 <i>C. neoformans</i> isolates for seven antifungals according to clinical and environmental origin of isolates.

<p>The MIC range, MIC₅₀, MIC₉₀, and geometric mean for all 493 <i>C. neoformans</i> isolates for seven antifungals according to clinical and environmental origin of isolates.</p