Prevalence of the VNIc genotype of Cryptococcus neoformans in non-HIV-associated cryptococcosis in the Republic of Korea: Molecular epidemiology of cryptococcosis in Korea (original) (raw)
Related papers
FEMS Yeast Research, 2010
PCR fingerprinting and Multilocus Sequence Typing (MLST) was applied to determine the major molecular types of the C. neoformans/C. gattii species complex in the Republic of Korea. Of the 78 strains isolated from patients diagnosed with cryptococcosis between 1990 and 2008, 96% were C. neoformans serotype A, mating type MATα, and molecular type VNI. The remaining 4 % were C. gattii, serotype B, mating type MATα, and being either molecular type VGIIb or VGIII.
PLoS Neglected Tropical Diseases, 2013
To gain a more detailed picture of cryptococcosis in Thailand, a retrospective study of 498 C. neoformans and C. gattii isolates has been conducted. Among these, 386, 83 and 29 strains were from clinical, environmental and veterinary sources, respectively. A total of 485 C. neoformans and 13 C. gattii strains were studied. The majority of the strains (68.9%) were isolated from males (mean age of 37.97 years), 88.5% of C. neoformans and only 37.5% of C. gattii strains were from HIV patients. URA5-RFLP and/or M13 PCR-fingerprinting analysis revealed that the majority of the isolates were C. neoformans molecular type VNI regardless of their sources (94.8%; 94.6% of the clinical, 98.8% of the environmental and 86.2% of the veterinary isolates). In addition, the molecular types VNII (2.4%; 66.7% of the clinical and 33.3% of the veterinary isolates), VNIV (0.2%; 100% environmental isolate), VGI (0.2%; 100% clinical isolate) and VGII (2.4%; 100% clinical isolates) were found less frequently. Multilocus Sequence Type (MLST) analysis using the ISHAM consensus MLST scheme for the C. neoformans/ C. gattii species complex identified a total of 20 sequence types (ST) in Thailand combining current and previous data. The Thai isolates are an integrated part of the global cryptococcal population genetic structure, with ST30 for C. gattii and ST82, ST83, ST137, ST141, ST172 and ST173 for C. neoformans being unique to Thailand. Most of the C. gattii isolates were ST7 = VGIIb, which is identical to the less virulent minor Vancouver island outbreak genotype, indicating Thailand as a stepping stone in the global spread of this outbreak strain. The current study revealed a greater genetic diversity and a wider range of major molecular types being present amongst Thai cryptococcal isolates than previously reported.
Siriraj Medical Journal, 2019
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 I 2 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.
PLoS ONE, 2013
Background: Among members of Cryptococcus neoformans-Cryptococcus gattii species complex, C. neoformans is distributed worldwide whereas C. gattii is considered to be more prevalent in the subtropics and tropics including Taiwan. This nationwide study was undertaken to determine the distribution of genotypes, clinical characteristics and outcomes of 219 patients with proven cryptococcosis at 20 hospitals representative of all geographic areas in Taiwan during 1997-2010. Methods and Findings: Of 219 isolates analyzed, C. neoformans accounted for 210 isolates (95.9%); nine isolates were C. gattii (4.1%). The predominant genotype was VNI (206 isolates). The other genotypes included VNII (4 isolates), VGI (3 isolates) and VGII (6 isolates). Antifungal minimal inhibition concentrations higher than epidemiologic cutoff values (ECVs) were found in nine VNI isolates (7 for amphotericin B). HIV infection was the most common underlying condition (54/219, 24.6%). Among HIV-negative patients, liver diseases (HBV carrier or cirrhosis) were common (30.2%) and 15.4% did not have any underlying condition. Meningoencephalitis was the most common presentation (58.9%), followed by pulmonary infection (19.6%) and ''others'' (predominantly cryptococcemia) (18.7%). The independent risk factors for 10-week mortality, by multivariate analysis, were cirrhosis of liver (P = 0.014) and CSF cryptococcal antigen titer 512(P=0.020).Allexceptoneof54HIV−infectedpatientswereinfectedbyVNIgenotype(98.1512 (P = 0.020). All except one of 54 HIV-infected patients were infected by VNI genotype (98.1%). Of the 13 isolates of genotypes other than VNI, 12 (92.3%) were isolated from HIV-negative patients. HIV-infected patients compared to HIV-negative patients were more likely to have meningoencephalitis and serum cryptococcal antigen 512(P=0.020).Allexceptoneof54HIV−infectedpatientswereinfectedbyVNIgenotype(98.11:512. Patients infected with C. gattii compared to C. neoformans were younger, more likely to have meningoencephalitis (100% vs. 57%), reside in Central Taiwan (56% vs. 31%), and higher 10-week crude mortality (44.4% vs. 22.2%). Conclusions: Cryptococcus neoformans in Taiwan, more prevalent than C. gatii, has a predominant VNI genotype. Isolates with antifungal MIC higher than ECVs were rare.
Scientific reports, 2018
Cryptococcosis is a globally distributed infectious fungal disease. However, much remains unknown about its molecular epidemiology in many parts of the world. In this study, we analyzed 86 clinical Cryptococcus neoformans isolates from 14 regions in Jiangxi Province in south central China. Each isolate was from a different patient and 35 of the 86 (40.7%) patients were infected with HIV. All strains belonged to serotype A and mating type α (MATα). Genotyping based on DNA sequences at seven nuclear loci revealed eight sequence types (STs) among the 86 isolates, including two novel STs that have not been reported from other parts of the world. ST5 was the dominant genotype and our comparative analyses showed that these genotypes in Jiangxi likely originated by dispersal from other regions within and outside of China and/or mutations from another genotype within Jiangxi. Though none of the isolates was resistant to the five tested antifungal drugs (flucytosine, amphotericin B, fluconaz...
2014
Cryptococcus neoformans is a basidiomycetous encapsulated yeast with worldwide distribution. After inhalation from environmental sources, this pathogen may result in life-threatening infections in humans commonly affecting the central nervous system or respiratory system. 1 C. neoformans was previously subclassified into three varieties based upon biochemical differences and into four nonhybrid serotypes according to capsular agglutination reactions: 20 C. neoformans var. grubii (serotype A), C. neoformans var. neoformans 21 (serotype D), and C. neoformans var. gattii (serotype B and C). 2,3 22 C. neoformans is the commonest cause of fungal meningitis 23 worldwide. 4,5 C. neoformans var. grubii is an opportunistic pathogen 24 of immunocompromised patients, with HIV infection, corticosteroid 25 therapy, haematological malignancies, and solid-organ transplan-26 tation identified as major risk factors. 6,7 Cryptococcal meningitis is 27 the fourth most common opportunistic infection in patients with 28 HIV, with an estimated one million HIV-associated cryptococcosis 29 cases diagnosed annually worldwide. 5 In Southeast Asia, cryptococ-30 cosis is common amongst HIV-infected individuals, with an 31 estimated 120 cases per 1000 HIV-infected individuals per year. 4 32 The growing size of the immunocompromised patient population 33 from treatment with chemotherapy and biological agents will likely 34 further contribute to the medical importance of cryptococcosis. 6
Cryptococcus neoformans Strains and Infection in Apparently Immunocompetent Patients, China
Emerging Infectious Diseases, 2008
To determine the population structure of the cryptococcosis agents in China, we analyzed the genotype of 120 Cryptococcus neoformans and 9 Cryptococcus gattii strains isolated from 1980 through 2006 from cryptococcosis patients residing in 16 provinces of mainland China. A total of 71% (91/129) of the clinical strains isolated from 1985 through 2006 were from patients without any apparent risk factors. Only 8.5% (11/129) were from AIDS patients; the remaining 20.5% (27/129) were from patients with underlying diseases other than HIV infection. One hundred twenty of the 129 isolates were C. neoformans serotype A, mating type MATα strains that exhibited an identical M13-based VNI subtype, which was distinguishable from the reference VNI molecular type. The 9 remaining isolates were serotype B, MATα strains of C. gattii and portrayed a typical VGI molecular type. Data analyzed from multilocus sequences showed no variation and that these Chinese C. neoformans isolates belong to a cluster that has phylogenetically diverged from the VNI reference strain. Our fi nding that most cryptococcosis patients in China had no apparent risk factor is in stark contrast with reports from other countries.
Medical Mycology, 2004
A high biodiversity of Cryptococcus neoformans isolates is known to exist in some Brazilian urban areas, raising the possibility that patients may encounter multiple inoculum sources in their daily life. C. neoformans isolates from two groups of AIDS patients with cryptococcosis from Rio de Janeiro were studied by polymerase chain reaction (PCR) fingerprinting and randomly amplified polymorphic DNA (RAPD) analysis. The first group contained 60 serial isolates obtained from 19 patients over periods ranging from 18 to 461 days; the intent was to determine whether the original strain persisted or whether reinfection with a new strain occurred. The second group was made up of 22 isolates from 11 patients, and consisted of a pair of isolates collected from blood and cerebrospinal fluid from each patient either before or shortly after treatment was initiated. The aim was to determine if the patient was infected by different strains simultaneously. All isolates were subtyped by PCR fingerprinting, using minisatellite (M13), and microsatellite [(GACA) 4 and (GTG) 5 ] specific primers, and RAPD analysis employing the combined primers 5SOR and CN1. The majority of isolates were C. neoformans var. grubii, specifically, molecular types VNI or VNII, but numerous distinguishable subtypes were found. Only three isolates were C. n. var. gattii (molecular types VGI or VGII). Except in two cases, all isolates obtained from the same patient showed identical PCR profiles independent of time of isolation or body site. Almost all patients, however, carried unique genotypes not found in any other patient. Our results confirm that persistent cryptococcal infection is caused by relapse rather than reinfection, but they also show that in exceptional cases, patients may be infected with more than one C. neoformans strain.
Journal of Infectious Diseases, 1996
Sixty clinical isolates of Cryptococcus neoformans var. neoformans were analyzed by random amplification of polymorphicDNA (RAPD) using 12-to 22-mer primers in pairs. Fivemajor profiles, which clearly distinguished between serotypes A (profilesI-III), AD (profile IV), and D (profileV), were identified. Forty-two of 58 serotype A isolates were assigned to profile I, 13 to profile II, and 3 to profile III. Profile I comprised 5 subtypes (profiles la-Ie), with 37 of 42 isolates in profile Ia. Twenty-seven of 28 isolates from patients with AIDS belonged to profile Ia (P < .001), as did 7 of 10 isolates from otherwise immunocompromised patients. Isolates from immunocompetent hosts were broadly distributed (profile I, 8 isolates; profile II, 10 isolates; profile III, 2 isolates). RAPD profileswere independent of body site and geographic origin of isolates. Isolate pairs from 3 patients produced identical profiles. A predominant genetic profile among serotype A strains from AIDS patients has not been reported previously. Cryptococcus neoformans is an important opportunistic pathogen in patients with AIDS [1,2]. In addition, a significant proportion of infections occurs in immunocompetent hosts [3]. Two varieties of C. neoformans are recognized: C. neoformans var. neoformans (serotypes A, D, or AD) and C. neoformans var. gattii (serotypes B or C). These varieties differ in their ecology and epidemiology; the former is found in nature in avian excreta, whereas the latter has been associated with eucalyptus trees in Australia [2]. Immunosuppressed persons are nearly always infected with C. n. var. neoformans [1, 2]. In contrast, C. n. var. gattii has a propensity to cause disease in immunocompetent hosts [3]. Genetic differences among strains of cryptococci have been demonstrated by several methods, including electrophoretic karyotyping [4] and Southern blot hybridization with DNA probes based on repetitive DNA sequences from C. neoformans [5]. These techniques are time-consuming and not readily adaptable in the clinical laboratory for epidemiologic purposes. Recently, a method was developed to discriminate between strains of the same microorganism by amplifying polymorphic DNA with the polymerase chain reaction (PCR) using arbi