- A Rare Presentation of Cryptococcal Meningitis and Cerebellitis in an Asplenic Patient, Seronegative for Human Immunodeficiency Virus (HIV). [Journal Article]
- AJAm J Case Rep 2018 Feb 19; 19:183-186
- CONCLUSIONS: The occurrence of meningeal and cerebellar cryptococcosis in an asplenic patient is rare, and few cases have been previously reported. This case report highlights the possibility of invasive cryptococcal infection, or cryptococcosis, in asplenic individuals in the absence of HIV infection.
- Disseminated cryptococcosis presenting initially as lower limb cellulitis in a renal transplant recipient - a case report. [Journal Article]
- BNBMC Nephrol 2018 01 27; 19(1):18
- CONCLUSIONS: This case suggests that cutaneous cryptococcosis in immunosuppressed patients warrants a low threshold for investigation for disseminated disease even in the absence of other symptoms or signs.
- Epidemiological trends of cryptococcosis in Italy: Molecular typing and susceptibility pattern of Cryptococcus neoformans isolates collected during a 20-year period. [Journal Article]
- MMMed Mycol 2018 Jan 23
- In the present study clinical data and isolates from cases of cryptococcosis recorded during clinical surveys carried out in Italy from 1997 to 2016, were investigated. Molecular typing and antifunga...
In the present study clinical data and isolates from cases of cryptococcosis recorded during clinical surveys carried out in Italy from 1997 to 2016, were investigated. Molecular typing and antifungal susceptibility testing were performed in order to delineate the epidemiological trend of cryptococcosis in Italy and to define wild-type population for four different antifungal compounds. During the studied period, a total of 302 cases collected from 32 centers of 11 Italian regions were recorded. Analysis of clinical data showed a significant increase of frequency (from 7% to 38%) of cryptococcosis in human immunodeficiency virus (HIV)-negative patients primarily with hematologic malignancies and solid organ transplantations. The prevalence of the molecular types has significantly changed during the study period, showing an increase of VNIII isolates from 11% to 41% in HIV-negative patients, and a decrease of VNIV isolates from 36% to 16%. Antifungal susceptibility testing allowed us to calculate the epidemiological cut-off for flucytosine (1 mg/l), fluconazole (8 mg/l), itraconazole (0.5 mg/l), and voriconazole (0.25 mg/l). Most of the isolates were wild-type strains. Comparison of the MIC distributions according to molecular types showed that VNIV isolates had lower MICs for fluconazole and itraconazole than the VNI and VIII isolates. The current study emphasizes that the epidemiology of cryptococcosis in Italy has significantly changed over the last decades.
- HIV-Associated Cryptococcal Disease in Resource-Limited Settings: A Case for "Prevention Is Better Than Cure"? [Review]
- JFJ Fungi (Basel) 2017 Dec 02; 3(4)
- Cryptococcal disease remains a significant source of global morbidity and mortality for people living with HIV, especially in resource-limited settings. The recently updated estimate of cryptococcal ...
Cryptococcal disease remains a significant source of global morbidity and mortality for people living with HIV, especially in resource-limited settings. The recently updated estimate of cryptococcal disease revealed a global incidence of 223,100 cases annually with 73% of these cases being diagnosed in sub-Saharan Africa. Furthermore, 75% of the estimated 181,100 deaths associated with cryptococcal disease occur in sub-Saharan Africa. Point-of-care diagnostic assays have revolutionised the diagnosis of this deadly opportunistic infection. The theory of asymptomatic cryptococcal antigenaemia as a forerunner to symptomatic meningitis and death has been conclusively proven. Thus, cryptococcal antigenaemia screening coupled with pre-emptive antifungal therapy has been demonstrated as a cost-effective strategy with survival benefits and has been incorporated into HIV national guidelines in several countries. However, this is yet to be implemented in a number of other high HIV burden countries. Flucytosine-based combination therapy during the induction phase is associated with improved survival, faster cerebrospinal fluid sterilisation and fewer relapses. Flucytosine, however, is unavailable in many parts of the world. Studies are ongoing on the efficacy of shorter regimens of amphotericin B. Early diagnosis, proactive antifungal therapy with concurrent management of raised intracranial pressure creates the potential to markedly reduce mortality associated with this disease.
- Multilocus Sequence Typing Reveals both Shared and Unique Genotypes of Cryptococcus neoformans in Jiangxi Province, China. [Journal Article]
- SRSci Rep 2018 Jan 24; 8(1):1495
- 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 C...
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, fluconazole, itraconazole, and voriconazole), obvious differences in their minimum inhibitory concentrations were observed, even among isolates of the same ST. Our results suggest that continuous monitoring should be conducted to understand the changing dynamics of C. neoformans in this and other regions.
- Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance. [Journal Article]
- JVJ Vis Exp 2017 Dec 28; (130)
- Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations is essential, as resistance detected in vitr...
Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations is essential, as resistance detected in vitro can often be correlated with clinical failure. We examined the feasibility of using whole genome sequencing (WGS) for genome-wide analysis of antifungal drug resistance in C. glabrata. The aim was torecognize enablers and barriers in the implementation WGS and measure its effectiveness. This paper outlines the key quality control checkpoints and essential components of WGS methodology to investigate genetic markers associated with reduced susceptibility to antifungal agents. It also estimates the accuracy of data analysis and turn-around-time of testing. Phenotypic susceptibility of 12 clinical, and one ATCC strain of C. glabrata was determined through antifungal susceptibility testing. These included three isolate pairs, from three patients, that developed rise in drug minimum inhibitory concentrations. In two pairs, the second isolate of each pair developed resistance to echinocandins. The second isolate of the third pair developed resistance to 5-flucytosine. The remaining comprised of susceptible and azole resistant isolates. Single nucleotide polymorphisms (SNPs) in genes linked to echinocandin, azole and 5-flucytosine resistance were confirmed in resistant isolates through WGS using the next generation sequencing. Non-synonymous SNPs in antifungal resistance genes such as FKS1, FKS2, CgPDR1, CgCDR1 and FCY2 were identified. Overall, an average of 98% of the WGS reads of C. glabrata isolates mapped to the reference genome with about 75-fold read depth coverage. The turnaround time and cost were comparable to Sanger sequencing. In conclusion, WGS of C. glabrata was feasible in revealing clinically significant gene mutations involved in resistance to different antifungal drug classes without the need for multiple PCR/DNA sequencing reactions. This represents a positive step towards establishing WGS capability in the clinical laboratory for simultaneous detection of antifungal resistance conferring substitutions.
- Acanthamoeba endophthalmitis during treatment for cutaneous disease in a renal transplant patient. [Case Reports]
- TITranspl Infect Dis 2018 Jan 23
- Acanthamoeba infections are difficult to diagnose and treat. We present a renal transplant patient who developed Acanthamoeba endophthalmitis on therapy with posaconazole and miltefosine for cutaneou...
Acanthamoeba infections are difficult to diagnose and treat. We present a renal transplant patient who developed Acanthamoeba endophthalmitis on therapy with posaconazole and miltefosine for cutaneous acanthamobiasis. The patient was maintained on intracameral voriconazole injections, and oral azithromycin, fluconazole, and flucytosine. This case highlights novel presentations and treatments for acanthamoebic infection.
- Enhanced fluconazole consolidation therapy for cryptococcal meningitis in sub-Saharan Africa: Much to gain, little to lose. [Journal Article]
- ARAIDS Res Hum Retroviruses 2018 Jan 21
- Cryptococcal meningitis accounts for an estimated 25% of acquired immunodeficiency syndrome (AIDS)-associated mortality in sub-Saharan Africa. Accumulating animal and accumulating human evidence sugg...
Cryptococcal meningitis accounts for an estimated 25% of acquired immunodeficiency syndrome (AIDS)-associated mortality in sub-Saharan Africa. Accumulating animal and accumulating human evidence suggest that a higher, more fungicidal, dose of fluconazole during consolidation therapy could be more effective in controlling residual infection and may help significantly reduce post-hospitalization mortality. Although the potential for toxicity is low, the use of fluconazole at a dose of 800 mg/day during consolidation therapy requires examination in a randomized clinical trial. In the interim, within countries where post-discharge mortality from cryptococcal meningitis is high and amphotericin-flucytosine combination therapy remains unavailable, the use of high-dose fluconazole consolidation therapy deserves serious consideration as a strategy with limited risk and the potential for considerable public health benefit.
- Multicentric Cryptococcosis in a Congo African Grey Parrot ( Psittacus erithacus erithacus). [Journal Article]
- JAJ Avian Med Surg 2017; 31(4):373-381
- An approximately 10-year-old, female Congo African grey parrot ( Psittacus erithacus erithacus) developed progressive, unilateral exophthalmos and buphthalmos. Survey radiographs revealed a large, co...
An approximately 10-year-old, female Congo African grey parrot ( Psittacus erithacus erithacus) developed progressive, unilateral exophthalmos and buphthalmos. Survey radiographs revealed a large, coelomic, soft tissue mass, which was confirmed on computed tomography scan. Aspirates of both the contents of the buphthalmic globe and coelomic mass were consistent with Cryptococcus species. Initial results were later confirmed with serum antigen latex agglutination and polymerase chain reaction testing, and the organism was then identified as Cryptococcus neoformans with DNA sequencing. During the course of 1 year, the bird was treated with combinations of oral terbinafine, fluconazole, and flucytosine, as well as intraocular amphotericin B. The coelomic mass dramatically decreased in size during the course of treatment, but the globe continued to enlarge. The bird died after exhibiting ataxia and seizures approximately 13 months after initial diagnosis, and necropsy confirmed colonization of the cerebrum and meninges with Cryptococcus. Cryptococcus remains a rare fungal disease of birds that is often refractory to treatment.
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- A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009-17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. [Journal Article]
- JAJ Antimicrob Chemother 2018 Jan 09
- CONCLUSIONS: Overall, 25% and 13% of isolates were MDR and multi-azole resistant, respectively. The most common resistance combination was azoles and 5-flucytosine in 14% followed by azoles and amphotericin B in 7% and azoles and echinocandins in 2% of isolates.