Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-8 (of 8 Records) |
Query Trace: Ahlquist A[original query] |
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Detection of fungal DNA in human body fluids and tissues during a multistate outbreak of fungal meningitis and other infections.
Gade L , Scheel CM , Pham CD , Lindsley MD , Iqbal N , Cleveland AA , Whitney AM , Lockhart SR , Brandt ME , Litvintseva AP . Eukaryot Cell 2013 12 (5) 677-83 Exserohilum rostratum was the major cause of an outbreak of fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak. |
Diagnosis of fungal opportunistic infections in people living with HIV from Guatemala and El Salvador
Forno D , Samayoa B , Medina N , Arathoon E , Mejia CR , Gordillo R , Cedillos R , Rodas J , Ahlquist Cleveland A , Chiller T , Caceres DH . Mycoses 2021 64 (12) 1563-1570 OBJECTIVES: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory tests, such as culture and microscopy are not optimal, however, antigen tests are rapid, highly sensitive, and specific for diagnosis of fungal opportunistic infections (OI). The aim of this study was to describe the results of a laboratory-based surveillance system for histoplasmosis and cryptococcosis. METHODS: An observational cross-sectional study based on laboratory surveillance, was carried out in two hospitals in Guatemala and one hospital in El Salvador, between July 2012 to and December 2014. Diagnosis of histoplasmosis and cryptococcosis in PLHIV were performed by culture and antigen test. RESULTS: A total of 160 PLHIV were diagnosed with fungal OI, of which, 96 (60%) were diagnosed with histoplasmosis, 62 (39%) were with cryptococcosis, and two patients (1%) were diagnosed with both fungal diseases. Of the 160 patients analyzed in this study, 94 (59%) were diagnosed using only an antigen assay. CD4 cell count data was available for 136 (85%) patients; 127 (93%) patients had a CD4 count <200 and 90 (66%) had counts <50 CD4 cells per µL. Antiretroviral therapy utilization at diagnosis was low (33%). Seventy-one out of 160 (44%) were co-infected with tuberculosis or other OIs. CONCLUSION: More than half of the patients in this study were diagnosed only by rapid laboratory antigen tests. A high percent of the patients had advanced HIV disease. |
Validation of a histoplasma ELISA antigenuria test in Colombian patients with AIDS for diagnosis and follow-up during therapy
Caceres DH , Scheel CM , Tobon AM , Ahlquist Cleveland A , Restrepo A , Brandt ME , Chiller T , Gomez BL . Clin Vaccine Immunol 2014 We validated an antigen capture ELISA test in Colombian persons with AIDS and proven histoplasmosis, and evaluated the correlation between antigenuria and clinical improvement during follow up. The sensitivity of the H. capsulatum ELISA was 86% and the overall specificity was 94%. The antigen test successfully monitored response to therapy. |
Species identification and antifungal susceptibility of Candida bloodstream isolates from population-based surveillance in two US cities: 2008-2011
Lockhart SR , Iqbal N , Ahlquist AM , Farley MM , Harrison LH , Bolden CB , Baughman W , Stein B , Hollick R , Park BJ , Chiller T . J Clin Microbiol 2012 50 (11) 3435-42 Between 2008 and 2011, population-based candidemia surveillance was conducted in Atlanta, GA and Baltimore, MD. Surveillance had been previously performed in Atlanta in 1992-1993 and in Baltimore in 1998-2000, making this the first population-based candidemia surveillance conducted over multiple time points in the US. From 2,675 identified cases of candidemia in the current surveillance, 2,329 Candida isolates were collected. Candida albicans no longer comprised the majority of isolates but remained the most frequently isolated species (38%), followed by C. glabrata (29%), C. parapsilosis (17%) and C. tropicalis (10%). The species distribution has changed over time; in both Atlanta and Baltimore the proportion of C. albicans decreased and the proportion of C. glabrata increased, while the proportion of C. parapsilosis increased in Baltimore only. There were 98 multi-species episodes, with C. albicans and C. glabrata the most frequently encountered combination. The new species-specific CLSI Candida MIC breakpoints were applied to these data. With the exception of C. glabrata (11.9% resistant), resistance to fluconazole was very low (2.3% for C. albicans, 6.2% for C.tropicalis and 4.1% for C. parapsilosis). There was no change in the proportion of fluconazole resistance between surveillance periods. Overall echinocandin resistance was low (1%) but was higher for C. glabrata isolates, ranging from 2.1% resistant to caspofungin in Baltimore to 3.1% resistant to anidulafungin in Atlanta. Given the increase at both sites and the higher echinocandin resistance, C. glabrata should be closely monitored in future surveillance. |
Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata
Pfaller MA , Castanheira M , Lockhart SR , Ahlquist AM , Messer SA , Jones RN . J Clin Microbiol 2012 50 (4) 1199-203 The echinocandin class of antifungal agents is considered to be the first-line treatment of bloodstream infections (BSI) due to Candida glabrata. Recent reports of BSI due to strains of C. glabrata resistant to both fluconazole and the echinocandins are of concern and prompted us to review the experience of two large surveillance programs, the SENTRY Antimicrobial Surveillance Program for the years 2006 through 2010 and the Centers for Disease Control and Prevention population-based surveillance conducted in 2008 to 2010. The in vitro susceptibilities of 1,669 BSI isolates of C. glabrata to fluconazole, voriconazole, anidulafungin, caspofungin, and micafungin were determined by CLSI broth microdilution methods. Fluconazole MICs of ≥64 mcg/ml were considered resistant. Strains for which anidulafungin and caspofungin MICs were ≥0.5 mcg/ml and for which micafungin MICs were ≥0.25 mcg/ml were considered resistant. A total of 162 isolates (9.7%) were resistant to fluconazole, of which 98.8% were nonsusceptible to voriconazole (MIC > 0.5 mcg/ml) and 9.3%, 9.3%, and 8.0% were resistant to anidulafungin, caspofungin, and micafungin, respectively. There were 18 fluconazole-resistant isolates that were resistant to one or more of the echinocandins (11.1% of all fluconazole-resistant isolates), all of which contained an acquired mutation in fks1 or fks2. By comparison, there were no echinocandin-resistant strains detected among 110 fluconazole-resistant isolates of C. glabrata tested in 2001 to 2004. These data document the broad emergence of coresistance over time to both azoles and echinocandins in clinical isolates of C. glabrata. |
Long-term follow-up and survival of antiretroviral-naive patients with cryptococcal meningitis in the pre-antiretroviral therapy era, Gauteng Province, South Africa
Park BJ , Shetty S , Ahlquist A , Greenbaum A , Miller JL , Motsi A , McCarthy K , Govender N . Int J STD AIDS 2011 22 (4) 199-203 Cryptococcal meningitis (CM) is a major cause of death among HIV-infected persons in sub-Saharan Africa. We conducted a study to describe the long-term outcomes during the pre-antiretroviral post-ART therapy period. Enrolled cases were those detected through population-based surveillance in Gauteng Province, South Africa, and diagnosed during March-November 2002 and July-September 2003 from eight large hospitals representing academic, provincial and rural settings. Of 1089 case-patients diagnosed with CM, 721 (70%) survived to discharge. Among the 256 with follow-up information, 154 (60%) were established to have died, 44% of whom died as outpatients. Overall, the 14- and 90-day survival post-diagnosis was 68% and 41%, respectively. On Cox proportional hazards multivariable analysis, severe disease was associated with shorter survival time; having received any antifungal treatment for the cryptococcal episode was associated with increased survival time at follow-up. Although most patients in this cohort survived the initial hospitalization, only 41% were still alive three months after diagnosis, with nearly half of deaths occurring outside a hospital. These data are an important baseline from which to measure effectiveness of public health management of CM in South Africa. |
FKS mutations and elevated echinocandin MIC values among Candida glabrata isolates from US population-based surveillance
Zimbeck AJ , Iqbal N , Ahlquist AM , Farley MM , Harrison LH , Chiller T , Lockhart SR . Antimicrob Agents Chemother 2010 54 (12) 5042-7 Candida glabrata is the second leading cause of candidemia in the United States. Its high resistance to triazole antifungal drugs has led to the increased use of the echinocandin class of antifungal agents for primary therapy of these infections. We monitored C. glabrata bloodstream isolates from a population-based surveillance for elevated echinocandin MIC values (MIC ≥0.25 mug/ml). From the 490 C. glabrata isolates that were screened, we identified 16 isolates with an elevated MIC value (2.9% of isolates from Atlanta and 2.0% of isolates from Baltimore) to one or more of the echinocandin drugs caspofungin, anidulafungin or micafungin. All the isolates with elevated MIC values had a mutation in the previously identified hotspot 1 of either glucan synthase FKS1 (n=2) or FKS2 (n=14) genes. No mutations were detected in hotspot 2 of either FKS1 or FKS2. The predominant mutation was FKS2 serine 663 to proline (S663P), found in 10 of the isolates with elevated echinocandin MICs. Two of the mutations, R631G in FKS1 and R665G in FKS2 have not been previously reported for C. glabrata. Multilocus sequence typing indicated that the predominance of the S663P mutation was not due to the clonal spread of a single sequence type. With a rising number of echinocandin therapy failures reported, it is important to continue to monitor rates of elevated echinocandin MIC values and the associated mutations. |
Correlation of genotype and in vitro susceptibilities of Cryptococcus gattii from the Pacific Northwest of the United States
Iqbal N , Debess EE , Wohrle R , Sun B , Nett RJ , Ahlquist AM , Chiller T , Lockhart SR , Cryptococcus gattii Public Health Working Group . J Clin Microbiol 2009 48 (2) 539-44 Cryptococcus gattii emerged in North America in 1999 as a human and veterinary pathogen on Vancouver Island, British Columbia. The emergent subtype, VGIIa, and the closely related subtype VGIIb can now be found in the US in Washington, Oregon, and California. We performed multilocus sequence typing and antifungal susceptibility testing on 43 isolates of C. gattii from human patients in Oregon, Washington, California and Idaho. In contrast to Vancouver Island, VGIIa was the most frequent but not the predominant subtype in the northwest US. Antifungal susceptibility testing showed statistically significant differences in minimum inhibitory concentration (MIC) values between the subtypes. This is the first study to apply antifungal susceptibility testing to C. gattii isolates from the Pacific Northwest and the first to make direct comparisons between subtypes. |
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