Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 65 Records) |
Query Trace: Chiller TM [original query] |
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Induction-phase treatment costs for cryptococcal meningitis in high HIV-burden African countries: New opportunities with lower costs
Larson B , Shroufi A , Muthoga C , Oladele R , Rajasingham R , Jordan A , Jarvis JN , Chiller TM , Govender NP . Wellcome Open Res 12/28/2021 6 140 Introduction: Access to and the cost of induction treatment for cryptococcal meningitis (CM) is rapidly changing. The newly-announced price for flucytosine ($0.75 per 500 mg pill) and possibly lower prices for liposomal amphotericin B (AmB-L) create opportunities to reduce CM treatment costs compared to the current standard treatment in low- and middle-income countries. Methods: We developed an Excel-based cost model to estimate health system treatment costs for CM over a two-week induction phase for multiple treatment combinations, newly feasible with improved access to flucytosine and AmB-L. CM treatment costs include medications, laboratory tests and other hospital-based costs (bed-day costs and healthcare worker time). We report results from applying the model using country-specific information for South Africa, Uganda, Nigeria, and Botswana. Results: A 14-day induction-phase of seven days of inpatient AmB-D with flucytosine, followed by seven days of high-dose fluconazole as an outpatient, will cost health systems less than a 14-day hospital stay with AmB-D and fluconazole. If daily AmB-L replaces AmB-D for those with baseline renal dysfunction, with a cost of $50 or less per 50 mg vial, incremental costs would still be less than the AmB-D with fluconazole regimen. Simple oral combinations (e.g., seven days of flucytosine with fluconazole as an inpatient) are practical when AmB-D is not available, and treatment costs would remain less than the current standard treatment. Conclusions: Improved access to and lower prices for flucytosine and AmB-L create opportunities for improving CM treatment regimens. An induction regimen of flucytosine and AmB-D for seven days is less costly than standard care in the settings studied here. As this regimen has also been shown to be more effective than current standard care, countries should prioritize scaling up flucytosine access. The cost of AmB-L based regimens is highly dependent on the price of AmB-L, which currently remains unclear. |
Emergence of zoonotic sporotrichosis in Brazil: a genomic epidemiology study
Ribeiro Dos Santos A , Misas E , Min B , Le N , Bagal UR , Parnell LA , Sexton DJ , Lockhart SR , de Souza Carvalho Melhem M , Takahashi JPF , Oliboni GM , Bonfieti LX , Cappellano P , Sampaio JLM , Araujo LS , Alves Filho HL , Venturini J , Chiller TM , Litvintseva AP , Chow NA . Lancet Microbe 2024 BACKGROUND: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology. METHODS: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates. FINDINGS: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade. INTERPRETATION: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil. |
Outbreak of fusarium solani meningitis in immunocompetent persons associated with neuraxial blockade in Durango, Mexico, 2022-2023
García-Rodríguez G , Duque-Molina C , Kondo-Padilla I , Zaragoza-Jiménez CA , González-Cortés VB , Flores-Antonio R , Villa-Reyes T , Vargas-Rubalcava A , Ruano-Calderon LÁ , Tinoco-Favila JC , Sánchez-Salazar HC , Rivas-Ruiz R , Castro-Escamilla O , Martínez-Gamboa RA , González-Lara F , López-Martínez I , Chiller TM , Pelayo R , Bonifaz LC , Robledo-Aburto Z , Alcocer-Varela J . Open Forum Infect Dis 2024 11 (2) ofad690 BACKGROUND: Fungal meningitis can be associated with epidural anesthesia procedures. Fusariosis is a rare infection typically affecting immunocompromised patients and rarely causes meningitis. During 2022-2023, public health officials responded to a large outbreak of Fusarium solani meningitis associated with epidural anesthesia in Durango, Mexico. METHODS: The public health response and epidemiological and clinical features of patients affected by this outbreak were described. Coordinated actions were addressed to identify the etiological agent, determine its drug susceptibility, develop diagnostic tests, and implement clinical and epidemiological protocols. Retrospective analyses of clinical variables and outcomes were performed to determine association with better patient survival. RESULTS: A total of 1801 persons exposed to epidural anesthesia were identified, of whom 80 developed meningitis. Fusarium solani was found in 3 brain biopsies and showed susceptibility to voriconazole and amphotericin B. After F solani polymerase chain reaction (PCR) implementation, 57 patients with meningitis were PCR-screened, and 31 (38.8%) had a positive result. Most patients were female (95%), and cesarean section was the most common surgical procedure (76.3%). The case fatality rate was 51.3% (41 patients) and the median hospitalization duration was 39.5 days (interquartile range, 18-86 days). Seventy-one patients (88.8%) received voriconazole/amphotericin B and 64 subjects (80%) additionally received steroids. Cox regression analysis showed an increased lethality risk in patients who received antifungal treatment after 5 days (hazard ratio, 2.1 [95% confidence interval, 1.01-4.48], P < .05). CONCLUSIONS: The F solani meningitis outbreak in Durango was an unprecedented medical challenge. Timely treatment and effective healthcare management were associated with better survival outcomes. |
Candida auris: a global pathogen that has taken root in Colombia
Escandón P , Lockhart SR , Chow NA , Chiller TM . Biomedica 2023 43 278-287 Candida auris has been recognized as an emerging multidrug-resistant pathogen with a significant public health burden, causing cases of invasive infection and colonization due to its persistence on inanimate surfaces, ability to colonize skin of some patients, and high transmissibility in healthcare settings. The first sporadic report of the isolation of this species from the ear canal of a patient in Asia was in 2009 and reports from other regions of the world soon followed. However, it was not until 2015 that global epidemiological alerts were communicated as a result of an increasing number of reports of invasive infections caused by C. auris in several countries. Colombia was soon added to this list in 2016 after an unusual increase in the number of C. haemulonii isolates was reported, later confirmed as C. auris. Since the issuing of a national alert by the Colombian National Institute of Health together with the Ministry of Health in 2016, the number of cases reported reached over 2,000 by 2022. Colombian isolates have not shown pan resistance to available antifungals, unlike C. auris strains reported in other regions of the world, which leaves patients in Colombia with therapeutic options for these infections. However, increasing fluconazole resistance is being observed. Whole-genome sequencing of Colombian C. auris isolates has enhanced molecular epidemiological data, grouping Colombian isolates in clade IV together with other South American isolates. |
A multicenter survey of asymptomatic cryptococcal antigenemia among patients with advanced HIV disease in Nigeria
Oladele RO , Jordan AM , Okaa JU , Osaigbovo II , Shettima SA , Shehu NY , Davies AA , Mohammed Y , Alex-Wele MA , Iliyasu G , Nwaokenye JC , Fayemiwo SA , Udoh UA , Gbajabiamila T , Denning DW , Chiller TM . PLOS Glob Public Health 2023 3 (1) e0001313 As of 2018, cryptococcal antigen (CrAg) screening in patients with advanced human immunodeficiency virus (HIV) disease (AHD) was not routinely implemented in Nigeria despite being recommended in the national HIV treatment guidelines. Our aim was to determine the prevalence and risk factors for asymptomatic cryptococcal antigenemia in adult people living with HIV (PLHIV) in Nigeria to advocate for the implementation of routine CrAg screening. A descriptive cross-sectional study and CrAg screening of consecutive adult PLHIV with CD4 counts ≤200 cells/μL was conducted from April 2018 to April 2019 at HIV clinics in eleven tertiary hospitals spread across Nigeria's six geopolitical regions. Prevalence of asymptomatic cryptococcal antigenemia was estimated by facility and geopolitical zone. Logistic regression was conducted to identify risk factors for cryptococcal antigenemia. In total, 1,114 patients with AHD were screened. The overall prevalence of asymptomatic cryptococcal antigenemia was 3.9% with wide variation across facilities (range: 0/75 [0%]- 15/122 [12.3%]) and geopolitical zones (range: 0/75 [0%]-19/279 [6.8%]). Prevalence of antigenemia was highest in the South-West (19/279 [6.8%]) and lowest in the North-East (0/75 [0%]). Prevalence was 5.2% (26/512) and 3.2% (18/561) in patients with CD4<100 and CD4 of 101-200, respectively. Of all patients with antigenemia, 50% were on antiretroviral therapy (ART) at the time of having a positive CrAg test. In adjusted analysis, cryptococcal antigenemia was significantly less in patients on ART and patients who had completed any formal education. The survey showed a high overall burden of cryptococcal antigenemia in Nigeria, with variable prevalence across geopolitical regions. We provided valuable evidence for implementing routine CrAg screening of AHD patients in Nigeria which has commenced in selected centres. |
Invasive mold infections following Hurricane Harvey-Houston, Texas
Toda M , Williams S , Jackson BR , Wurster S , Serpa JA , Nigo M , Grimes CZ , Atmar RL , Chiller TM , Ostrosky-Zeichner L , Kontoyiannis DP . Open Forum Infect Dis 2023 10 (3) ofad093 BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making. METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status. RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 cases) (rate ratio, 1.48 [95% confidence interval, 1.10-2.00]), largely driven by surveillance IMI cases. Aspergillus was the most common species cultured (33.5% prehurricane and 39.9% posthurricane). About one-quarter (25.8%) of IMI patients lacked classical IMI risk factors such as hematologic malignancy and transplantations. Overall, 45.1% of IMI patients received intensive care, and in-hospital all-cause mortality was 24.2%. CONCLUSIONS: IMI incidence likely increased following Hurricane Harvey and outcomes for IMI patients were severe. Patient and clinician education on IMI prevention and identification is warranted, particularly as the frequency of extreme weather events increases due to climate change. |
Genomic description of human clinical Aspergillus fumigatus isolates, California, 2020.
Misas E , Deng JZ , Gold JAW , Gade L , Nunnally NS , Georgacopoulos O , Bentz M , Berkow EL , Litvintseva AP , Chiller TM , Klausner JD , Chow NA . Med Mycol 2023 61 (2) Aspergillus fumigatus, an environmental mold, causes life-threatening infections. Studies on the phylogenetic structure of human clinical A. fumigatus isolates are limited. Here, we performed whole-genome sequencing of 24 A. fumigatus isolates collected from 18 patients in U.S. healthcare facilities in California. Single-nucleotide polymorphism (SNP) differences between patient isolates ranged from 187-70 829 SNPs. For five patients with multiple isolates, we calculated the within-host diversities. Three patients had a within-host diversity that ranged from 4-10 SNPs and two patients ranged from 2-16 977 SNPs. Findings revealed highly diverse A. fumigatus strains among patients and two patterns of diversity for isolates that come from the same patient, low and extremely high diversity. | Aspergillus fumigatus is an environmental mold. It can cause a severe infection called aspergillosis in patients with weakened immune systems. We analyzed A. fumigatus DNA from patients at California hospitals. We described genetic diversity between samples from the same patients and among different patients. Our findings provide insight on using genomic sequencing to investigate aspergillosis in hospitals. | eng |
Endemic mycoses: Underdiagnosed and underreported
Thompson GR3rd , Chiller TM . Ann Intern Med 2022 175 (12) 1759-1760 Blastomycosis, coccidioidomycosis, and histoplasmosis are the endemic mycoses that are most prevalent in North America. Exposure within the focal endemic regions is often unavoidable, and patients are frequently unaware of activities that increase individual risk. These fungi have traditionally had distinct geographic distributions, although these regions are expanding and the organisms are probably much more widespread. They occupy a specific ecological niche in the environment and are able to cause disease in healthy hosts. After the infectious “spores” are inhaled, these fungal pathogens often survive macrophage ingestion and escape, thereafter replicating and producing clinical illness. |
An updated systematic review of HIV-associated cryptococcal meningitis treatment strategies
Shapiro AE , Tenforde MW , Chiller TM , Ford N , Rajasingham R . HIV Med 2022 24 (4) 507-512 BACKGROUND: The purpose of this systematic review is to provide updated evidence on the preferred induction therapy for the treatment of HIV-associated cryptococcal meningitis considering the most recent evidence available in order to inform the need for updates to WHO guidelines. METHODS: We searched Medline via PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for published or completed randomized clinical trials that evaluated induction treatment of first episode HIV-associated cryptococcal meningitis from 9 July 2018 (date of last search) to 1 September 2021. RESULTS: One randomized clinical trial of 844 people with HIV-associated cryptococcal meningitis met the inclusion criteria. Participants were randomized to: (1) amphotericin deoxycholate for 7 days, with flucytosine and fluconazole (control); or (2) a single dose of liposomal amphotericin 10 mg/kg with flucytosine and fluconazole (intervention). In the intention-to-treat analysis, 10-week mortality was 24.8% [95% confidence interval (CI): 20.7-29.3%] in the single-dose liposomal amphotericin group compared with 28.7% (95% CI: 24.4-33.4%) in the control group. The absolute difference in 10-week mortality was -3.9% with an upper one-sided 95% CI of 1.2%, within the 10% pre-specified non-inferiority margin. Fewer participants had grade 3 and 4 adverse events in the intervention arm compared with the control arm (50.0% vs. 62.3%, p < 0.001). CONCLUSIONS: In the single study included in this systematic review, single high-dose liposomal amphotericin B with flucytosine and fluconazole was non-inferior to the WHO-recommended standard of care induction therapy for HIV-associated cryptococcal meningitis, with significantly fewer adverse events. |
The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis
Rajasingham R , Govender NP , Jordan A , Loyse A , Shroufi A , Denning DW , Meya DB , Chiller TM , Boulware DR . Lancet Infect Dis 2022 22 (12) 1748-1755 BACKGROUND: Cryptococcal meningitis is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. The estimates of national, regional, and global burden of cryptococcal meningitis are essential to guide prevention strategies and determine needs for diagnostic tests and treatments. We present a 2020 estimate of the global burden of HIV-associated cryptococcal infection (antigenaemia), cryptococcal meningitis, and cryptococcal-associated deaths. METHODS: We defined advanced HIV disease as adults with a CD4 count of less than 200 cells/μL, as this group is at highest risk for cryptococcosis. We used UNAIDS estimates (2019-20) and population-based HIV impact assessment surveys (2016-18) to estimate the number of adults with CD4 counts of less than 200 cells/μL at risk for cryptococcosis, by country and region. Secondly, we summarised cryptococcal antigenaemia prevalence in those with a CD4 count of less than 200 cells/μL by reviewing published literature. Thereafter, we calculated the number of cryptococcal antigen (CrAg)-positive people in each country and region by multiplying the number with advanced HIV disease at risk for cryptococcal infection by the cryptococcal antigenaemia prevalence of the respective country or region. We estimated progression from cryptococcal antigenaemia to meningitis or death based on estimates from the published literature. FINDINGS: We estimated that there were 4·3 million (IQR 3·0-4·8) adults with HIV and CD4 counts of less than 200 cells/μL globally in 2020. We calculated a mean global cryptococcal antigenaemia prevalence of 4·4% (95% CI 1·6-7·4) among HIV-positive people with CD4 counts of less than 200 cells/μL, corresponding to 179 000 cases (IQR 133 000-219 000) of cryptococcal antigenaemia globally in 2020. Annually, we estimated that there are 152 000 cases (111 000-185 000) of cryptococcal meningitis, resulting in 112 000 cryptococcal-related deaths (79 000-134 000). Globally, cryptococcal disease accounts for 19% (13-24) of AIDS-related mortality. INTERPRETATION: Despite a reduction in the estimated absolute global burden of HIV-associated cryptococcal meningitis compared with 2014, likely to be due to antiretroviral therapy expansion, cryptococcal disease still accounts for 19% of AIDS-related deaths, similar to 2014 estimates. To end cryptococcal meningitis deaths by 2030, cryptococcal diagnostics, meningitis treatments, and implementation of preventive screening are urgently needed. FUNDING: None. |
Invasive mould infections in patients from floodwater- damaged areas after Hurricane Harvey - a closer look at an immunocompromised cancer patient population
Wurster S , Paraskevopoulos T , Toda M , Jiang Y , Tarrand JJ , Williams S , Chiller TM , Jackson BR , Kontoyiannis DP . J Infect 2022 84 (5) 701-709 OBJECTIVES: Extensive floodwater damage following hurricane Harvey raised concerns of increase in invasive mould infections (IMIs), especially in immunocompromised patients. To more comprehensively characterize the IMI landscape pre- and post- Harvey, we used a modified, less restrictive clinical IMI (mcIMI) definition by incorporating therapeutic-intent antifungal drug prescriptions combined with an expanded list of host and clinical features. METHODS: We reviewed 103 patients at MD Anderson Cancer Center (Houston, Texas), who lived in Harvey-affected counties and had mould-positive cultures within 12 months pre-/post-Harvey (36 and 67 patients, respectively). Cases were classified as proven or probable IMI (EORTC/MSG criteria), mcIMI, or colonization/ contamination. We also compared in-hospital mortality and 42- day survival outcomes of patients with mcIMI pre-/ post- Harvey. RESULTS: The number of patients with mould- positive cultures from Harvey- affected counties almost doubled from 36 pre- Harvey to 67 post- Harvey (p < 0.01). In contrast, no significant changes in (mc) IMI incidence post- Harvey nor changes in the etiological mould genera were noted. However, patients with mcIMIs from flood affected areas had significantly higher in- hospital mortality (p = 0.01). CONCLUSIONS: We observed increased colonization but no excess cases of (mc)IMIs in immunosuppressed cancer patients from affected areas following a large flooding event such as hurricane Harvey. |
Evaluation of OIDx Histoplasma Urinary Antigen EIA
Cáceres DH , Gómez BL , Tobón Á M , Chiller TM , Lindsley MD . Mycopathologia 2021 187 (1) 129-131 A sandwich enzyme immunoassay (EIA) for the detection of Histoplasma antigens (Ag) in urine, developed by Optimum Imaging Diagnostics (OIDx) was evaluated. A verification using a standardized reference panel of urine samples found sensitivity of 92%, specificity of 32% and accuracy of 51%. In this study, the OIDx Histoplasma urinary Ag EIA displayed high sensitivity, however, in non-histoplasmosis cases this EIA displayed false-positive results in 68% of specimens tested. |
Ventilator-associated pneumonia involving
Fernandez NB , Caceres DH , Beer KD , Irrazabal C , Delgado G , Farias L , Chiller TM , Verweij PE , Stecher D . Med Mycol Case Rep 2021 31 19-23 Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, emerged in Wuhan, China, in December 2019 and rapidly spread around the world. Invasive aspergillosis has been reported as a complication of severe influenza pneumonia among intensive care patients. Similarities between COVID-19 and influenza pneumonia, together with limited published case series, suggest that aspergillosis may be an important complication of COVID-19. This report describes a case of ventilator-associated pneumonia involving Aspergillus flavus in a patient with COVID-19 from Buenos Aires, Argentina. |
Patient notification about suspected hospital-associated outbreaks of invasive mold infections: Considerations for public health and hospital personnel
Gandhi P , Benedict K , Toda M , Beer KD , Chiller TM , Jackson BR . Infect Control Hosp Epidemiol 2021 42 (7) 1-6 A common type of fungal disease investigation involves hospital-associated clusters of invasive mold infections (IMIs), which typically occur among immunocompromised patients. Responding to IMI clusters can be challenging for public health and hospital personnel for several reasons such as difficulty of confirming the existence of an outbreak, difficulty of determining source. Although many resources exist to guide patient notification about healthcare incidents (eg, bloodborne exposures, disease outbreaks), IMI clusters involve special considerations related to the complex diseases, uncertain exposures, and differential benefits and risks of notification. Early, nuanced communication about hospital-associated IMI clusters is almost always the best course of action to help reduce risks to patients' health and foster trust between patients and hospitals. |
Recent Trends in the Epidemiology of Fungal Infections
Seagle EE , Williams SL , Chiller TM . Infect Dis Clin North Am 2021 35 (2) 237-260 The breadth of fungi causing human disease and the spectrum of clinical presentations associated with these infections has widened. Epidemiologic trends display dramatic shifts with expanding geographic ranges, identification of new at-risk groups, increasing prevalence of resistant infections, and emergence of novel multidrug-resistant pathogenic fungi. Certain fungi have been transmitted between patients in clinical settings. Major health events not typically associated with mycoses resulted in larger proportions of the population susceptible to secondary fungal infections. Many health care-related, environmental, and socioeconomic factors have influenced these epidemiologic shifts. This review summarizes updates to clinically significant fungal pathogens in North America. |
Implementation of Rapid Diagnostics Assays for Detection of Histoplasmosis and Cryptococcosis in Central American People Living with HIV
Caceres DH , Arauz AB , Flores C , Santiago E , Montoya S , Saenz C , Torres-Meneses FA , Peralta H , Zuniga-Moya JC , Lainez Arteaga IZ , Garcia A , Abdo J , Verweij PE , Chiller TM , Forno D . Mycoses 2021 64 (11) 1396-1401 OBJECTIVES: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory assays, based on microscopy and culture, are not optimal for the diagnosis of either disease. However, antigen (Ag) assays are rapid and highly accurate for the diagnosis of these infections. METHODS: Laboratory surveillance of PLHIV was carried out in four hospitals in Panama, Honduras, and Nicaragua, between 2015 and 2019. Detection of Histoplasma antigens in urine was performed by enzyme immunoassay (EIA), and Cryptococcus antigen detection in sera and cerebrospinal fluid specimens was performed by lateral flow assay (LFA). RESULTS: A total of 4,453 PLHIV with clinical suspicion of histoplasmosis (n=1,343) or cryptococcosis (n=3,110; 2,721 sera and 389 CSF) were tested. Of 1,343 patients suspected of having histoplasmosis, 269 (20%) were Histoplasma Ag positive. Of 3,110 patients tested using the Cryptococcus Ag assay, 329 (11%) were positive. Honduras reported the highest positivity rates (32% for Histoplasma Ag, and 16% for Cryptococcus Ag); Panama reported the largest number of patients testing positive using the Histoplasma Ag assay (n=201); and Nicaragua reported the largest number of patients testing positive using the Cryptococcus Ag assay (n=170). CONCLUSION: Here we show how the implementation of rapid diagnostics assays impacted case detection and were useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV. |
Trends in Agricultural Triazole Fungicide Use in the United States, 1992-2016 and Possible Implications for Antifungal-Resistant Fungi in Human Disease
Toda M , Beer KD , Kuivila KM , Chiller TM , Jackson BR . Environ Health Perspect 2021 129 (5) 55001 BACKGROUND: The fungus Aspergillus fumigatus (A. fumigatus) is the leading cause of invasive mold infections, which cause severe disease and death in immunocompromised people. Use of triazole antifungal medications in recent decades has improved patient survival; however, triazole-resistant infections have become common in parts of Europe and are emerging in the United States. Triazoles are also a class of fungicides used in plant agriculture, and certain triazole-resistant A. fumigatus strains found causing disease in humans have been linked to environmental fungicide use. OBJECTIVES: We examined U.S. temporal and geographic trends in the use of triazole fungicides using U.S. Geological Survey agricultural pesticide use estimates. DISCUSSION: Based on our analysis, overall tonnage of triazole fungicide use nationwide was relatively constant during 1992-2005 but increased > 4-fold during 2006-2016 to 2.9 million kg in 2016. During 1992-2005, triazole fungicide use occurred mostly in orchards and grapes, wheat, and other crops, but recent increases in use have occurred primarily in wheat, corn, soybeans, and other crops, particularly in Midwest and Southeast states. We conclude that, given the chemical similarities between triazole fungicides and triazole antifungal drugs used in human medicine, increased monitoring for environmental and clinical triazole resistance in A. fumigatus would improve overall understanding of these interactions, as well as help identify strategies to mitigate development and spread of resistance. https://doi.org/10.1289/EHP7484. |
Coronavirus Disease 2019 (COVID-19) in a Patient with Disseminated Histoplasmosis and HIV-A Case Report from Argentina and Literature Review.
Messina FA , Marin E , Caceres DH , Romero M , Depardo R , Priarone MM , Rey L , Vázquez M , Verweij PE , Chiller TM , Santiso G . J Fungi (Basel) 2020 6 (4) The disease caused by the new SARS-CoV-2, known as Coronavirus disease 2019 (COVID-19), was first identified in China in December 2019 and rapidly spread around the world. Coinfections with fungal pathogens in patients with COVID-19 add challenges to patient care. We conducted a literature review on fungal coinfections in patients with COVID-19. We describe a report of a patient with disseminated histoplasmosis who was likely infected with SARS-CoV-2 and experienced COVID-19 during hospital care in Buenos Aires, Argentina. This patient presented with advanced HIV disease, a well-known factor for disseminated histoplasmosis; on the other hand, we suspected that COVID-19 was acquired during hospitalization but there is not enough evidence to support this hypothesis. Clinical correlation and the use of specific Histoplasma and COVID-19 rapid diagnostics assays were key to the timely diagnosis of both infections, permitting appropriate treatment and patient care. |
Case-case comparison of Candida auris versus other Candida species bloodstream infections: Results of an outbreak investigation in Colombia
Caceres DH , Rivera SM , Armstrong PA , Escandon P , Chow NA , Ovalle MV , Díaz J , Derado G , Salcedo S , Berrio I , Espinosa-Bode A , Varón C , Stuckey MJ , Mariño A , Villalobos N , Lockhart SR , Chiller TM , Prieto FE , Jackson BR . Mycopathologia 2020 185 (5) 917-923 BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that causes outbreaks in healthcare settings around the world. In 2016, clinicians and public health officials identified patients with C. auris bloodstream infections (BSI) in Colombian healthcare facilities. To evaluate potential risk factors and outcomes for these infections, we investigated epidemiologic and clinical features of patients with C. auris and other Candida species BSI. METHODS: We performed a retrospective case-case investigation in four Colombian acute care hospitals, defining a case as Candida spp. isolated from blood culture during January 2015-September 2016. C. auris BSI cases were compared to other Candida species BSI cases. Odds ratio (OR), estimated using logistic regression, was used to assess the association between risk factors and outcomes. RESULTS: We analyzed 90 patients with BSI, including 40 with C. auris and 50 with other Candida species. All had been admitted to the intensive care unit (ICU). No significant demographic differences existed between the two groups. The following variables were independently associated with C. auris BSI: ≥ 15 days of pre-infection ICU stay (OR: 5.62, CI: 2.04-15.5), evidence of severe sepsis (OR: 3.70, CI 1.19-11.48), and diabetes mellitus (OR 5.69, CI 1.01-31.9). CONCLUSION: Patients with C. auris BSI had longer lengths of ICU stay than those with other candidemias, suggesting that infections are acquired during hospitalization. This is different from other Candida infections, which are usually thought to result from autoinfection with host flora. |
Long-term outcomes of patients with fungal infections associated with contaminated methylprednisolone injections
Malani AN , Kauffman CA , Latham R , Peglow S , Ledtke CS , Kerkering TM , Kaufman DH , Triplett PF , Wright PW , Bloch KC , McCotter O , Toda M , Jackson BR , Pappas PG , Chiller TM . Open Forum Infect Dis 2020 7 (6) ofaa164 Background: The largest health care-associated infection outbreak in the United States occurred during 2012-2013. Following injection of contaminated methylprednisolone, 753 patients developed infection with a dematiaceous mold, Exserohilum rostratum. The long-term outcomes of these infections have not been described. Methods: This retrospective cohort study of 440 of a total of 753 patients with proven or probable Exserohilum infection evaluated clinical and radiographic findings, antifungal therapy and associated adverse effects, and outcomes at 6 weeks, 3, 6, 9, and 12 months after diagnosis. Patients were grouped into 4 disease categories: meningitis with/without stroke, spinal or paraspinal infections, meningitis/stroke plus spinal/paraspinal infections, and osteoarticular infections. Results: Among the 440 patients, 223 (51%) had spinal/paraspinal infection, 82 (19%) meningitis/stroke, 123 (28%) both, and 12 (3%) osteoarticular infection. Of 82 patients with meningitis/stroke, 18 (22%) died; among those surviving, 87% were cured at 12 months. Only 7 (3%) of 223 patients with spinal/paraspinal infection died, but at 12 months, 68% had persistent or worsening pain and only 47% were cured. For the 123 patients with both meningitis/stroke and spinal/paraspinal infection, 10 (8%) died, pain persisted in 72%, and 52% were cured at 12 months. Only 37% of those with osteoarticular infection were cured at 12 months. Adverse events from antifungal therapy were noted at 6 weeks in 71% of patients on voriconazole and 81% on amphotericin B. Conclusions: Fungal infections related to contaminated methylprednisolone injections culminated in death in 8% of patients. Persistent pain and disability were seen at 12 months in most patients with spinal/paraspinal infections. |
Knowledge of infectious disease specialists regarding aspergillosis complicating influenza, United States
Toda M , Beekmann SE , Polgreen PM , Chiller TM , Jackson BR , Beer KD . Emerg Infect Dis 2020 26 (4) 809-811 In an online survey, we found that nearly one fifth of physicians in the United States who responded had seen or heard about a case of invasive pulmonary aspergillosis after severe influenza at their institution. However, <10% routinely used galactomannan testing to test for this fungus in patients with severe influenza. |
Bridging the knowledge gap on mycoses in Africa; setting up a Pan-African Mycology Working Group
Oladele RO , Akase IE , Fahal A , Govender NP , Honigl M , Gangneux JP , Chiller TM , Denning DW , Cornely OA , Chakrabarti A . Mycoses 2019 63 (3) 244-249 Most African countries have poorly funded and overburdened health systems. Additionally, a high prevalence of HIV in Sub-Saharan Africa contributes to a high burden of opportunistic fungal infections. Data generated by GAFFI from 15 of 57 African countries revealed that an estimated 47 million Africans suffer from fungal diseases, of whom an estimated 1.7 million suffer from a serious fungal infection annually. Almost all African countries lack a surveillance system for fungal infections with the exception of South Africa. South Africa is also the only African country with a national mycology reference laboratory. Across the continent, there is a pervasive picture of inadequate/poor diagnostic capacity, low level of awareness among health care workers and policy makers as well as unavailability and non-accessibility to essential antifungal medications. Recent outreach efforts by the International Society for Human and Animal Mycology (ISHAM) and the European Confederation of Medical Mycology (ECMM) have aimed to increase involvement of African countries and experts in global initiatives such as "One World One Guideline" and also the ECMM Academy. Recently, under the auspices of ISHAM, the African sub-region created a network of mycology experts whose goal is organize and engage African leaders in the field of medical mycology. The aim of this ISHAM Working Group is to facilitate interaction and synergy among regional leaders in order to develop educational programs for capacity building to aid in the diagnosis and care of patients with fungal infections in Africa. The working group will also encourage country initiatives to develop clinical guidelines, to support surveys, and to support the establishment of reference mycology laboratories. |
The changing epidemiology of candidemia in the United States: Injection drug use as an increasingly common risk factor - active surveillance in selected sites, United States, 2014-17
Zhang AY , Shrum S , Williams S , Petnic S , Nadle J , Johnston H , Barter D , VonBank B , Bonner L , Hollick R , Marceaux K , Harrison L , Schaffner W , Tesini BL , Farley MM , Pierce RA , Phipps E , Mody RK , Chiller TM , Jackson BR , Vallabhaneni S . Clin Infect Dis 2019 71 (7) 1732-1737 BACKGROUND: Injection drug use (IDU) is a known, but infrequent risk factor on candidemia, however, the opioid epidemic and increases in IDU may be changing the epidemiology of candidemia. METHODS: Active population-based surveillance for candidemia was conducted in selected US counties. Cases of candidemia were categorized as IDU cases if IDU was indicated in the medical records in the 12 months prior to the date of initial culture. RESULTS: During 2017, 1191 candidemia cases were identified in patients over the age of 12 years (incidence: 6.9 per 100,000 population); 128 (10.7%) had IDU history and this proportion was especially high (34.6%) in patients with candidemia aged 19-44 years. Candidemia patients with IDU history were younger than those without (median age: 35 vs 63 years, p<0.001). Candidemia cases involving recent IDU were less likely to have typical risk factors including malignancy (7.0% vs 29.4%, Relative Risk (RR): 0.2; 95% Confidence Interval (CI): 0.1-0.5), abdominal surgery (3.9% vs 17.5%, RR: 0.2, CI: 0.09-0.5), and total parenteral nutrition (3.9% vs 22.5%, RR: 0.2, CI: 0.07-0.4). Candidemia cases with IDU occurred more commonly in smokers (68.8% vs 18.5%, RR: 3.7, CI: 3.1-4.4), those with hepatitis C (54.7% vs 6.4%, RR: 8.5, CI: 6.5-11.3), and in people who were homeless (13.3% vs 0.8%, RR: 15.7; CI: 7.1-34.5). CONCLUSION: Clinicians should consider screening for candidemia in people who inject drugs and IDU in patients with candidemia who lack typical candidemia risk factors, especially in those with who are 19-44 years, and have community-associated candidemia. |
Evaluation of a Histoplasma antigen Lateral Flow Assay for the rapid diagnosis of progressive disseminated histoplasmosis in Colombian patients with AIDS
Caceres DH , Gomez BL , Tobon AM , Chiller TM , Lindsley MD . Mycoses 2019 63 (2) 139-144 BACKGROUND: Progressive disseminated histoplasmosis (PDH) is an important cause of mortality in persons living with HIV (PLHIV), especially in countries where patients have limited access to antiretroviral therapies and diagnostic testing. OBJECTIVE: A Lateral Flow Assay (LFA) to detect Histoplasma capsulatum antigen in serum developed by MiraVista((R)) was evaluated. METHODS: We tested 75 serum samples: 24 from PLHIV and culture-proven PDH and 51 from PLHIV with other fungal and bacterial infections as well as people without HIV. LFA devices were read manually (read by eye) and by an automated reader. RESULTS: When the LFA was read manually, sensitivity was 96% and specificity was 90%. When an automated reader was used, sensitivity was 92% and specificity was 94%. The Kappa index comparing manual and automated reader was 0.90. Cross-reactions were observed principally in samples from patients with proven diagnosis of paracoccidioidomycosis. CONCLUSIONS: The MiraVista((R)) Diagnostics Histoplasma antigen LFA had high analytical performance and good agreement between manual and automated reader. This LFA allows Histoplasma antigen testing with minimal laboratory equipment and infrastructure requirements. |
Potential Fifth Clade of Candida auris, Iran, 2018.
Chow NA , de Groot T , Badali H , Abastabar M , Chiller TM , Meis JF . Emerg Infect Dis 2019 25 (9) 1780-1781 Four major clades of Candida auris have been described, and all infections have clustered in these 4 clades. We identified an isolate representative of a potential fifth clade, separated from the other clades by >200,000 single-nucleotide polymorphisms, in a patient in Iran who had never traveled outside the country. |
Hospital-associated multicenter outbreak of emerging fungus Candida auris, Colombia, 2016
Armstrong PA , Rivera SM , Escandon P , Caceres DH , Chow N , Stuckey MJ , Diaz J , Gomez A , Velez N , Espinosa-Bode A , Salcedo S , Marin A , Berrio I , Varon C , Guzman A , Perez-Franco JE , Escobar JD , Villalobos N , Correa JM , Litvintseva AP , Lockhart SR , Fagan R , Chiller TM , Jackson B , Pacheco O . Emerg Infect Dis 2019 25 (7) 1339-46 Candida auris is an emerging multidrug-resistant fungus that causes hospital-associated outbreaks of invasive infections with high death rates. During 2015-2016, health authorities in Colombia detected an outbreak of C. auris. We conducted an investigation to characterize the epidemiology, transmission mechanisms, and reservoirs of this organism. We investigated 4 hospitals with confirmed cases of C. auris candidemia in 3 cities in Colombia. We abstracted medical records and collected swabs from contemporaneously hospitalized patients to assess for skin colonization. We identified 40 cases; median patient age was 23 years (IQR 4 months-56 years). Twelve (30%) patients were <1 year of age, and 24 (60%) were male. The 30-day mortality was 43%. Cases clustered in time and location; axilla and groin were the most commonly colonized sites. Temporal and spatial clustering of cases and skin colonization suggest person-to-person transmission of C. auris. These cases highlight the importance of adherence to infection control recommendations. |
Candida auris: An emerging antimicrobial resistance threat
Vallabhaneni S , Jackson BR , Chiller TM . Ann Intern Med 2019 171 (6) 432-433 Candida auris is becoming a household name—no easy feat for a fungus. This multidrug-resistant yeast, first reported in 2009 after it was found in the ear canal of a patient in Japan, has since caused invasive infections in more than 30 countries spanning every inhabited continent (1). It is an urgent threat because many strains are resistant to at least 2 of the 3 major classes of antifungal drugs used to treat Candida infections and because it causes outbreaks in health care settings to an extent not seen with other Candida species. |
Essential in vitro diagnostics for advanced HIV and serious fungal diseases: international experts' consensus recommendations
Bongomin F , Govender NP , Chakrabarti A , Robert-Gangneux F , Boulware DR , Zafar A , Oladele RO , Richardson MD , Gangneux JP , Alastruey-Izquierdo A , Bazira J , Boyles TH , Sarcarlal J , Nacher M , Obayashi T , Worodria W , Pasqualotto AC , Meya DB , Cheng B , Sriruttan C , Muzoora C , Kambugu A , Rodriguez Tudela JL , Jordan A , Chiller TM , Denning DW . Eur J Clin Microbiol Infect Dis 2019 38 (9) 1581-1584 An accurate, timely diagnosis is the cornerstone of good medical practice. For opportunistic fungal infections in AIDS and other invasive mycoses, this is dependent on the availability of and accessibility to the relevant diagnostic tests. A call for a model List of Essential In Vitro Diagnostics (EDL)—“listed tests that should be reasonably available for people who need them, whether in the form of point-of-care tests in physicians’ offices and pharmacies or as high-complexity tests in reference laboratories”—has been published [1]. In addition to better medical practice, other potential benefits of an EDL include clarification of priorities for policy makers, setting common goals for laboratory testing, improved healthcare delivery and overall better patient outcomes [1]. In the context of extensive antimicrobial resistance (AMR), a reduction in empiricism with more accurate diagnosis will play a key role in AMR control [2]. |
Hurricane-associated mold exposures among patients at risk for invasive mold infections after Hurricane Harvey - Houston, Texas, 2017
Chow NA , Toda M , Pennington AF , Anassi E , Atmar RL , Cox-Ganser JM , Da Silva J , Garcia B , Kontoyiannis DP , Ostrosky-Zeichner L , Leining LM , McCarty J , Al Mohajer M , Murthy BP , Park JH , Schulte J , Shuford JA , Skrobarcek KA , Solomon S , Strysko J , Chiller TM , Jackson BR , Chew GL , Beer KD . MMWR Morb Mortal Wkly Rep 2019 68 (21) 469-473 In August 2017, Hurricane Harvey caused unprecedented flooding and devastation to the Houston metropolitan area (1). Mold exposure was a serious concern because investigations after Hurricanes Katrina and Rita (2005) had documented extensive mold growth in flood-damaged homes (2,3). Because mold exposure can cause serious illnesses known as invasive mold infections (4,5), and immunosuppressed persons are at high risk for these infections (6,7), several federal agencies recommend that immunosuppressed persons avoid mold-contaminated sites (8,9). To assess the extent of exposure to mold and flood-damaged areas among persons at high risk for invasive mold infections after Hurricane Harvey, CDC and Texas health officials conducted a survey among 103 immunosuppressed residents in Houston. Approximately half of the participants (50) engaged in cleanup of mold and water-damaged areas; these activities included heavy cleanup (23), such as removing furniture or removing drywall, or light cleanup (27), such as wiping down walls or retrieving personal items. Among immunosuppressed persons who performed heavy cleanup, 43% reported wearing a respirator, as did 8% who performed light cleanup. One participant reported wearing all personal protective equipment (PPE) recommended for otherwise healthy persons (i.e., respirator, boots, goggles, and gloves). Immunosuppressed residents who are at high risk for invasive mold infections were exposed to mold and flood-damaged areas after Hurricane Harvey; recommendations from health care providers to avoid exposure to mold and flood-damaged areas could mitigate the risk to immunosuppressed persons. |
Notes from the Field: Multistate coccidioidomycosis outbreak in U.S. residents returning from community service trips to Baja California, Mexico - July-August 2018
Toda M , Gonzalez FJ , Fonseca-Ford M , Franklin P , Huntington-Frazier M , Gutelius B , Kawakami V , Lunquest K , McCracken S , Moser K , Oltean H , Ratner AJ , Raybern C , Signs K , Zaldivar A , Chiller TM , Jackson BR , McCotter O . MMWR Morb Mortal Wkly Rep 2019 68 (14) 332-333 On August 8, 2018, the New York City Department of Health and Mental Hygiene notified CDC about two high school students hospitalized for pneumonia of unknown etiology who had recently returned from community service trips constructing houses near Tijuana in Baja California, Mexico. Patients had developed fever 9 and 11 days after travel, followed by rash and lower respiratory symptoms. Symptoms did not improve with multiple courses of antibacterial medications, and the patients subsequently received diagnoses of coccidioidomycosis, a fungal disease commonly known as valley fever. |
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