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.
Sporothrix , Sporotrichosis , Animals , Humans , Sporotrichosis/epidemiology , Sporotrichosis/veterinary , Sporotrichosis/microbiology , Brazil/epidemiology , Phylogeny , Disease Outbreaks , Genomics , Sporothrix/genetics
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 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.
Candida auris ha sido reconocido como un agente patógeno multirresistente emergente con una carga significativa en la salud pública. Genera casos de infección invasiva y colonización debido a su persistencia en superficies inanimadas, su capacidad para colonizar fácilmente la piel de algunos pacientes y su alta transmisibilidad en el ambiente hospitalario. El primer reporte esporádico de esta especie fue en Asia en el 2009 cuando se realizó su aislamiento a partir del conducto auditivo de un paciente, y pronto le siguieron reportes en otras regiones del mundo. Sin embargo, no fue hasta 2015 que se conocieron las alertas epidemiológicas a nivel mundial debido a un aumento en el número de casos de infecciones causadas por C. auris en varios países. Colombia se sumó a la lista en 2016 luego de un aumento inusual en el número de aislamientos de C. haemulonii informados, que luego se confirmaron como C. auris. Desde que el Instituto Nacional de Salud junto con el Ministerio de Salud emitieron la Alerta Nacional en el 2016, el número de casos reportados superó los 2.000 en el 2022. Los aislamientos colombianos no han mostrado resistencia generalizada a los antifúngicos disponibles, contrario a lo reportado para cepas de C. auris en algunas regiones del mundo, por lo que los pacientes en Colombia aún cuentan con opciones terapéuticas para estas infecciones. No obstante, se ha observado un aumento en la resistencia al fluconazol.
Candida auris , Skin , Colombia , Asia
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. Data from Colombia showed that public health authorities, scientific community, and the general public need to be aware of fungal diseases as they present an often-deadly threat to patients.
Candida auris ha sido reconocido como un agente patógeno multirresistente emergente con una carga significativa en la salud pública. Genera casos de infección invasiva y colonización debido a su persistencia en superficies inanimadas, su capacidad para colonizar fácilmente la piel de algunos pacientes y su alta transmisibilidad en el ambiente hospitalario. El primer reporte esporádico de esta especie fue en Asia en el 2009 cuando se realizó su aislamiento a partir del conducto auditivo de un paciente, y pronto le siguieron reportes en otras regiones del mundo. Sin embargo, no fue hasta 2015 que se conocieron las alertas epidemiológicas a nivel mundial debido a un aumento en el número de casos de infecciones causadas por C. auris en varios países. Colombia se sumó a la lista en 2016 luego de un aumento inusual en el número de aislamientos de C. haemulonii informados, que luego se confirmaron como C. auris. Desde que el Instituto Nacional de Salud junto con el Ministerio de Salud emitieron la Alerta Nacional en el 2016, el número de casos reportados superó los 2.000 en el 2022. Los aislamientos colombianos no han mostrado resistencia generalizada a los antifúngicos disponibles, contrario a lo reportado para cepas de C. auris en algunas regiones del mundo, por lo que los pacientes en Colombia aún cuentan con opciones terapéuticas para estas infecciones. No obstante, se ha observado un aumento en la resistencia al fluconazol. La secuenciación del genoma completo agrupó los aislamientos colombianos en el Ciado IV, junto con otros sudamericanos de C. auris, y aportó al conocimiento de los datos epidemiológicos moleculares de esta especie. Los datos de Colombia evidencian que las autoridades de salud pública, la comunidad científica y el público en general deben ser conscientes de las enfermedades fúngicas, ya que a menudo representan una amenaza mortal para los pacientes.
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.
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.
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 to 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 to 10 SNPs and two patients ranged from 2 to 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.
Aspergillosis , Aspergillus fumigatus , Humans , Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Aspergillosis/veterinary , Aspergillus fumigatus/genetics , California , Genomics , Phylogeny
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.
HIV Infections , Meningitis, Cryptococcal , Humans , Amphotericin B/therapeutic use , Amphotericin B/adverse effects , Meningitis, Cryptococcal/drug therapy , Flucytosine/therapeutic use , Flucytosine/adverse effects , Fluconazole/therapeutic use , Antifungal Agents/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Drug Therapy, Combination , Randomized Controlled Trials as Topic
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.
AIDS-Related Opportunistic Infections , Acquired Immunodeficiency Syndrome , Cryptococcosis , Cryptococcus , HIV Infections , Meningitis, Cryptococcal , Adult , Humans , AIDS-Related Opportunistic Infections/diagnosis , Acquired Immunodeficiency Syndrome/complications , CD4 Lymphocyte Count , HIV Infections/complications , HIV Infections/epidemiology , Antigens, Fungal , Cryptococcosis/epidemiology , Cryptococcosis/diagnosis
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 aetiological 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.
Cyclonic Storms , Neoplasms , Antifungal Agents/therapeutic use , Floods , Fungi , Humans , Immunocompromised Host , Neoplasms/complications , Neoplasms/epidemiology
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.
Histoplasma , Histoplasmosis , Antigens, Fungal , Histoplasmosis/diagnosis , Humans , Immunoenzyme Techniques , Sensitivity and Specificity
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.
Disease Outbreaks , Public Health , Fungi , Hospitals , Humans , Personnel, Hospital
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 was useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV.
Cryptococcosis/diagnosis , HIV Infections/complications , Histoplasmosis/diagnosis , Adult , Antigens, Fungal/blood , Antigens, Fungal/cerebrospinal fluid , Antigens, Fungal/urine , Cryptococcus/immunology , Female , Flow Cytometry , Histoplasma/immunology , Honduras , Humans , Immunoenzyme Techniques , Male , Nicaragua , Panama
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.
Agriculture , Fungicides, Industrial , Triazoles , Agriculture/trends , Drug Resistance, Fungal , Fungi/drug effects , Fungicides, Industrial/pharmacology , Humans , Triazoles/pharmacology , United States
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.
Fungi , Mycoses/epidemiology , Aspergillus , Blastomyces , Candida , Coccidioides , Cryptococcus , Disease Susceptibility , Histoplasma , Humans , North America/epidemiology
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.
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.
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.
