Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 45 Records) |
Query Trace: Cáceres DH [original query] |
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Cost-effectiveness evaluation of routine histoplasmosis screening among people living with advanced HIV disease in Latin America and the Caribbean
Rajasingham R , Medina N , Mousquer GT , Caceres DH , Jordan A , Nacher M , Falci DR , Sebro A , Pasqualotto AC , Sued O , Chiller T , Perez F . PLOS Glob Public Health 2023 3 (8) e0001861 Histoplasma antigen can be detected in people with advanced HIV disease (AHD), allowing for early and accurate diagnosis of histoplasmosis. The aim of this analysis was to assess the cost-effectiveness of routine histoplasmosis screening using antigen detection, among people with AHD. We developed a decision analytic model to evaluate Histoplasma antigen screening among people with AHD. The model estimated the costs, effectiveness, and cost-effectiveness of routine screening for Histoplasma antigen compared to the current practice of no routine Histoplasma antigen screening. The model includes stratification by symptoms of histoplasmosis, severity of presentation, and estimates of 30-day mortality. Data sources were taken from the Pan American Health Organization (PAHO) Strategic Fund databases on public purchases of medicines, and published literature on treatment outcomes. Outcome measures are life years saved (LYS), costs (US dollars), and incremental cost-effectiveness ratios (ICERs). Routine Histoplasma antigen screening avoids an estimated 17% of deaths in persons with advanced HIV disease, and is cost-effective compared to no histoplasmosis screening, with an ICER of $26/LYS. In sensitivity analysis assuming treatment for histoplasmosis with liposomal amphotericin, Histoplasma antigen screening remains cost-effective with an ICER of $607/LYS. Histoplasma antigen screening among people with AHD is a cost-effective strategy and could potentially avert 17% of AIDS-related deaths. Prospective evaluation of histoplasmosis screening is warranted to determine effectiveness and treatment outcomes with this strategy. |
Application of real-time PCR assays for the diagnosis of histoplasmosis in human FFPE tissues using three molecular targets
López LF , Tobón Á M , Cáceres DH , Chiller T , Litvintseva AP , Gade L , González Á , Gómez BL . J Fungi (Basel) 2023 9 (7) Histoplasmosis is a fungal infection caused by the thermally dimorphic fungus Histoplasma capsulatum. This infection causes significant morbidity and mortality in people living with HIV/AIDS, especially in countries with limited resources. Currently used diagnostic tests rely on culture and serology but with some limitations. No molecular assays are commercially available and the results from different reports have been variable. We aimed to evaluate quantitative real-time PCR (qPCR) targeting three protein-coding genes of Histoplasma capsulatum (100-kDa, H and M antigens) for detection of this fungus in formalin-fixed paraffin-embedded (FFPE) samples from patients with proven histoplasmosis. The sensitivity of 100-kDa, H and M qPCR assays were 93.9%, 91% and 57%, respectively. The specificity of 100-kDa qPCR was 93% when compared against samples from patients with other mycoses and other infections, and 100% when samples from patients with non-infectious diseases were used as controls. Our findings demonstrate that real-time PCR assays targeting 100-kDa and H antigen showed the most reliable results and can be successfully used for diagnosing this mycosis when testing FFPE samples. |
Tackling histoplasmosis infection in people living with HIV from Latin America: From diagnostic strategy to public health solutions
Cáceres DH , Gómez BL , Tobón Á M , Restrepo Á , Chiller T , Lindsley MD , Meis JF , Verweij PE . J Fungi (Basel) 2023 9 (5) Histoplasmosis, caused by the thermally dimorphic fungus Histoplasma spp., is a disease with a broad clinical spectrum, presenting from asymptomatic/flu-like symptoms to progressive disseminated disease in people with immunosuppression. In recent years, the concept of histoplasmosis as a disease restricted to the American continent has changed, as now histoplasmosis is reported in many regions around the world. In Latin America, histoplasmosis represents a threat, especially in people with advanced HIV disease (AHD). Diagnosis of histoplasmosis in people living with HIV (PLHIV) is challenging due to the low index of suspicion of the disease, non-specificity of signs and symptoms, and limited access to specific laboratory testing, while the diagnostic delay is significantly associated with mortality. In the last decade, novel diagnostic tests have been developed for the rapid detection of histoplasmosis, such as commercial kits for antigen detection. Furthermore, advocacy groups were created that presented histoplasmosis as a public health problem, with emphasis on patients at risk of progressive disseminated disease. This review aims to discuss the impact of histoplasmosis associated with AHD in Latin America and the strategies employed to tackle histoplasmosis, from the implementation of laboratory testing to disease advocacy and public health interventions. |
Validation and concordance analysis of a new lateral flow assay for detection of histoplasma antigen in urine
Cáceres DH , Gómez BL , Tobón Á M , Minderman M , Bridges N , Chiller T , Lindsley MD . J Fungi (Basel) 2021 7 (10) Histoplasmosis is a major cause of mortality in people living with HIV (PLHIV). Rapid methods to diagnose Histoplasma capsulatum disease could dramatically decrease the time to initiate treatment, resulting in reduced mortality. The aim of this study was to validate a MiraVista(®) Diagnostics (MVD) Histoplasma urine antigen lateral flow assay (MVD LFA) for the detection of H. capsulatum antigen (Ag) in urine and compare this LFA against the MVista(®) Histoplasma Ag quantitative enzyme immunoassays (MVD EIA). We assessed the MVD LFA using a standardized reference panel of urine specimens from Colombia. We tested 100 urine specimens, 26 from PLHIV diagnosed with histoplasmosis, 42 from PLHIV with other infectious diseases, and 32 from non-HIV infected persons without histoplasmosis. Sensitivity and specificity of the MVD LFA was 96%, compared with 96% sensitivity and 77% specificity of the MVD EIA. Concordance analysis between MVD LFA and the MVD EIA displayed an 84% agreement, and a Kappa of 0.656. The MVD LFA evaluated in this study has several advantages, including a turnaround time for results of approximately 40 min, no need for complex laboratory infrastructure or highly trained laboratory personnel, use of urine specimens, and ease of performing. |
Fungal pathogens as causes of acute respiratory illness in hospitalized veterans: Frequency of fungal positive test results using rapid immunodiagnostic assays
Caceres DH , Rodriguez-Barradas MC , Whitaker M , Jackson BR , Kim L , Surie D , Cikesh B , Lindsley MD , McCotter OZ , Berkow EL , Toda M . J Fungi (Basel) 2023 9 (4) Fungal respiratory illnesses caused by endemic mycoses can be nonspecific and are often mistaken for viral or bacterial infections. We performed fungal testing on serum specimens from patients hospitalized with acute respiratory illness (ARI) to assess the possible role of endemic fungi as etiologic agents. Patients hospitalized with ARI at a Veterans Affairs hospital in Houston, Texas, during November 2016-August 2017 were enrolled. Epidemiologic and clinical data, nasopharyngeal and oropharyngeal samples for viral testing (PCR), and serum specimens were collected at admission. We retrospectively tested remnant sera from a subset of patients with negative initial viral testing using immunoassays for the detection of Coccidioides and Histoplasma antibodies (Ab) and Cryptococcus, Aspergillus, and Histoplasma antigens (Ag). Of 224 patient serum specimens tested, 49 (22%) had positive results for fungal pathogens, including 30 (13%) by Coccidioides immunodiagnostic assays, 19 (8%) by Histoplasma immunodiagnostic assays, 2 (1%) by Aspergillus Ag, and none by Cryptococcus Ag testing. A high proportion of veterans hospitalized with ARI had positive serological results for fungal pathogens, primarily endemic mycoses, which cause fungal pneumonia. The high proportion of Coccidioides positivity is unexpected as this fungus is not thought to be common in southeastern Texas or metropolitan Houston, though is known to be endemic in southwestern Texas. Although serological testing suffers from low specificity, these results suggest that these fungi may be more common causes of ARI in southeast Texas than commonly appreciated and more increased clinical evaluation may be warranted. |
The use of readily available laboratory tests for the identification of the emerging yeast Candida auris in Mexico
González-Durán E , Contreras-Pérez CU , Caceres DH , Ríos-Rosas C , Piñón-Ortega JJ , Téllez-Saucedo MD , Marín-Suro ES , Wong-Arámbula CE , Moreno-Escobar EA , Ramírez-González JE , Ramírez-Barrios JG , Montes-Colima NA , Lockhart SR , Martínez-Montiel N , Martínez-Contreras RD , García-Ruíz P , Salazar-Sánchez MI , Hernández-Rivas L , López-Martínez I . Arch Microbiol 2022 204 (9) 592 Identification of the emerging multidrug-resistant yeast Candida auris is challenging. Here, we describe the role of the Mexico national reference laboratory Instituto de Diagnóstico y Referencia Epidemiológicos Dr. Manuel Martínez Báez (InDRE) and the Mexican national laboratory network in the identification of C. auris. Reference identification of six suspected isolates was done based on phenotypic and molecular laboratory methods, including growth in special media, evaluation of isolate micromorphology, and species-specific PCR and pan-fungal PCR and sequencing. The four C. auris isolates identified were able to grow on modified Sabouraud agar with 10% NaCl incubated at 42 °C. With one exception, isolates of C. auris were spherical to ovoid yeast-like cells and blastoconidia, with no hyphae or pseudohyphae on cornmeal agar. C. auris isolates were resistant to fluconazole. Species-specific and pan-fungal PCR confirmed isolates as C. auris. Sequence analysis revealed the presence of two different C. auris clades in Mexico, clade I (South Asia) and clade IV (South America). |
Comparison of immunodiagnostic assays for the rapid diagnosis of coccidioidomycosis in dogs
Caceres DH , Lindsley MD . J Fungi (Basel) 2022 8 (7) Coccidioidomycosis is a disease caused by the dimorphic fungi Coccidioides spp., which affects humans and a variety of animal species, including domestic dogs. In dogs, accurate diagnosis could provide a substantial improvement on the quality of canine life, as well as an advancement in the mapping of regions endemic for coccidioidomycosis. The purpose of this study was to compare immunodiagnostic assays for anti-Coccidioides antibody (Ab) detection in dogs' serum. Three commercially available immunodiagnostic assays (IMMY(); Norman, OK, USA) were evaluated, including the sna Coccidioides Ab Lateral Flow Assay (LFA), Coccidioides IDCF immunodiffusion assay (IDCF), and the Clarus Coccidioides Ab Enzyme Immunoassay (EIA). Assays were evaluated using 98 dog serum samples: 29 from dogs with coccidioidomycosis, 15 from dogs diagnosed with histoplasmosis, 10 from dogs diagnosed with blastomycosis, and 44 from dogs without a fungal disease. Using specimens from dogs with coccidioidomycosis, the IDCF had an accuracy of 92% (95% confidence interval [95% CI] = 85-96%), the EIA had an accuracy of 91% (95% CI = 83-96%), and the LFA displayed an accuracy of 82% (95% CI = 73-89%). Using Kappa analysis, the agreement between LFA and EIA was 0.59 (95% CI = 0.42-0.75), that between LFA and IDCF was 0.64 (95% CI = 0.48-0.79), and that between EIA and IDCF was 0.79 (95% CI = 0.64-0.90). Most cross-reactions were observed in dogs with histoplasmosis. Compared with EIA and IDCF, the LFA requires substantially less laboratory equipment and infrastructure and rapidly produces results, offering a substantial improvement for the initial screening of coccidioidomycosis in dogs. |
Current situation of endemic mycosis in the Americas and the Caribbean: Proceedings of the first International Meeting On Endemic Mycoses Of The Americas (IMEMA)
Caceres DH , EcheverriTirado LC , Bonifaz A , Adenis A , Gomez BL , Flores CLB , Canteros CE , Santos DW , Arathoon E , Soto ER , Queiroz-Telles F , Schwartz IS , Zurita J , Damasceno LS , Garcia N , Fernandez NB , Chincha O , Araujo P , Rabagliati R , Chiller T , Giusiano G . Mycoses 2022 65 (12) 1179-1187 BACKGROUND: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. OBJECTIVES: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). METHODS: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. RESULTS: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)--d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. CONCLUSIONS: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed. |
Notes from the Field: Mucormycosis Cases During the COVID-19 Pandemic - Honduras, May-September 2021.
Mejía-Santos H , Montoya S , Chacón-Fuentes R , Zielinski-Gutierrez E , Lopez B , Ning MF , Farach N , García-Coto F , Rodríguez-Araujo DS , Rosales-Pavón K , Urbina G , Rivera AC , Peña R , Tovar A , Paz MC , Lopez R , Pardo-Cruz F , Mendez C , Flores A , Varela M , Chiller T , Jackson BR , Jordan A , Lyman M , Toda M , Caceres DH , Gold JAW . MMWR Morb Mortal Wkly Rep 2021 70 (50) 1747-1749 On July 15, 2021, the Secretary of Health of Honduras (SHH) was notified of an unexpected number of mucormycosis cases among COVID-19 patients. SHH partnered with the Honduras Field Epidemiology Training Program, the Executive Secretariat of the Council of Ministers of Health of Central America and the Dominican Republic (SE-COMISCA), Pan American Health Organization (PAHO), and CDC to investigate mucormycosis cases at four geographically distinct hospitals in Honduras. | | Mucormycosis is a severe, often fatal disease caused by infection with angioinvasive molds belonging to the order Mucorales. Risk factors for mucormycosis include certain underlying medical conditions (e.g., hematologic malignancy, stem cell or solid organ transplantation, or uncontrolled diabetes) and the use of certain immunosuppressive medications (1). COVID-19 might increase mucormycosis risk because of COVID-19–induced immune dysregulation or associated medical treatments, such as systemic corticosteroids and other immunomodulatory drugs (e.g., tocilizumab), which impair the immune response against mold infections (2). In India, an apparent increase in mucormycosis cases (which was referred to by the misnomer “black fungus”) was attributed to COVID-19 (3). |
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. |
Laboratory-based surveillance of Candida auris in Colombia, 2016-2020.
Escandón P , Cáceres DH , Lizarazo D , Lockhart SR , Lyman M , Duarte C . Mycoses 2021 65 (2) 222-225 BACKGROUND: Since the first report of Candida auris in 2016, the Colombian Instituto Nacional de Salud (INS) has implemented a national surveillance of the emerging multidrug-resistant fungus. OBJECTIVES: This report summarizes the findings of this laboratory-based surveillance from March 2016 to December 2020. RESULTS: A total of 1,720 C. auris cases were identified, including 393 (23%) colonization cases and 1,327 (77%) clinical cases. Cases were reported in 20 of 32 (62%) Departments of Colombia and involved hospitals from 33 cities. The median age of patients was 34 years; 317 (18%) cases were in children under 16 years, 54% were male. The peak number of cases was observed in 2019 (n=541). In 2020, 379 (94%) of 404 cases reported were clinical cases, including 225 bloodstream infections (BSI) and 154 non-BSI. Among the 404 cases reported in 2020, severe COVID-19 was reported in 122 (30%). Antifungal susceptibility was tested in 379 isolates. Using CDC tentative breakpoints for resistance, 35% of isolates were fluconazole resistant, 33% were amphotericin B resistant, and 0.3% isolate were anidulafungin resistant, 12% were multidrug resistant, and no pan-resistant isolates were identified. CONCLUSION: For five years of surveillance, we observed an increase in the number and geographic spread of clinical cases and an increase in fluconazole resistance. These observations emphasize the need for improved measures to mitigate spread. |
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. |
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. |
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. |
Antifungal Activity of Boric Acid, Triclosan and Zinc Oxide Against Different Clinically Relevant Candida Species
Gavilanes-Martínez MA , Garzón AC , Cáceres DH , García AM . Mycoses 2021 64 (9) 1045-1052 BACKGROUND: The genus Candida includes about 200 different species, but only a few are able to produce disease in humans. The species responsible for the highest proportion of human infections is Candida albicans. However, in the last two decades there has been an increase in the proportion of infections caused by other Candida species, including C. glabrata (Nakaseomyces glabrata), C. parapsilosis, C. tropicalis, C. krusei (Pichia kudriavzevi) and more recently C. auris. Decolonization of patients has been used as an infection control strategy for bacterial infections, but information about decolonization products used in clinical practice for Candida and other fungal pathogens is limited. Compounds with antimicrobial activity, such as triclosan (TR), boric acid (BA) and zinc oxide (ZO), are mainly used in personal care products. These products can be used for long periods of time without an abrasive skin effect and are a possible alternative for patient decolonization in health care settings. OBJECTIVE: The aim of this study was to evaluate the antifungal activity of boric acid (BA), triclosan (TR) and zinc oxide (ZO), individually and combined, against clinically relevant Candida species. MATERIALS AND METHODS: Compounds to be screened for antifungal activity were evaluated at different concentrations, alone, and combined, using a well diffusion assay. The statistical evaluation was performed using analysis of variance (ANOVA) and a post hoc analysis using the multiple comparisons method. RESULTS: Individually, BA and TR showed antifungal activity against all Candida species evaluated but ZO did not show any antifungal activity. Mixtures of BA [5%] - TR [0.2%]; BA [5%] - TR [0.3%]; BA [5%] - TR [0.2%] - ZO [8.6%]; and BA [5%] - TR [0.2%] - ZO [25%] yielded the highest antifungal activity. An increased antifungal effect was observed in some mixtures when compared with individual compounds. CONCLUSIONS: We demonstrated antifungal activity of BA and TR against multiple Candida species, including against a clade of the emerging healthcare-associated pathogen C. auris. Additionally, this study shows enhancement of the antifungal effect and no antagonism among the mixtures of these compounds. Further research is needed to determine whether these compounds can reduce the burden of Candida on skin. |
Endemic and other dimorphic mycoses in the Americas
Lockhart SR , Toda M , Benedict K , Caceres DH , Litvintseva AP . J Fungi (Basel) 2021 7 (2) Endemic fungi are thermally dimorphic fungi that have a limited geographic range and can cause both primary disease and opportunistic infections. The Americas are home to more genera of endemic fungi than anywhere else on earth. These include Coccidioides, Histoplasma, Blastomyces, Paracoccidioides, and Sporothrix. Endemic fungi are found across the Americas and the Caribbean, from Blastomyces gilchristi, which extends into the northeast corners of North America, to Histoplasma capsulatum, which occurs all the way down in the southern regions of South America and into the Caribbean Islands. Symptoms of endemic fungal infection, when present, mimic those of many other diseases and are often diagnosed only after initial treatment for a bacterial or viral disease has failed. Endemic fungi place a significant medical burden on the populations they affect, especially in immunocompromised individuals and in resource-limited settings. This review summarizes the ecology, geographical range, epidemiology, and disease forms of the endemic fungi found in the Americas. An emphasis is placed on new and proposed taxonomic changes, including the assignment of new species names in Histoplasma, Blastomyces, and Paracoccidioides. |
Summary of guidelines for managing histoplasmosis among people living with HIV
Perez F , Caceres DH , Ford N , Ravasi G , Gomez BL , Pasqualotto AC , Hine P , Adenis AA , Nacher M , Chiller T , Baddley J . J Fungi (Basel) 2021 7 (2) Histoplasmosis is a frequent fungal opportunistic infection in people living with HIV (PLHIV), associated every year to a total of 5% to 15% of AIDS-related deaths among this population. In 2020, the first global guidelines for diagnosing and managing disseminated histoplasmosis among PLHIV was published. This document recommends (1) detection of circulating Histoplasma antigens as the recommended laboratory assay to diagnose histoplasmosis among PLHIV; (2) the use of liposomal amphotericin for induction therapy in severe or moderately severe disease, followed by a maintenance therapy with itraconazole for 12 months; a shorter maintenance therapy could be considered if the patient is clinically stable and if immune status has improved; (3) antiretroviral therapy initiation as soon as possible among patients with histoplasmosis without involvement of central nervous system; and (4) that for the treatment of co-infection with histoplasmosis and tuberculosis (TB), treatment of TB should be initiated according to the World Health Organization treatment guidelines. Appropriate health education of providers, supportive supervision, and policy guidance for the care of PLHIV are required. |
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. |
A One Health approach to combatting Sporothrix brasiliensis: Narrative review of an emerging zoonotic fungal pathogen in South America
Rossow JA , Queiroz-Telles F , Caceres DH , Beer KD , Jackson BR , Pereira JG , Ferreira Gremião ID , Pereira SA . J Fungi (Basel) 2020 6 (4) Cat-transmitted sporotrichosis caused by Sporothrix brasiliensis has become a major public health concern and presents a distinct divergence from the traditional epidemiology of sporotrichosis. This emerging fungal pathogen spreads readily among cat populations, and human infections occur exclusively via zoonotic transmission. While sporotrichosis is an implantation mycosis that typically manifests as cutaneous lesions in humans and cats, severe extracutaneous manifestations are more common with S. brasiliensis than other Sporothrix species infections. Rapid diagnosis and appropriate treatment regimens are critical for successful clinical resolution of sporotrichosis in both cats and humans. Species-level identification of Sporothrix is possible with molecular diagnostics and necessary for tracking the geographic expansion of S. brasiliensis and better understanding its epidemiology. Combatting cat-transmitted sporotrichosis requires a One Health approach to successfully implement public health control measures. |
Detection and control of fungal outbreaks
Caceres DH , Mohd Tap R , Alastruey-Izquierdo A , Hagen F . Mycopathologia 2020 185 (5) 741-745 The fungal kingdom contains an estimated 2.2–3.8 million species [1]. Fungi are ubiquitous and primarily co-exist with plants and animals, creating mutual benefits, including the acquisition of vital nutrients and protection from pathogenic microorganisms. Generally, fungi are beneficial to humankind and are indispensable in the food production chain and in biotechnological processes like the production of chemical compounds and drugs. Approximately 600 species have been reported to cause human disease, mostly due to traumatic introduction into the host. An even smaller number cause serious superficial or invasive disease (https://www.clinicalfungi.org/). The dermatophytes cause superficial infections, but also deep infections, and negatively impact the quality of life of ~ 1 billion people worldwide [2–5]. Globally, Aspergillus, Candida, Cryptococcus, Pneumocystis, and Mucorales infections (the ‘big five’) are important causes of fungal morbidity and mortality, primarily affecting immunocompromised hosts [2, 6, 7]. Among these big five, Candida yeasts cause the largest number of infections, with annual estimates of 134 million mucosal infections, as well as 750,000 life-threatening bloodstream infections associated with mortality rates > 40% [2, 8]. |
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. |
Understanding the Emergence of Multidrug-Resistant Candida : Using Whole-Genome Sequencing to Describe the Population Structure of Candida haemulonii Species Complex.
Gade L , Munoz JF , Sheth M , Wagner D , Berkow EL , Forsberg K , Jackson BR , Ramos-Castro R , Escandon P , Dolande M , Ben-Ami R , Espinosa-Bode A , Caceres DH , Lockhart SR , Cuomo CA , Litvintseva AP . Front Genet 2020 11 554 The recent emergence of a multidrug-resistant yeast, Candida auris, has drawn attention to the closely related species from the Candida haemulonii complex that include C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii, and the recently identified Candida vulturna. Here, we used antifungal susceptibility testing and whole-genome sequencing (WGS) to investigate drug resistance and genetic diversity among isolates of C. haemulonii complex from different geographic areas in order to assess population structure and the extent of clonality among strains. Although most isolates of all four species were genetically distinct, we detected evidence of the in-hospital transmission of C. haemulonii and C. duobushaemulonii in one hospital in Panama, indicating that these species are also capable of causing outbreaks in healthcare settings. We also detected evidence of the rising azole resistance among isolates of C. haemulonii and C. duobushaemulonii in Colombia, Panama, and Venezuela linked to substitutions in ERG11 gene as well as amplification of this gene in C. haemulonii in isolates in Colombia suggesting the presence of evolutionary pressure for developing azole resistance in this region. Our results demonstrate that these species need to be monitored as possible causes of outbreaks of invasive infection. |
Innovative approaches for Histoplasma detection
Caceres DH , Fernandez NB , Lockhart SR . Curr Fungal Infect Rep 2020 14 (3) 310-316 Purpose of Review: This review highlights innovative approaches for histoplasmosis detection using laboratory technologies published in the past 6 years. Recent Findings: Microscopy and culture are the gold standards for confirming the diagnosis of histoplasmosis, but these can be slow, and their sensitivity and specificity can vary. It is well known that rapid diagnosis is necessary to save lives. Newer technologies based on detection of antibodies, antigens, and DNA can enable rapid and accurate clinical diagnosis. Summary: Based on a systematic review of the literature and evaluation of methodologies in five areas, assay accuracy, rapid testing, point of care testing, commercial availability, and use in animal diagnosis and environmental detection, we describe innovative approaches for detection of Histoplasma/histoplasmosis. |
Immunodiagnostic assays for the investigation of fungal outbreaks
Caceres DH , Chiller T , Lindsley MD . Mycopathologia 2020 185 (5) 867-880 Fungal pathogens can affect humans, animals, and plants, and they can be found in the environment or as part of the host microbiome. Fungal diseases present a broad clinical spectrum, ranging from superficial to invasive infections, and can cause outbreaks. During an outbreak investigation, the laboratory plays an essential role in verifying the diagnosis and helping to confirm the source of the outbreak. Immunodiagnostic assays are important tools and often relied upon for the diagnosis of fungal infections, since the gold standard assays of culture and histopathology are time-consuming and often require invasive procedures. Immunodiagnostic assays range from complement fixation and immunodiffusion to enzyme immunoassays and, most recently, to point-of-care lateral flow devices. In general, these assays provide results faster and offer good analytical performance. These characteristics make immunodiagnostic assays good laboratory tools for outbreak investigations. The aim of this review is to describe the principles, advantages, limitations, and availability of immunodiagnostics assays in outbreak investigations, based on the experience of a reference laboratory. |
Bloodstream infections with Candida auris among children in Colombia: Clinical characteristics and outcomes of 34 cases
Berrio I , Caceres DH , Coronell RW , Salcedo S , Mora L , Marin A , Varon C , Lockhart SR , Escandon P , Berkow EL , Rivera S , Chiller T , Vallabhaneni S . J Pediatric Infect Dis Soc 2020 10 (2) 151-154 BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. Here, we describe 34 cases of pediatric C. auris bloodstream infections (BSIs) identified during July 2014-October 2017 in 2 hospitals in Colombia. METHODS: We conducted a retrospective review of microbiology records for possible C. auris cases in 2 hospitals in Barranquilla and Cartagena. BSIs that occurred in patients aged <18 years confirmed as C. auris were included in this analysis. RESULTS: We identified 34 children with C. auris BSIs. Twenty-two (65%) patients were male, 21% were aged <28 days, 47% were aged 29-365 days, and 32% were aged >1 year. Underlying conditions included preterm birth (26%), being malnourished (59%), cancer (12%), solid-organ transplant (3%), and renal disease (3%). Eighty-two percent had a central venous catheter (CVC), 82% were on respiratory support, 56% received total parenteral nutrition (TPN), 15% had a surgical procedure, and 9% received hemodialysis. Preinfection inpatient stay was 22 days (interquartile range, 19-33 days), and in-hospital mortality was 41%. CONCLUSIONS: Candida auris affects children with a variety of medical conditions including prematurity and malignancy, as well as children with CVCs and those who receive TPN. Mortality was high, with nearly half of patients dying before discharge. However, unlike most other Candida species, C. auris can be transmitted in healthcare settings, as suggested by the close clustering of cases in time at each of the hospitals.Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. This report describes 34 cases of pediatric C. auris bloodstream infections, identified in two hospitals in Colombia, South America. |
Frequency of invasive fungal disease in adults: Experience of a specialized laboratory in Medellin, Colombia (2009-2015)
Valencia Y , Caceres DH , de Bedout C , Cano LE , Restrepo A . J Fungi (Basel) 2020 6 (1) Invasive fungal diseases (IFD) contribute significantly to worldwide morbidity and mortality, but their frequency is not well-described in some countries. The present work describes the frequency of IFD in a specialized laboratory in Colombia. A retrospective, descriptive study was implemented between March 2009 and December 2015. Results: 13,071 patients with clinical suspicion of IFD were referred during the study period, from which 33,516 biological samples were processed and analyzed using 14 laboratory methods. Diagnosis was confirmed in 1425 patients (11%), distributed according to the mycoses of interest analyzed here: histoplasmosis in 641/11,756 patients (6%), aspergillosis in 331/10,985 patients (3%), cryptococcosis in 239/8172 patients (3%), pneumocystosis in 111/1651 patients (7%), paracoccidioidomycosis in 60/10,178 patients (0.6%), and invasive candidiasis in 48/7525 patients (0.6%). From the first year of the study period to the last year, there was a 53% increase in the number of cases of IFD diagnosed. Our laboratory experienced a high frequency of IFD diagnosis, possibly attributable to the availability of a greater range of diagnostic tools. Frequency of IFD in this study was atypical compared with other studies, probably as a result of the single laboratory-site analysis. This demonstrates that implementing educational strategies helps to create a high index of clinical suspicion, while the availability and utilization of appropriate diagnostic assays assure greater reliability in identification of these cases. |
The Manaus Declaration: Current Situation of Histoplasmosis in the Americas, Report of the II Regional Meeting of the International Histoplasmosis Advocacy Group
Caceres DH , Adenis A , de Souza JVB , Gomez BL , Cruz KS , Pasqualotto AC , Ravasi G , Perez F , Chiller T , de Lacerda MVG , Nacher M . Curr Fungal Infect Rep 2019 13 (4) 244-249 Purpose of Review: The aim of this report is to summarize the conclusions of the II Regional Meeting on Histoplasmosis in the Americas held in Manaus, Brazil, on March 22–24, 2019. Recent Findings: Persons living with advanced HIV are at high risk for developing histoplasmosis. Clinical signs and symptoms of this disease are often non-specific, making it difficult to establish a diagnosis. Although with the recent technological advances, in vitro diagnostics and medicines for histoplasmosis are often not available in many regions around the world. In addition, histoplasmosis is often not included in HIV care and treatment programs, resulting in inadequate health system planning and missed opportunities to save lives. Summary: The II Regional Meeting on Histoplasmosis in the Americas gathered a multidisciplinary audience. Developed recommendations to be included in the WHO guidelines for diagnosis and treatment of histoplasmosis in advanced HIV were the product of this meeting, and guidelines are aimed to be published in early 2020. |
Candida auris: A review of recommendations for detection and control in healthcare settings
Caceres DH , Forsberg K , Welsh RM , Sexton DJ , Lockhart SR , Jackson BR , Chiller T . J Fungi (Basel) 2019 5 (4) Candida auris is an emerging multidrug-resistant fungal pathogen. Since first reported in 2009, C. auris has caused healthcare outbreaks around the world, often involving high mortality. Identification of C. auris has been a major challenge as many common conventional laboratory methods cannot accurately detect it. Early detection and implementation of infection control practices can prevent its spread. The aim of this review is to describe recommendations for the detection and control of C. auris in healthcare settings. |
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. |
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. |
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