Tom M Chiller

• Centers for Disease Control and Prevention

Cryptococcal antigen (CrAg) detection could direct timely initiation of antifungal therapy. We searched MEDLINE and EMBASE for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on HIV-positive adults with suspected cryptococcal meningitis (CM). With QUADAS-2, we evaluated risk of bias (RoB) of 11 inclu...

Background In August 2018, New York City health authorities notified CDC of two students with pneumonia and rash following mission trips to Mexico. Send-out Coccidioides serology tests took 7 days for results to return. Both students and five additional travelers from four states were diagnosed with coccidioidomycosis. A seroepidemiologic survey im...

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 MiraVi...

Background: Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods: We sampled patients, pati...

Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect Histoplasma capsulatum infection in endemic regions would dramatically decrease...

Background: Most studies of post-transplant CMV infection have focused on either solid organ or hematopoietic cell transplant (HCT) recipients. A large prospective cohort study involving both lung and HCT recipients provided an opportunity to compare the epidemiology and outcomes of CMV infections in these two groups. Methods: Patients were foll...

Introduction: Candida is a leading cause of healthcare-associated bloodstream infections in the United States. Infants and children have unique risk factors for candidemia, and the Candida species distribution in this group is different that among adults; however, candidemia epidemiology in this population has not been described recently. Methods...

Background: Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevale...

Background: Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. Methods: We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were...

The emergence of Cryptococcus gattii, previously regarded as a predominantly tropical pathogen, in the temperate climate of the North American Pacific Northwest (PNW) in 1999 prompted several questions. The most prevalent among these was the timing of the introduction of this pathogen to this novel environment. Here, we infer tip-dated timing estim...

A total of 23/45 (51%) patients with AIDS and histoplasmosis from Medellín, Colombia had other infections. Tuberculosis was the most common (n = 16/23, 70%). Pneumocystosis and cryptococcosis were found in three patients each (13%), bacterial infection and cytomegalovirus occurred each in two patients (9%) while toxoplasmosis, herpes virus and esop...

Infections caused by pan-azole-resistant Aspergillus fumigatus strains have emerged in Europe and recently in the United States. Physicians specializing in infectious diseases reported observing pan-azole-resistant infections and low rates of susceptibility testing, suggesting the need for wider-scale testing.

Histoplasmosis is considered one of the most important endemic and systemic mycoses worldwide. Until now few molecular techniques have been developed for its diagnosis. The aim of this study was to develop and evaluate three real time PCR (qPCR) protocols for different protein-coding genes (100-kDa, H and M antigens) using an animal model. Fresh an...

Sequences from different H. capsulatum clades used for designing primers and probes used for 100-kDa protocol. The final choices of primer and probe sequences are shown highlighted in yellow and turquoise, respectively. (PDF)

Sequences from different H. capsulatum clades used for designing primers and probes used for M antigen protocol. The final choices of primer and probe sequences are shown highlighted in yellow and turquoise, respectively. (PDF)

Sequences from different H. capsulatum clades used for designing primers and probes used for H antigen protocol. The final choices of primer and probe sequences are shown highlighted in yellow and turquoise, respectively. (PDF)

A Lateral Flow Assay to detect cryptococcal antigen (CrAg® LFA) in serum and cerebrospinal fluid for the rapid diagnosis of cryptococcosis was evaluated. A retrospective validation was performed. Sensitivity and specificity of the CrAg® LFA was 100%. High concordance (kappa index=1.0) between Cryptococcal Antigen Latex Agglutination System (CALAS®)...

Exophiala (Wangiella) dermatitidis is a dematiaceous fungus that can grow in yeast or mold forms and is typically found in decaying organic matter. It can cause central nervous system disease, particularly in immunocompromised patients, and has been implicated as a respiratory pathogen in cystic fibrosis patients [1,2]. It has also been identified...

Background: High mortality rates among asymptomatic cryptococcal antigen (CrAg)-positive patients identified through CrAg screening, despite pre-emptive fluconazole, may be due to undiagnosed cryptococcal meningitis. Methods: Symptoms were reviewed in CrAg-positive patients identified through screening 19,233 individuals with CD4 cell counts < 1...

Candida auris is an emerging, multidrug-resistant yeast that can spread in healthcare settings. It can cause invasive infections with high mortality and is difficult to identify using traditional yeast identification methods. C. auris has been reported in over a dozen countries, and as of July 2017, 99 clinical cases have been reported in the Unite...

Background: Invasive candidiasis (IC) is a common cause of mortality in solid organ transplant recipients (OTRs), but knowledge of epidemiology in this population is limited. Method: The present analysis describes data from 15 US centers that prospectively identified IC from nearly 17,000 OTRs. Analyses were undertaken to determine predictors of...

During September 2012, CDC, in collaboration with state and local health departments and the Food and Drug Administration (FDA), investigated a multistate outbreak of fungal meningitis and other infections caused by injections of contaminated methylprednisolone acetate solution (MPA) (1). After this unprecedented outbreak, scientists in the CDC Myc...

Background: Candida glabrata (Cg) is the second most common cause of candidemia in the United States. Echinocandins are first-line treatment for Cg due to substantial resistance to azoles. Echinocandin resistance, concomitant with azole resistance, is concerning due to limited treatment options. We describe the epidemiology of echinocandin-resist...

We used real-time polymerase chain reaction and culture to demonstrate persistent colonization of soils by Coccidioides immitis, an agent of valley fever, in Washington State linked to recent human infections and located outside the endemic range. Whole-genome sequencing confirmed genetic identity between isolates from soil and one of the case-pati...

Health disparities in access to solid organ transplantation (SOT) and graft survival are well recognized, but there are limited data on the relationship of race to risk of invasive fungal infection (IFI) among SOT recipients. We conducted a case-control study using data from the Transplant-Associated Infection Surveillance Network (TRANSNET) to inv...

Cryptococcal meningitis (CM) is one of the leading opportunistic infections associated with human immunodeficiency virus (HIV) infection. The worldwide burden of CM among persons living with HIV/acquired immunodeficiency syndrome (AIDS) was estimated in 2009 to be 957,900 cases, with approximately 624,700 deaths annually. The high burden of CM glob...

We validated an antigen capture enzyme-linked immunosorbent assay (ELISA) in Colombian persons with AIDS and proven histoplasmosis and evaluated the correlation between antigenuria and clinical improvement during follow-up. The sensitivity of the Histoplasma capsulatum ELISA was 86%, and the overall specificity was 94%. The antigen test successfull...

Candida glabrata is the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of C. glabrata disease due to the high rate of resistance to fluconazole. Recent case reports indicate that C. glabrata resistance to echinocandins may be increasing. We perfo...

Mucormycosis is an invasive fungal infection with a high fatality rate. We investigated an outbreak of mucormycosis in a pediatric hospital to determine routes of pathogen transmission from the environment and prevent additional infections. A case was defined as a hospital-onset illness consistent with mucormycosis, confirmed by culture or histopat...

Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Netwo...

Background: The 2012 outbreak of fungal meningitis associated with contaminated methylprednisolone produced by a compounding pharmacy has resulted in >750 infections. An important question facing patients and clinicians is the duration of antifungal therapy. We evaluated (1-3)-β-d-glucan (BDG) as a marker for monitoring response to treatment. Met...

HIV/AIDS is not a neglected disease. Histoplasmosis is not considered a neglected disease in North America. However, in South America, it should be. It often affects neglected populations and represents a lethal blind spot of the HIV/AIDS data collection systems. Counts of new AIDS cases and AIDS-related deaths are useful to follow the epidemic; ho...

Introduction: The Global Foodborne Infections Network (GFN), launched in 2000, is a capacity building program designed to strengthen laboratory-based foodborne disease surveillance in resource-poor countries or regions. GFN is comprised of eleven institutional partners that provide both technical and financial support. In 2012, GFN coordinated the...

BACKGROUND Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant out...

Background: During 2012-2013, CDC and health departments responded to a large outbreak of fungal meningitis among persons injected with contaminated methylprednisolone acetate (MPA). Several public health actions were taken to limit the effects of contaminated MPA: prompt recall of MPA, notification of exposed persons, and clinician outreach to pro...

Clonal VGII subtypes (outbreak strains) of Cryptococcus gattii have caused an outbreak in the US Pacific Northwest since 2004. Outbreak-associated infections occur equally in male and female patients (median age 56 years) and usually cause pulmonary disease in persons with underlying medical conditions. Since 2009, a total of 25 C. gattii infection...

In September 2012, the Centers for Disease Control and Prevention (CDC) initiated an outbreak investigation of fungal infections linked to injection of contaminated methylprednisolone acetate (MPA). Between 2 October 2012 and 14 February 2013, the CDC laboratory received 799 fungal isolates or human specimens, including cerebrospinal fluid (CSF), s...

Six years after the first Society guidelines were published, cryptococcal meningitis (CM) remains an important cause of morbidity and mortality among HIV-infected adults in South Africa. Several important developments have spurred the publication of updated guidelines to manage this common fungal opportunistic infection. Recommendations described h...

Cryptococcal meningitis is the leading cause of adult meningitis in sub-Saharan Africa, and contributes up to 20% of AIDS-related mortality in low-income and middle-income countries every year. Antifungal treatment for cryptococcal meningitis relies on three old, off-patent antifungal drugs: amphotericin B deoxycholate, flucytosine, and fluconazole...

A previous study carried out in a tertiary care hospital in Colombia demonstrated the usefulness of the Cryptococcus capsular antigen detection by latex (CrAg Latex) in the early diagnosis of cryptococcosis in HIV-infected patients with low CD4 + levels. The aim of this study was to establish the performance of a new rapid lateral flow assay (CrAg...

Background: Salmonella is a major bacterial pathogen transmitted commonly through food. Increasing resistance to antimicrobial agents (e.g., ceftriaxone, ciprofloxacin) used to treat serious Salmonella infections threatens the utility of these agents. Infection with antimicrobial-resistant Salmonella has been associated with increased risk of seve...

In this issue of Antimicrobial Agents and Chemotherapy, Stevens offers his reflections on the therapeutic approach to the ongoing outbreak of Exserohilum infections related to contaminated methylprednisolone injections (1).…

Clinical, laboratory, and epidemiologic evidence suggest that 3 individuals with acute coccidioidomycosis were exposed in Washington State, significantly beyond previously identified endemic areas. Given the patients’ lack of recent travel, coccidioidomycosis was not suspected, leading to delays in diagnosis and appropriate therapy. Clinicians shou...

In South Africa, the incidence of HIV-associated cryptococcal meningitis remains high despite the increased coverage of antiretroviral treatment, and in routine care settings, the disease is associated with a case-fatality ratio of more than 50%. Laboratory-based screening and pre-emptive antifungal treatment of cryptococcal disease have been sugge...

Blastomycosis is a potentially fatal infection caused by Blastomyces dermatitidis, a fungus endemic to North America in areas surrounding the Ohio and Mississippi River valleys and the Great Lakes. The clinical manifestations, diagnostic techniques, and treatment strategies for blastomycosis are relatively well-described in the literature; however,...

Background: Candida BSI complicated by IE may require cardiac valve replacement and has high mortality. Routine echocardiography for patients with Candida BSI is not currently recommended. There are few data defining the proportion of patients with Candida BSI who have echocardiography performed and who develop IE. Methods: Candida BSIs in reside...

Background: Renal failure and hemodialysis (HD) predispose patients to candidemia, and the risk of this infection rises when central venous catheters (CVCs) are used for HD vascular access. To explore the epidemiology of candidemia with recent HD, we compared them with candidemia cases not on HD and with the overall surveillance area HD cohort. M...

Background: Ocular candidiasis requires aggressive therapy to prevent vision loss. Recent studies suggest that earlier diagnosis and treatment of Candida BSIs has lowered the proportion with ocular involvement, possibly precluding the need for routine DFE. The Infectious Diseases Society of America recommends DFE within 1 week for patients with Can...

Infections caused by Histoplasma capsulatum are found most often in endemic regions of North, Central, and South America. H. capsulatum has been divided into eight geographic clades by multi-locus sequence typing (MLST). Recently, one isolate and five formalin-fixed paraffin-embedded (FFPE) tissue samples were received from six of 15 suspected case...

HIV-associated cryptococcal meningitis (CM) is estimated to cause over half a million deaths annually in Africa. Many of these deaths are preventable. Screening patients for subclinical cryptococcal infection at the time of entry into antiretroviral therapy programs using cryptococcal antigen (CRAG) immunoassays is highly effective in identifying p...

Acremonium species cause a variety of human infections, while Lecanicillium species have not been reported as human pathogens. We describe a pseudo-outbreak involving both organisms, highlighting the role and limitations of molecular methods in the characterization of rare fungal isolates. Repeated isolation of these fungi from patient tissue sampl...

Background: Candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported. Methods: We conducted active, population-based surveillance in metropolitan Atlanta, Georgia, and Baltimore City/County, Maryland (combined population 5.2 million), during 2008-2011. We calculated...

During September 2009, we performed a rapid cross-sectional study to investigate the extent of aflatoxin contamination among common Bangladeshi foods. We collected eight common human food commodities (rice, lentils, wheat flour, dates, betelnut, red chili powder, ginger and groundnuts) and poultry feed samples from two large markets in each of thre...

Between 2008 and 2011, population-based candidemia surveillance was conducted in Atlanta, GA, and Baltimore, MD. Surveillance had been previously performed in Atlanta in 1992 to 1993 and in Baltimore in 1998 to 2000, making this the first population-based candidemia surveillance conducted over multiple time points in the United States. From 2,675 i...

To assess trends in incidence of Candida spp. central line-associated bloodstream infections (CLABSIs) in US NICUs, 1999-2009. Data from NICUs participating in the National Nosocomial Infections Surveillance (1999-2004) and National Healthcare Safety Network (2006-2009) were analyzed. Overall and birth weight-specific incidence rates of Candida spp...

The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases ident...

TO THE EDITOR: An outbreak of Cryptococcus gattii cryptococcosis has been ongoing in the US Pacific Northwest (PNW) since 1999 (1-3). In contrast to C. neoformans infections, which typically cause meningitis in HIV-infected persons, outbreak-associated C. gattii infections occur primarily in persons without HIV and often cause pneumonia (1-3). Spor...

Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus species, is one of the most common opportunistic infections among persons with HIV/AIDS. The highest burden of disease is in sub-Saharan Africa and Southeast Asia, where limited access to antiretroviral treatment and appropriate antifungal therapy contributes to high mortality ra...

Cryptococcus gattii (Cg) has caused increasing infections in the US Pacific Northwest (PNW) since 2004. We describe this outbreak and compare clinical aspects of infection in the United States among patients infected with different Cg genotypes. Beginning in 2005, PNW state health departments conducted retrospective and prospective passive surveill...

The epidemiology of systemic fungal diseases has evolved rapidly over the past 2 decades. Advances in medical treatment have led to improved survival in the general population, but these advances have also led to larger numbers of individuals (including those who have indwelling catheters, who are in intensive care, who have received various immuno...

Background: Infection (IFX) is a major cause of morbidity and mortality after HSCT. To define better the epidemiology, risk factors and outcomes of infections after HSCT , we conducted a prospective, multicenter cohort study of HSCT recipients from 2006-2011. Methods: 6 US transplant centers followed HSCT recipients for 30 months. Data were p...

Mucormycosis has been reported to be occurring more frequently in hematopoietic stem cell transplant (HSCT) recipients in recent years. We investigated a hospital cluster of mucormycosis cases among patients with hematologic disorders. Case-patients were identified through hospital microbiology and pathology database searches and compared to random...

Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus spp., is the most common form of meningitis and a leading cause of death among persons with HIV/AIDS in sub-Saharan Africa. Detection of cryptococcal antigen, which is present several weeks before overt signs of meningitis develop, provides an opportunity to detect infection earl...

Between December 2007 and July 2008, three neonates in a neonatal intensive care unit (NICU) in Salford, UK, were diagnosed with primary cutaneous aspergillosis (PCA) due to Aspergillus fumigatus. The first PCA case, in December 2007, developed multi-organ failure leading to death within a short time frame: the other two cases survived after treatm...

Cryptococcosis is a common opportunistic infection of human immunodeficiency virus (HIV)-infected individuals mostly occurring in resource-limited countries. This study compares the performance of a recently developed lateral flow immunoassay (LFA) to blood culture and enzyme immunoassay (EIA) for the diagnosis of cryptococcosis. Archived sera from...

We determined the echinocandin minimum effective concentration (MEC) values for caspofungin, micafungin, and anidulafungin against 288 Aspergillus isolates prospectively collected from transplant patients with proven or probable invasive aspergillosis between 2001 and 2006 as part of the Transplant-Associated Infection Surveillance Network (TRANSNE...

Invasive fungal infections (IFI) are a major cause of morbidity and mortality among both solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Candida is the most common cause of IFI in SOT recipients and the second most common cause of IFI in HSCT recipients. We determined susceptibilities to fluconazole, voriconaz...