Monika Roy

Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries

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. Widely accepted treatment guidelines recommend amphotericin B and flucytosine as first-line induction treatment for cryptococcal meningitis. However, flucytosine is unavailable in Africa and most of Asia, and safe amphotericin B administration requires patient hospitalisation and careful laboratory monitoring to identify and treat common side-effects. Therefore, fluconazole monotherapy is widely used in low-income and middle-income countries for induction therapy, but treatment is associated with significantly increased rates of mortality. We review the antifungal drugs used to treat cryptococcal meningitis with respect to clinical effectiveness and access issues specific to low-income and middle-income countries. Each drug poses unique access challenges: amphotericin B through cost, toxic effects, and insufficiently coordinated distribution; flucytosine through cost and scarcity of registration; and fluconazole through challenges in maintenance of local stocks--eg, sustainability of donations or insufficient generic supplies. We advocate ten steps that need to be taken to improve access to safe and effective antifungal therapy for cryptococcal meningitis.

Clinical findings for fungal infections caused by methylprednisolone injections.

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 outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections. METHODS We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification. RESULTS Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis. CONCLUSIONS The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).

Disseminated histoplasmosis in HIV-infected patients in South America: a neglected killer continues on its rampage.

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; however, they overlook the exact cause of death. In the context of the South American pathogen ecology, the systemic mycosis due to Histoplasma capsulatum var. capsulatum is probably on the top of the list of AIDS-defining illnesses and AIDS-related deaths [1], yet it is mostly undiagnosed and is not even on the diagnostic algorithm used by a significant proportion of clinicians facing a febrile, severely immunodepressed patient in the region.

Preventing deaths from cryptococcal meningitis: from bench to bedside

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 early. Screening persons with HIV for cryptococcal infection when they access healthcare can identify asymptomatic infected patients allowing for prompt treatment and prevention of death. A newly developed point-of-care assay for cryptococcal antigen, as well as growing evidence supporting the utility and cost–effectiveness of screening, are further reasons to consider broad implementation of cryptococcal screening in countries with a high burden of cryptococcal disease.

Evaluation of screening and treatment of cryptococcal antigenaemia among HIV‐infected persons in Soweto, South Africa

We retrospectively evaluated clinic‐based screening to determine the prevalence of cryptococcal antigenaemia and management and outcome of patients with antigenaemia.

Epidemiologic and Ecologic Features of Blastomycosis: A Review

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, the epidemiologic features of disease are not as clearly defined as those of other endemic mycoses, such as histoplasmosis and coccidioidomycosis. We review the ecologic and epidemiologic aspects of B. dermatitidis and blastomycosis, including geographic distribution, environmental niche, seasonality, and possible risk factors.

Aflatoxin contamination in food commodities in Bangladesh

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 three cities in Bangladesh. We quantified aflatoxin levels from pooled subsamples using fluorescence high-performance liquid chromatography. Aflatoxin levels were highest in dates and groundnuts (maximum 623 and 423 ng/g), respectively. Samples of betelnut (mean 30.6 ng/g), lentils (mean 21.2 ng/g) and red chili powder (>20 ng/g) also had elevated levels. The mean aflatoxin level among poultry feed samples was 73.0 ng/g. Aflatoxin levels were above the US maximum regulatory levels of 20 ng/g in five of eight commonly ingested human food commodities tested.

High Mortality and Coinfection in a Prospective Cohort of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patients with Histoplasmosis in Guatemala.

Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients ≥ 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria. A confirmed case of histoplasmosis was defined as a person with a positive culture or urine antigen test for Histoplasma capsulatum. Demographic and clinical data were also collected and analyzed. Of 263 enrolled as suspected cases of histoplasmosis, 101 (38.4%) were confirmed cases. Median time to diagnosis was 15 days after presentation (interquartile range [IQR] = 5-23). Crude overall mortality was 43.6%; median survival time was 19 days (IQR = 4-69). Mycobacterial infection was diagnosed in 70 (26.6%) cases; 26 (25.7%) histoplasmosis cases were coinfected with mycobacteria. High mortality and short survival time after initial symptoms were observed in patients with histoplasmosis. Mycobacterial coinfection diagnoses were frequent, highlighting the importance of pursuing diagnoses for both diseases.

Understanding Sustained Retention in HIV/AIDS Care and Treatment: a Synthetic Review

Sustained retention represents an enduring and evolving challenge to HIV treatment programs in Africa. We present a theoretical framework for sustained retention borrowing from ecologic principles of sustainability and dynamic adaptation. We posit that sustained retention from the patient perspective is dependent on three foundational principles: (1) patient activation: the acceptance, prioritization, literacy, and skills to manage a chronic disease condition, (2) social normalization: the engagement of a social network and harnessing social capital to support care and treatment, and (3) livelihood routinization: the integration of care and treatment activities into livelihood priorities that may change over time. Using this framework, we highlight barriers specific to sustained retention and review interventions addressing long-term, sustained retention in HIV care with a focus on Sub-Saharan Africa.

Trichosporon asahii among intensive care unit patients at a medical center in Jamaica.

We investigated an increase in Trichosporon asahii isolates among inpatients. We identified 63 cases; 4 involved disseminated disease. Trichosporon species was recovered from equipment cleaning rooms, washbasins, and fomites, which suggests transmission through washbasins. Patient washbasins should be single-patient use only; adherence to appropriate hospital disinfection guidelines was recommended.