Histoplasmosis and tuberculosis (TB) are endemic in Central America and are the two most common opportunistic infections in HIV-infected patients. Despite the introduction of antiretroviral therapy in the region, morbidity and mortality associated with histoplasmosis and TB remain high due to late presentation to care and diagnostic delays. In the absence of rapid diagnostics, histoplasmosis is difficult to distinguish from TB, given overlapping risks and clinical presentation. Culture-based diagnostics for histoplasmosis and TB take week and are not available in most primary care centers. Because of significant drug interactions between the azoles, rifamycins, and antiretroviral therapy, treatment for histoplasmosis in HIV-infected patients with clinical febrile syndromes is usually administered only after failure of initial TB therapy. Rapid diagnosis of histoplasmosis in febrile HIV-infected patients would facilitate clinical management and outcomes by allowing rapid distinction from TB and expediting initiation of antifungal therapy.
The aim of this application is to develop a point-of-care diagnostic device for histoplasmosis that could be used in resource-limited settings, including rural primary care settings without extensive laboratory capabilities. To this end, we have established a cohort of Panamanian AIDS patients through a collaboration with the Instituto Conmemorativo Gorgas de Estudios de la Salud (ICGES), which has ties to all major hospitals in Panama and a distinguished track record in research and education. A longitudinal study will be performed to describe the epidemiology and outcomes of HIVinfected patients diagnosed with PDH and TB, and to facilitate development of a urinary point-of-care diagnostic test for histoplasmosis. Our laboratory has a platform for the development of point-of-care diagnostic tests for invasive fungal infections using enzyme immunoassays mounted on lateral flow device technology. A prototype assay was successfully developed in our laboratory for the detection of Aspergillus antigens. A similar methodology will be applied to the development of a point-of-care diagnostic device for histoplasmosis, using a well characterized and clinically validated polyclonal antibody that detects H. capsulatum in urine samples. Development of a non-invasive, low cost point-of-care that does not require sophisticated laboratory processing would greatly improve diagnostic and treatment algorithms for febrile HIVinfected patients in Central America, particularly those living in remote or rural areas.
Histoplasmosis is a major cause of morbidity and mortality in HIV-infected patients in Central America. Currently available diagnostic modalities are slow and only available in specialized centers. HIV-infected patients with histoplasmosis are often undiagnosed, or diagnosed so late that their clinical outcomes are poor. In this application, we propose to develop a simple, lowcost point-of-care device for the diagnosis of histoplasmosis that will promote early and appropriate therapy.
