Advances in the Diagnosis of Histoplasmosis: An Update into the Laboratory Diagnosis of Histoplasma capsulatum

AGUSTINA TOSCANINI; RODRÍGUEZ LABOCCETTA, CAROLINA; VIDELA GARRIDO, AGUSTÍN; FERNÁNDEZ, VÍCTOR J BRICEÑO; ALAVA, KATHERINE HERMIDA; ETCHECOPAZ, ALEJANDRO; CRISTINA A. IOVANNITTI; A. D. NUSBLAT; CUESTAS MARIA LUJAN

Histoplasmosis: From Diagnosis to Treatment

Nova

Año: 2023; p. 45 - 97

Histoplasmosis is a life-threatening systemic infection caused by the thermally dimorphic fungal pathogen Histoplasma capsulatum, whose natural reservoirs are thought to be soil enriched with bird excreta and bat guano. Althought this disease is highly endemic in the Americas, it has a worldwide distribution. Among immunocompetent individuals, histoplasmosis is mostly asymptomatic and spontaneously self-limited. However, histoplasmosis is responsible for important morbidity and mortality in patients with an acquired or congenital T cellular immunity deficiency. In HIV-infected patients, its extrapulmonary or disseminated form, known as progressive disseminated histoplasmosis (PDH), is an AIDS-defining illness, particularly in Latin America, where 15,000 new infections and 9,000 deaths are estimated to occur annually.Histoplasmosis diagnosis is still challenging since symptoms are nonspecific and may be confused with other infections, particularly tuberculosis. Moreover, late diagnosis of PDH is associated with high mortality; thus, there is a major need for a rapid diagnosis and the instauration of an appropriate pharmacological therapy. In this regard, some progress has been recently achieved, such as the publication of World Health Organization (WHO)/Pan American Health Organization guidelines for the diagnosis and management of PDH among patients living with HIV and the inclusion of Histoplasma antigen testing in the WHO list of Essential Diagnostics.Definitive diagnosis of histoplasmosis is achieved by culture and histopathology, but these methods present some drawbacks, including limited sensitivity, the need for biosafety level-3 laboratories, trained mycologysts, and a long turnaround time of up to several weeks for fungal isolation. The use of serologic assays for PDH diagnosis is limited by a low sensitivity in immunocompromised individuals. Despite some in-house DNA detection assays were developed and showed a satisfactory performance for diagnosis, all of them lack proper standardization and validation. Diagnosis of PDH by detecting urine Histoplasma antigen has proven to be highly useful due to its high sensitivity. However, cross-reactivity with other related fungi is common with the currently available commercial tests. Moreover, these tests are expensive and only performed in a few laboratories. The identification of novel protein candidates and their recombinant production may offer high-quality reagents that cirvunvect the use of native antigens. The aim of this chapter is to describe the utility and drawbacks of the available diagnostic methods for histoplasmosis, and to review the latest approaches to achieve rapid and accurate tests for diagnosing this fungal disease