Current Concepts in the Epidemiology, Diagnosis, and Management of Histoplasmosis Syndromes

Marwan M. Azar, MD; James L. Loyd, MD; Ryan F. Relich, PhD; L. Joseph Wheat, MD; Chadi A. Hage, MD


Semin Respir Crit Care Med. 2020;41(1):13-30. 

In This Article


Histoplasmosis is a global disease endemic to regions of all six inhabited continents. In North America, the areas of highest endemicity lie within the Mississippi and Ohio River Valleys of the central and eastern United States.[1] In areas surrounding these basins, the incidence of histoplasmosis is an estimated to be 6.1 cases per 100,000 and up to 90% of the population have been exposed to Histoplasma capsulatum in their lifetime.[2,3] Beyond the continental United States, Puerto Rico is moderately endemic for H. capsulatum and a recognized site of outbreaks.[4] Additionally, autochthonous cases of histoplasmosis related to point environmental sources have been reported in many regions of the United States not previously considered endemic, including the Rocky Mountain states (Montana and Idaho),[5] the southeast (Florida, South Carolina), the northeast (New York), and the North Central states (Minnesota, North Dakota).[4] In an era of mass travel and increased connectivity, imported cases of histoplasmosis are increasingly common. In states that border the eastern United States, including Connecticut,[6] New York,[7] and Georgia,[8] travel to Puerto Rico and to Caribbean countries appears to be a more common risk factor than travel to the Midwestern United States. Conditions suitable for H. capsulatum have migrated northwards in the past decade, likely as a result of climate change and anthropogenic land utilization.[9] Histoplasmosis-related hospitalizations have increased over the past decade throughout the United States and are increasingly seen in patients with immunocompromising conditions other than human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).[10]

Many areas of Latin America[11,12] including Brazil,[13,14] French Guiana,[15] Argentina,[16] Colombia,[17] Venezuela,[18] Guatemala,[19] and Panama[20] are highly endemic for histoplasmosis. In parts of Brazil, seroepidemiologic studies have indicated that up to 90% of the population have been exposed to H. capsulatum.[11] The epidemiology of histoplasmosis in South America has been highlighted by the advent of the AIDS epidemic. Progressive disseminated histoplasmosis (PDH) is the most common AIDS-defining illness in French Guiana, accounting for 41% of febrile hospitalized patients with AIDS,[15] while in Columbia 70% of patients with histoplasmosis from 1992 to 2008 had HIV/AIDS.[21] Histoplasmosis is rare in Europe except when acquired in other endemic areas,[22,23] though some autochthonous cases have been reported in Italy.[24] Parts of the Caribbean including Trinidad, Guyana, Barbados, and the Dominican Republic are also endemic.[25] In Trinidad, histoplasmin positivity may be up to 60% in individuals under the age of 60.

Histoplasmin skin test reactivity in China ranges from 6 to 50%.[26] Most cases occur in provinces along the Yangtze River where the majority of cases from a large 2013 outbreak were reported.[27] In Thailand, the AIDS epidemic has been linked to a spike in cases of PDH, with more than 1,200 cases reported between 1984 and 2010.[28,29] Though histoplasmin skin test positivity was reported at 26% in the Philippines,[30] there are few published cases of histoplasmosis, possibly a result of under-reporting or under-recognition.[31] H. capsulatum is endemic in parts of the Indian subcontinent, especially within the West Bengal and Uttar Pradesh states of Northeastern India.[32] Cases have also been reported in Bangladesh, Nepal, Pakistan, and Sri Lanka among others.[32]

African histoplasmosis, caused by H. capsulatum var. duboisii, occurs exclusively in Africa, particularly in Central and Western Africa and the island of Madagascar and coexists with the more common variety in parts of the continent. Most cases of H. capsulatum var. duboisii have been reported from Nigeria, Niger, Senegal, The Democratic Republic of Congo, Zaire, and Uganda,[33] whereas H. capsulatum var. capsulatum is endemic in Tanzania,[34] Zimbabwe,[35] and South Africa,[36] and occurs sporadically across the continent.[37]

In a recent systematic review of the literature that included 814 immunocompetent travelers who contracted histoplasmosis, the most common travel destination was South and Central America (57%) followed by North America (21%), and the most common risk factor was spelunking or exposure to bat guano (61%).[38] In areas not traditionally known to be endemic, rates of histoplasmosis-specific testing are low, contributing to diagnostic delay and worse outcomes.[6,39]