Cutaneous Manifestations of Infection by Free-Living Amebas

Introduction

Free-living amebas are mitochondria-bearing eukaryotic protozoa that cause fatal central nervous system (CNS) disease in humans and other animals. Species known to cause the disease include Naegleria , Acanthamoeba , Balamuthia , and Sappinia . These amebas are also called amphizoic amebas, because of their ability to lead a free-living existence in nature as well as lead an endozoic existence within humans and other animals. Acanthamoeba and Naegleria are ubiquitous and have been isolated from all continents. They are usually found in soil or in fresh water such as ponds, creeks, and pools.

N. fowleri causes a fulminating and acute necrotizing meningoencephalitis called primary amebic meningoencephalitis (PAM), primarily in healthy children and young adults, leading to death within 5–10 days. Populations at risk are those with a history of swimming in warm freshwater bodies such as lakes, ponds, hot springs, and effluents from factories and power plants.

Acanthamoeba , on the other hand, causes an insidious subacute encephalitis, referred to by some as granulomatous amebic encephalitis (GAE). Based on rRNA sequences, the whole genus Acanthamoeba is divided into 17 genotypes. The affected individuals may or may not have a history of exposure to natural bodies of water, but in many cases they have a history of immunodeficiency, whether because of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), or debilitation, immuno­suppressive drugs, or pregnancy. Occasionally, patients with Acanthamoeba infections have skin lesions, commonly described as chronic ulcers. GAE also leads to death after a prolonged course of several weeks to years.

Up until 1990 all GAE infections were considered to be due to Acanthamoeba because of the presence of cysts in the brain tissue, since N. fowleri does not encyst in the brain. However, many of these cases were considered atypical because they were serologically negative in the immunofluorescence (IIF) test for N. fowleri and Acanthamoeba spp. In 1990, Visvesvara and Stehr-Green reported the isolation of a new species of ameba, provisionally identified as leptomyxid ameba, from the brain of a pregnant baboon at the San Diego Zoo that had died after developing lethargy and focal neurologic deficits. Visvesvara et al. made antiserum to this ameba and demonstrated, using the IIF test on a series of 16 atypical cases of GAE from different parts of the world (including two from Peru), that most of these cases were caused by the leptomyxid ameba. Five of these 16 cases also manifested cutaneous ulcers. By 1993, Vivesvara et al. had established the characteristic features of this new ameba species and named it Balamuthia mandrillaris .

B. mandrillaris is now considered an emerging cause of amebic meningoencephalitis around the world. In most cases, the disease follows a prolonged course with a fatal outcome; commonly the diagnosis is either missed or made only postmortem. Skin lesions, whenever present, precede the development of the CNS symptoms by weeks or months. Therefore it is important for dermatologist and specialist alike to recognize cutaneous involvement at an early stage.

Epidemiology

Around 200 cases of B. mandrillaris infection (BMI) have been reported worldwide, with the highest numbers reported in the American continent, including the USA and various South American countries including Peru, Mexico, Venezuela, Argentina, Brazil, and Chile. The disease has also been reported in Asia, Australia, and Europe. Whereas some cases have taken place in the context of immunosuppression, most cases are seen among immune-competent patients. It is interesting to remark that a high percentage (5%) of the USA cases reported to the Centers for Disease Control and Prevention (CDC) for Balamuthia testing had Hispanic ethnicity; 55% have been reported to be less than 15 years of age.

Most remarkably, a 2010 report has described the occurrence of two cohorts of BMI in the recipients of different organ transplants from two infected donors.

Naegleria and Acanthamoeba have been repeatedly isolated from nature. However, little is known about the ecology of B. mandrillaris . Most isolates have been made from clinical specimens, requiring tissue cultures. Balamuthia has been occasionally isolated from nature; it seems most likely an inhabitant of soil and water, with a special predilection for dusty, dry environments encircling green valleys, such as the Californian and Peruvian coasts. On two occasions B. mandrillaris has been isolated from the surroundings of patients' home areas: once in California and most recently in Peru.

The sporadic appearance of Balamuthia as a cause of human disease seems to indicate that the ameba is present in the human environment: this is also corroborated by the presence of antibodies against Balamuthia demonstrated in serologic surveys of otherwise-normal populations in the USA, Australia, and Africa. The frequency of Hispanic ethnicity in the Californian cases and the high incidence in Peru may point to genetic factors playing a role in the susceptibility to develop the infection.

Up to 55 cases of free-living ameba infection have been identified at the Instituto de Medicina Tropical Alexander von Humboldt, at Cayetano Heredia General Hospital, in Lima, Peru ; 20 cases have been confirmed by immunofluorescence testing as having been caused by Balamuthia .

Peruvian cases have originated from three coastal, semidesert regions such as Piura (north), Ica (south), and Lima (central coast). Many of these patients were children, mostly male, either farmers or urban dwellers. Frequent activities at risk of developing BMI include not only swimming in ponds, creeks and pools, but also home gardening, agricultural labor, desert motorbiking, and dirt-biking. There is an occasional history of trauma related to the site of the skin lesion.