Nervous System Diseases

Fungal and Protozoan Infections of the Nervous System

Fungal and Protozoan Diseases

Fungi and protozoa may cause nervous system diseases, and while they tend to be rare in developed regions, these diseases are often life-threatening, especially in immunocompromised populations.

Fungal nervous system diseases are rare in healthy individuals. Fungal meningitis may present in immunocompromised individuals, such as those with HIV. Species of Cryptococcus, Histoplasma, Blastomyces, and Coccidioides that are found in soils, possibly from bird or bat feces, are the causative agents of fungal meningitis. These fungi first infect the blood and are later spread to the central nervous system. Diagnosis is through cerebrospinal fluid testing. Antifungal medications, usually given over long periods while the patient remains hospitalized, are required to clear the infection.

Coccidioides immitis is a fungus that can cause infections in the lungs when spores are inhaled. An arthroconidium (plural, arthroconidia) is a spore that forms from the hypha of a fungus. In some cases arthroconidia from C. immitis have been found in the cerebrospinal fluid and brains of patients suffering infection. These spores can cause bleeding in the brain, leading to stroke.
Coccidioides immitis, a type of fungus, can lead to infection of the lungs when its arthroconidia, or spores, are inhaled. Arthroconidia of C. immitis have been found in the cerebrospinal fluid and brain tissue of patients with such an infection.
Credit: CDC
An amoeba, Naegleria fowleri, may also cause meningitis. The amoeba is found in warm fresh water, including in pools, spas, and hoses. Infection results when contaminated water makes its way up the nasal passages and the amoeba migrates to the brain. Amoebic meningitis has not yet been successfully treated in vivo—it has proven fatal in nearly every case, but there are promising studies using a drug called miltefosine. This drug works by interfering with the integrity and functioning of the amoeba mitochondria, the organelles that produce energy for the cells. Fortunately, despite the relative abundance of the amoeba in nature, infections are rare. The parasitic protozoan Toxoplasma gondii causes a condition known as toxoplasmosis. In people with normal immune function, this condition is so mild as to typically go unnoticed. In AIDS patients, however, the infection leads to encephalitis, which can persist in the long term. Patients infected with T. gondii who later contract AIDS may suffer a reactivation of the quiescent parasites confined to protective capsules, or cysts, in the brain. These patients may respond well to treatments that target the parasite and reduce swelling.

Life Cycle of Toxoplasma gondii

The life cycle of Toxoplasma gondii always involves cats that are infected by consuming infected animals. Humans and other incidental animal hosts are infected after consuming contaminated materials.
Toxoplasma gondii (light microscope, 400x) is a parasitic protozoan that causes toxoplasmosis. In AIDS patients, this infection can lead to encephalitis.
Credit: CDC/Dr. Morris T. Suggs, Jr.

African Sleeping Sickness

African sleeping sickness, a disease caused by parasites in genus Trypanosoma, is fatal, and treatments for it may also be fatal.
African sleeping sickness, also called trypanosomiasis, is a disease caused by members of the parasitic protozoa genus Trypanosoma. It originated in equatorial Africa, hence the name. There are two forms of this disease caused by two different subspecies of Trypanosoma brucei. The East African form occurs primarily in animals but is capable of infecting humans. If untreated, the East African form progresses quickly in humans and usually results in death within months of infection. The West African form occurs primarily in humans and if untreated progresses more slowly, usually resulting in death three to seven years after infection. Most cases of African sleeping sickness result from the West African form. The parasite is transmitted to humans via the bite of the tsetse fly. The parasites affect first the circulatory system, then the lymphatic system, and finally the central nervous system.

Life Cycle of Trypanosoma brucei

The life cycle of Trypanosoma brucei alternates between tsetse fly and mammalian, including human, hosts. The parasite multiplies in both types of host.
In the early stages of infection, while the parasites are in the circulatory and lymphatic systems, infected individuals experience intermittent fever, shortness of breath, blurred vision, weakness, chest pain, and anemia (low iron in the blood). Once the infection reaches the nervous system, patients experience headache, tremors, and lack of coordination. In the final stages of infection, paralysis occurs, and the individual falls into a coma, which is followed by death. The timing of the progression of symptoms varies from months to years, depending on which species of Trypanosoma infects the individual.

Treatment for African sleeping sickness involves the use of various selective toxins to kill the parasites. These toxins produce unpleasant and sometimes long-lasting side effects for the patient. Historically, arsenic has been used to fight the infection, but this can result in loss of vision. Today, pentamidine, suramin, melarsoprol, erflornithine, and nifurtimox are used, each of which is more toxic than the last. Melarsoprol can be quite effective at killing the parasites but may also kill the patient as well.

Very little can be done to prevent infection. A large number of species can host the parasites, and many varieties of tsetse fly can spread the pathogen. Furthermore, once in the bloodstream, the pathogen develops a unique glycoprotein each time the host's fever spikes, thus evading any antibodies the host has developed to the parasite. For this reason, development of a vaccine seems an unlikely prospect.
Trypanosoma brucei, a parasitic protozoan, is known to cause African trypanosomiasis, or sleeping sickness, which can be fatal.
Credit: CDC/Dr. Myron G. Schultz
Chagas disease is a disease caused by Trypanosoma cruzi, a parasitic protozoan similar to the T. brucei parasite that causes African sleeping sickness. It is transmitted by various reduviid bugs, also called assassin bugs. The disease is characterized by tissue inflammation—first at the site of the bite and then at various locations throughout the body as parasites make their way to lymph nodes and divide to form pseudocysts. Patients may suffer anemia, muscle pain, and nerve disorders, but symptoms may be very mild. In rare cases, death can occur, but most patients recover on their own. No treatment is currently available.
Trypanosoma cruzi (light microscope, 1,000x) is a parasitic protozoan transmitted by various reduviid bugs, such as the "kissing beetle," named for its habit of feeding on its victim's softer tissues, such as the mouth.
Credit: Curtis-Robles et al. (left), CDC/Dr. Mae Melvin (right)License: CC BY 4.0 (left)