Fatal Myositis Due to a Mosquito Pathogen

Abstract & Commentary

Synopsis: A Microsporidia species, never previously isolated from deep tissues of humans, was the cause of fatal myositis in a patient with diabetes and rheumatoid arthritis, who was being treated with infliximab.

Source: Coyle CM, et al. Fatal Myositis Due to the Microsporidian Brachiola algerae, a Mosquito Pathogen. N Engl J Med. 2004;351:42-47.

A 57-year old Pennsylvania woman with rheumatoid arthritis and diabetes presented with a 6-week history of fever, fatigue, and generalized muscle and joint pains. Six months earlier, she began receiving infliximab at intervals of 3 to 4 weeks. Within the prior year, she had also been treated with 15 mg of methotrexate per week and 20 mg of leflunomide (a pyrimidine synthesis inhibitor) per day. In addition, she had been on 3-10 mg of prednisone daily for several decades. The patient had had no recent travel and no known contact with animals.

Muscle biopsies of the patients left anterior thigh demonstrated microorganisms consistent with microsporidia. Genetic sequencing of the biopsy and tissue culture material confirmed that the organism was Brachiola algerae. Despite treatment with albendazole, clindamycin, metronidazole, atovaquone, and itraconazole, the patient continued to deteriorate, developing Pneumocystis jiroveci (formerly carinii) pneumonia, eventually dying of a massive cerebrovascular infarction. A postmortem muscle biopsy showed tissue necrosis and persistence of organisms.

Comment by Mary-Louise Scully, MD

Microsporidia are obligate intracellular eukaryotes that can infect almost all animal phyla, both vertebrates and invertebrates. Genera and species that have been reported to cause human disease include nosema (Nosema corneum, renamed Vittaforma corneae, and Nosema algerae, renamed Brachiola algerae), Pleistophora, Enterocytozoon, Encephalitozoon, Septata (reclassified as Encephalitozoon), Trachipleistophora, Brachiola, and Microsporidium.1 Enterocytozoon bieneusi is a microsporidia often associated with chronic diarrhea in patients with HIV infection, as well as among transplant patients.2

Although 3 other genera of microsporidia have been associated with myositis, this is the first case secondary to B. algerae, which had only previously been reported as a cause of superficial corneal ulceration in an immunocompetent patient.3 B. algerae is capable of infecting many mosquito genera throughout the world, including Culex, Anopheles, and Aedes, and has even been investigated as a potential pesticide. Mosquitoes infected with B. algerae have decreased life spans, both decreased reproductive capacity and susceptibility to malarial parasites. The organism grows best at 26° to 37°C, and in animal models, B. algerae needs to first establish infection in a cooler superficial body location (skin, ears, or nose) before causing disseminated disease. For example, athymic mice, when inoculated superficially, developed disseminated disease, but intravenous or oral inoculation did not establish infection.4 Although it is possible, the organism was transmitted to the patient as a result of a feeding mosquito. There are no published reports of B. algerae spores in the salivary glands of mosquitoes. Therefore, Coyle and colleagues conclude that that their patient more likely acquired the infection through crushing an infected mosquito while it was feeding, thereby inoculating B. algerae spores into the bite wound.

Infliximab, a monoclonal antibody that binds soluble and membrane bound tumor necrosis factor-a (TNF-a), is a highly effective drug for patients with rheumatoid arthritis. However, infliximab has also been associated with increased risk of infection with Mycobacterium tuberculosis, Histoplasma capsulatum, and Pneumocystis. This report of fatal B. algerae myositis is a reminder for physicians to remain vigilant for such infections in patients treated with infliximab.

References

1. Wittner M, et al. The Microsporidia and Microsporidiosis. Washington D.C.:ASM Press, 1999.

2. Rabodonirina M, et al. Enterocytozoon bieneusi as a Cause of Chronic Diarrhea in a Heart Lung Recipient Who Was Negative for Human Immunodeficiency Virus. Clin Inf Dis. 1996;23:114-117.

3. Visvesvara GS, et al. Isolation of Nosema algerae From the Cornea of an Immunocompetent Patient. J Eukaryot Microbiol. 1999;46:108.

4. Koudela B, et al. The Human Isolate of Brachiola algerae: Development in SCID Mice and Description of Its Fine Structure Features. Parasitology. 2001;123: 153-162.

Mary-Louise Scully, MD, Sansum-Santa Barbara Medical Foundation Clinic, Santa Barbara, Calif. is Associate Editor of Travel Medicine Advisor.