Flying Fox Hemolytic Fever

By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: A novel mycoplasma causes a systemic infection characterized by fever, hemolytic anemia, and other cytopenias, sometimes with hemophagocytic lymphohistiocytosis, painful splenomegaly with risk of rupture, and response to doxycycline.

SOURCE: Descloux E, Mediannikov O, Gourinat AC, et al. Flying fox haemolytic fever, description of a new zoonosis caused by “Candidatus Mycoplasma haemohominis.” Clin Infect Dis 2020 Oct 29:ciaa1648. doi: 10.1093/cid/ciaa1648. [Online ahead of print.]

Descloux and colleagues previously detected DNA of a novel hemotropic mycoplasma they called Candidatus Mycoplasma haemohominis in the blood of a patient in New Caledonia with fever, hemolytic anemia, and hemophagocytosis in 2017. They have since tested, both retrospectively and prospectively, a series of patients in New Caledonia with similar clinical pictures for the presence of this organism and identified a total of 15 cases. Those selected for study had fever, splenomegaly, and hemolytic anemia with or without evidence of hemophagocytosis.

The median age of the 15 patients, all of whom were previously healthy, identified was 48 years (range, 36-72 years), and 11 were male. The incubation period ranged from three weeks to three months. All patients had splenomegaly (often painful) and persistent fever, and 80% had experienced weight loss.

Three patients, two of whom died, had splenic rupture. Fourteen had autoimmune hemolytic anemia, 13 had thrombocytopenia, 10 were leukopenic, and 13 had evidence of hemophagocytic lymphohistiocytosis (HLH). Candidatus Mycoplasma haemohominis DNA was detected in the blood of all 15 patients and was recovered in culture from one.

Thirteen of the patients had a history of contact with the blood of flying foxes in the process of hunting and/or cooking, and 13 also regularly ate them. DNA of the organism was detected in the blood of 16 (40%) of 40 flying foxes (genus Pteropus) as well as in nine of nine of hemophagoous “bat flies.”

Ten patients were treated with doxycycline for at least three weeks, and all had favorable outcomes. Treatment of three patients with a macrolide or ofloxacin was not successful. However, one patient treated with piperacillin-tazobactam and amikacin recovered. Four (27%) patients died.

COMMENTARY

Hemotropic mycoplasmas are known to cause infections, mostly asymptomatic, in a broad range of vertebrate animals, including bats, but some cause species-specific hemolytic anemia. In addition, scattered cases have been reported in humans from a number of countries, including in Europe, Asia, North and South America, and Africa. These cases, caused by various species, were associated with underlying immunocompromise and/or exposure to farm animals and suggest that although previously healthy individuals who become infected develop pauci-symptomatic bacteremia, those who have underlying immunocompromise experience hemolytic anemia.

Descloux et al provide strong evidence of a serious clinical illness in previously healthy individuals with a characteristic pattern caused by a novel hemotropic mycoplasma, Candidatus Mycoplasma haemohominis. After an incubation period of weeks to months, usually after exposure to the frugiferous bats commonly called flying foxes, patients develop persistent but fluctuating fever, splenomegaly that may be painful, autoimmune hemolytic anemia often with other cytopenias, and, in some cases, HLH.

Among the unusual features of the illness was the occurrence of splenic rupture in three patients. Patients responded to therapy with doxycycline.

Although this case series originated in the South Pacific islands of New Caledonia, the reports of human infections caused by other hemotropic mycoplasma on a number of continents makes it likely that cases will be encountered elsewhere, but the diagnosis will require effective molecular methods.