Cryptococcus deuterogattii VGIIa Infection Associated with Travel to the Pacific Northwest Outbreak Region in an Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibody-Positive Patient in the United States

Abstract

Mortality rates associated with C. gattii infections are estimated to be between 13% and 33%, depending on an individual’s predisposition, and C. gattii has caused at least 39 deaths in the PNW region. There have been four other international travel cases reported in patients from Europe and Asia with travel history to the PNW, but this report describes the first North American traveler who acquired C. deuterogattii infection presenting within the United States and the first case of a C. deuterogattii outbreak infection associated with anti-GM-CSF autoantibodies. Early and accurate diagnoses are important for disease prevention and treatment and for control of infectious diseases. Continual reporting of C. deuterogattii infections is necessary to raise awareness of the ongoing outbreak in the PNW and to alert travelers and physicians to the areas of endemicity with potential risks.

Anticytokine autoantibodies leading to infection: early recognition, diagnosis and treatment options

“…High titre anti-GM-CSF plasma antibodies were detected. Genomic analysis of the isolated strain showed that it originated from a Cryptococcus outbreak area in the Pacific Northwest, which the patient visited 3 years earlier [31 ▪ ]. These cases document the expanding clinical manifestations and geographical distribution of anti-GM-CSF associated C. gattii infection.…”

Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

“…Anti-Granulocyte-Macrophage Colony-Stimulating Factor (Anti-GM-CSF) is an anti-cytokine autoantibody that interferes with GM-CSF activity that has recently been implicated as a cryptococcosis risk factor among immunocompetent individuals and has been observed in both children and adults [ 95 , 170 , 171 ]. Anti-GM-CSF has specifically been associated with CM caused by members within the C. gattii species complex and not C. neoformans [ 6 , 172 ]. Detecting Anti-GM-CSF antibodies has the potential to be a novel means of identifying at-risk individuals to aid in therapeutic approach, healthcare planning and public health efforts [ 173 , 174 ].…”

Cryptococcal infection in haematologic malignancies and haematopoietic stem cell transplantation

“…Granulocyte macrophage colony‐stimulating factor (GM‐CSF) has been shown to have an effect in host defence against Cryptococcus 105,106 . Several studies have shown an association between the presence of anti‐GM‐CSF autoantibodies and development of cryptococcal disease in otherwise immunocompetent patients, suggesting a potential therapeutic role 107‐109 . However, its efficacy and safety in patients with haematologic malignancies and HSCT has not been investigated.…”