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Abstract
Nocardiosis is an infectious disease caused by the gram-positive bacterium Nocardia spp. Although it is commonly accepted that exposure to Nocardia is almost universal, only a small fraction of exposed individuals develop the disease, while the vast majority remain healthy. Nocardiosis has been described as an “opportunistic” disease of immunocompromised patients, suggesting that exposure to the pathogen is necessary, but a host predisposition is also required. Interestingly, increasing numbers of nocardiosis cases in individuals without any detected risk factors, i.e., without overt immunodeficiency, are being reported. Furthermore, a growing body of evidence have shown that selective susceptibility to a specific pathogen can be caused by a primary immunodeficiency (PID). This raises the question of whether an undiagnosed PID may cause nocardiosis affecting otherwise healthy individuals. This review summarizes the specific clinical and microbiological characteristics of patients with isolated nocardiosis published during the past 30 years. Furthermore, it gives an overview of the known human immune mechanisms to fend off Nocardia spp. obtained from the study of PIDs and patients under immunomodulatory therapies.
Highlights
In 1888, while investigating a disease in cattle called “francine du boeuf,” the veterinarian Edmond Nocard identified a gram-positive, acid-fast agent as causative of this disease [1]
Even after appropriate treatment, mortality, and morbidity are high. Sometimes this is due to the late diagnosis and late application of the treatment given that this disease is not considered in the differential diagnosis in patients without risk factors
During the past two decades, the notion that severe infectious disease in patients otherwise healthy can arise from single-gene inborn errors of immunity has taken steam [27, 28]
Summary
In 1888, while investigating a disease in cattle called “francine du boeuf,” the veterinarian Edmond Nocard identified a gram-positive, acid-fast agent as causative of this disease [1]. After the generalization of antibiotic therapy, recovery rates improved to 54%, and an increased number of patients were every year [6] At this point, reports started to associate nocardiosis with underlying conditions. Reports started to be published describing severe nocardiosis in patients with primary immunodeficiencies (PID) such as hypogammaglobulinemia [13, 14], or chronic granulomatous disease (CGD) [15,16,17] (Table 2) At this point, nocardiosis was proposed to be an opportunistic infection [19,20,21]. The description of patients with isolated nocardiosis after the HIV outbreak has been increasing steadily since the mid80s, as evidenced by the number of case reports published in the literature over the last 30 years (Figure 1A). This observation indicates that the leading risk factor in developing nocardiosis is the immune status of the host rather than the virulence of the different Nocardia strains
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