**6. Hyperinfection syndrome**

Since 1966, studies have reported that autoinfection may result in the dissemination of worms; denoted hyperinfection syndrome, the number of worms increases significantly, and worms are detectable in extraintestinal regions, with a mortality rate above 80% (Siddiqui & Berk, 2001). High-risk factors for hyperinfection and dissemination include corticosteroid therapy, malignancies, transplantation, malnutrition, hypogammaglobulinemia, and viral infections such as HIV (Human Immunodeficiency Virus) and HTLV-1 (Human T-Lymphotropic Virus Type 1) (Concha et al., 2005).

#### **6.1 Corticosteroids**

In recent decades, hyperinfection syndrome has increased significantly with the use of immunosuppressive drug therapy. Corticosteroids are widely prescribed drugs with potent immunosuppressive effects and are a major risk factor for the transformation of chronic strongyloidiasis into hyperinfection, which has a higher index of mortality (Armignacco et al., 1989; Al Maslamani et al., 2009). Corticosteroids are involved in the treatment of several diseases that are considered immunological abnormalities, such as lymphoma, rheumatoid arthritis, leprosy, chronic obstructive pulmonary disease (COPD), and polymyositis, leading to fatal hyperinfection in many cases (Keiser & Nutman, 2004).

However, the role of corticosteroids in susceptibility to severe *S. stercoralis* infection is poorly understood. One hypothesis is that both endogenous and exogenous corticosteroids promote immunosuppression by decreasing the number of inflammatory cells, such as eosinophils and mast cells, and suppressing the transcription of several cytokines. In addition, corticosteroids increase the apoptosis of Th2 lymphocytes (Genta, 1989). Corticosteroids may also have a direct effect on female worms by increasing the production of ecdysteroid-like molecules, hormones that control moulting in insects and possibly helminths (Genta, 1992). An increase in these molecules increases the moulting rate and transforms rhabditiform larvae into filariform larvae, increasing the worm burden and promoting hyperinfection and dissemination (Genta, 1992; Siddiqui et al., 2000).

#### **6.2 Hematologic and others malignancies**

Patients with hematologic malignancies have a high prevalence of *S. stercoralis* infection when compared with the global index. The reported cases of hematologic malignancies and *S. stercoralis* hyperinfection syndrome are associated with glucocorticoid treatment. The malignancy usually associated with *S. stercoralis* is lymphoma that is being treated with chemotherapy. Moreover, lung cancer has been associated with hyperinfection during the administration of immunosuppressive chemotherapy (Keiser & Nutman, 2004).

#### **6.3 Transplantation**

Hyperinfection syndrome is associated with transplants, and the progression of chronic intestinal infection before transplantation appears to be the most common mechanism. Hyperinfection cases following organ transplant principally occur during the initial months after transplantation, but the infection was acquired before transplantation in the majority of cases (Roxby et al., 2009). Higher mortality rates occur from extraintestinal strongyloidiasis, which in most of these cases are related to corticosteroid therapy to treat rejection (Keiser & Nutman, 2004).

Renal transplants are most commonly associated with hyperinfection, which is related to immunosuppressive treatments (Devault et al., 1990; Rajapurkar et al., 2007; Valar et al., 2007). Cases of hyperinfection have been described in transplant recipients of other organs, such as the liver (Vilela et al., 2008; Rodrigues-Hernandez et al., 2009), heart (Schaeffer et al., 2004), pancreas (Ben-Yousseff et al., 2005), lung (Balagopal et al., 2009), and intestine (Patel et al., 2008). Hyperinfection in hematopoietic stem cell transplant patients may be due to immunosuppressive therapies (Dulley et al., 2008; Wirk & Wingard, 2008).
