**5. Clinical manifestation**

The clinical presentation of strongyloidiasis varies with the status of the host´s immune system, and the infection is classified as acute, chronic or severe. Acute infections of strongyloidiasis manifest as a wide spectrum of clinical features ranging from asymptomatic disease to cutaneous (larva currens and urticaria), pulmonary (cough and tracheal irritation), and gastrointestinal symptoms (diarrhoea and constipation), although the majority of *S. stercoralis* infections are resolved (Mahmoud, 1996).

The ability of *S. stercoralis* to establish a cycle of autoinfection within the host results in chronic infections that can persist in an individual for decades. Chronic infections are often asymptomatic, but when symptoms occur they are usually mild, episodic and prolonged, including nausea, vomiting, diarrhoea, constipation, weight loss or cutaneous reactions (Grove, 1989).

Uncontrolled autoinfection of *S. stercoralis* is more likely to occur in immunosuppressed patients, leading to hyperinfection syndrome. The pulmonary phase of hyperinfection due to migrating larvae resembles Löffler syndrome with coughing and wheezing, asthma-like symptoms, haemorrhaging and pneumonia. In the intestine, symptoms include diarrhoea, nausea, vomiting, abdominal pain, and weight loss (Concha et al., 2005; Viney & Lok, 2007). Bacteremia is a common complication of hyperinfection syndrome and is caused by filariform larvae that may lead bacteria from the bowel to the bloodstream with subsequent secretion into the host circulation (Bamias et al., 2010). Pathogens such as *Streptococcus bovis, Escherichia coli, Klebsiella pneumonia* or *Enterobacter cloacae* are found during fatal complications of strongyloidiasis (Link & Orenstein, 1999). The mortality rate of dissemination associated with bacterial infections can reach approximately 90% (Igra-Siegman et al., 1981).

Dissemination occurs upon larval migration to organs beyond the range of the pulmonary phase, such as the liver, heart, lymph nodes, gallbladder, kidneys, pancreas, and brain (Keiser & Nutman, 2004). Petechiae and purpura have also been reported in disseminated cases as a result of larval migration through vessel walls, which promotes haemorrhage (Basile et al., 2010). Others complications of disseminated strongyloidiasis can occur and include syndromes such as cholecystitis, pancreatitis, paralytic ileus, intestinal perforation

Hyperinfection Syndrome in Strongyloidiasis 381

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 &

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

An important cause of immunodeficiency that is related to hyperinfection is malnutrition, particularly in developing countries. Malnutrition promotes disruption of the intestinal mucosa, impairing the host's ability to expel the parasite from the gut (Olsen et al., 2009).

Patients with immunodeficient conditions, such as hypogammaglobulinemia, may develop fatal hyperinfection. Case reports show that hypogammaglobulinemia is refractory to

Although HIV infection predisposes a patient to hyperinfection due to immunosuppression, few cases of *S. stercoralis* and AIDS have been described (Marcos et al., 2008). The association between *S. stercoralis* and HIV principally occurs in endemic areas (Siddiqui & Berk, 2001). The hyperinfection syndrome can occur in patient with HIV with immune reconstruction syndromes increased after starting of highly active antiretroviral therapy (Brown et al., 2006). On the other hand, the infection with *Strongyloides* may contribute to serious nutritional deciencies in HIV-infected individuals, such as anorexia and malabsorption (Lindo et al., 1998). However, the immunobiological and immunoregulatory mechanisms

HTLV-1 is a virus that infects T cells and induces lymphocyte proliferation with the production of a Th1-type immune response in humans. The genome of the HTLV-1virus is diploid and, following interaction with the immune system, HTLV-1 enables the transcription of the viral DNA by integrating into the host genome effectively evading immune surveillance without killing the host (Iriemenan et al., 2010). Strongyloidiasis is strongly associated with HTLV-1, which predisposes patients to severe infections by depressing cell-mediated immunity or IgE responses (Grove, 1996; Carvalho & Da Fonseca Porto, 2004). *Strongyloides* and HTLV-1 may promote the Th1-type response in patients, increasing interferon levels and decreasing Th2-type responses, such as interleukin 4 (IL-4), IL-5, IL-13, and IgE, important host defences against helminths, and a decrease in this response allows not only an increasing in autoinfection but also decreased parasite killing.

prolonged anthelmintic therapy (Brandt de Oliveira et al., 1981; Seet et al., 2005).

immunosuppressive therapies (Dulley et al., 2008; Wirk & Wingard, 2008).

Nutman, 2004).

**6.4 Malnutrition** 

**6.6 HIV** 

**6.7 HTLV-1** 

**6.5 Hypogammaglobulinemia** 

involving HIV and strongyloidiasis remain unclear.

or infarction, peritonitis, and sepsis (Krishnan et al., 2006). Although unusual, brain involvement can occur in disseminated infections, with symptoms including headache, focal seizures, altered mental state, secondary bacterial meningitis and coma (Dutcher et al., 1990).
