Is Human Immunodeficiency Virus Infection a Risk Factor for Strongyloides stercoralis Hyperinfection and Dissemination

Strongyloides stercoralis was first identified in post-mortem examination of the gastrointestinal tract of five French soldiers from Cochin, China, in 1876. Since then it has been recognized that infection with this organism can persist for decades. This is due to an autoinfective process whereby rhabditiform larvae that are excreted by the adult worm are converted to infectious filariform larvae in the large intestine where they can then reinfect the host. Under normal conditions this conversion in humans is quite limited, with most conversions occurring in the soil. Occasionally large numbers of rhabditiform larvae transform into infective filariform larvae in the human gastrointestinal tract, which results in a more severe form of the autoinfective cycle. This is referred to as hyperinfection syndrome and can result in dissemination of the larvae to other organs in the host with potentially fatal consequences. The hyperinfection syndrome has been linked to immunosuppression. In particular, conditions that impact on cell-mediated immunity have been more closely identified as risk factors for the development of this syndrome. The two conditions that have been most frequently recognized as predisposing factors for the development of the hyperinfection syndrome are corticosteroid use [1,2] and human Tlymphotropic virus type 1 (HTLV-1) infection [3]. Studies of disseminated disease in organ transplant patients, asthmatics, patients with chronic lung disease, and patients with autoimmune disease have shown that corticosteroid therapy has been a common denominator in the development of severe infection. When acquired immune deficiency syndrome (AIDS) was first described, it was predicted that there would be an outbreak of disseminated strongyloidiasis, especially in patients from the developing world, where S. stercoralis is endemic. Prior to the recognition of the human immunodeficiency virus (HIV), the diagnosis of AIDS was based on the presence of a selected group of opportunistic infections in patients who had no other identifiable predisposing condition. Disseminated strongyloidiasis was among this list of opportunistic infections. These initial concerns do not appear to have been warranted. In necropsy studies in HIVinfected patients in both Brazil and Africa, areas where the incidence of strongyloidiasis is high, there was not a single case of disseminated disease [4,5]. Although it is possible that cases might have gone unrecognized, since clinical monitoring in those parts of the world where strongyloidiasis is endemic might have been less comprehensive than in more developed areas, the relative paucity of cases led the CDC and the WHO to remove disseminated strongyloidiasis from its list of signature infections in 1987. Since then there have been only 40 cases of hyperinfection and disseminated strongyloidiasis in HIV-infected individuals reported in the medical literature. Most of these individuals had AIDS and many were also receiving corticosteroids. Of note, HIV infection does not protect individuals from acquiring intestinal strongyloidiasis. Several studies have documented increased rates of S. stercoralis infection among HIV-infected individuals. Assefa et al. found a 21-fold increased prevalence of S. stercoralis infection among HIV-positive compared to HIV-negative patients in southern Ethiopia [6]. Studies in Brazil have shown similar results [7]. However, this increased predilection for intestinal S. stercoralis infection among HIV-infected individuals does not seem to be predictive of an increased incidence of hyperinfection and dissemination. The predominant immunosuppressive effect of HIV infection is a cellular immune deficiency as evidenced by a progressive decline in CD4+ lymphocytes. However, within the CD4+ cell population, there is a relatively greater decline in the activity of the type 1 T helper (Th1) cells than the type 2 T helper (Th2) cells [8,9]. Th1 cells produce a variety of proinflammatory cytokines that modulate the cellular immune response including interferon gamma (IFN-c), interleukin 2 (IL-2), and tumor necrosis factor alpha (TNF-a) [10]. Th2 cells, on the other hand, are more active in mediating humoral immunity and produce cytokines IL-4, IL-5, IL10, and IL-13. The concept of a Th1 to Th2 cytokine shift in the course of HIV infection has been advanced by some investigators as a marker for HIV progression [10]. Others have not confirmed these findings and they remain somewhat controversial [11]. Nevertheless, whereas there is profound loss of Th1 immune activity in patients with advanced AIDS, there may be little change in Th2mediated cytokine activity. Indeed, levels of the Th2 cytokines IL-4 and IL-10 have been found to be higher in HIV-infected patients, both with and without opportunistic infections, than in uninfected controls [12]. The potential consequence of