Research Article: A Public Health Response against Strongyloides stercoralis: Time to Look at Soil-Transmitted Helminthiasis in Full

Date Published: May 9, 2013

Publisher: Public Library of Science

Author(s): Alejandro J. Krolewiecki, Patrick Lammie, Julie Jacobson, Albis-Francesco Gabrielli, Bruno Levecke, Eugenia Socias, Luis M. Arias, Nicanor Sosa, David Abraham, Ruben Cimino, Adriana Echazú, Favio Crudo, Jozef Vercruysse, Marco Albonico, Peter Steinmann.

Abstract: Strongyloides stercoralis infections have a worldwide distribution with a global burden in terms of prevalence and morbidity that is largely ignored. A public health response against soil-transmitted helminth (STH) infections should broaden the strategy to include S. stercoralis and overcome the epidemiological, diagnostic, and therapeutic challenges that this parasite poses in comparison to Ascaris lumbricoides, Trichuris trichiura, and hookworms. The relatively poor sensitivity of single stool evaluations, which is further lowered when quantitative techniques aimed at detecting eggs are used, also complicates morbidity evaluations and adequate drug efficacy measurements, since S. stercoralis is eliminated in stools in a larval stage. Specific stool techniques for the detection of larvae of S. stercoralis, like Baermann’s and Koga’s agar plate, despite superiority over direct techniques are still suboptimal. New serologies using recombinant antigens and molecular-based techniques offer new hopes in those areas. The use of ivermectin rather than benzimidazoles for its treatment and the need to have curative regimens rather than lowering the parasite burden are also unique for S. stercoralis in comparison to the other STH due to its life cycle, which allows reproduction and amplification of the worm burden within the human host. The potential impact on STH of the benzimidazoles/ivermectin combinations, already used for control/elimination of lymphatic filariasis, should be further evaluated in public health settings. While waiting for more effective single-dose drug regimens and new sensitive diagnostics, the evidence and the tools already available warrant the planning of a common platform for STH and S. stercoralis control.

Partial Text: Soil transmitted helminthiasis (STH) affects up to one in four individuals in the world, disproportionately affecting impoverished populations without access to adequate water, sanitation, and opportunities for socioeconomic development [1]. Efforts to control the impact of STH are based on public health interventions that have periodic anthelminthic treatment, primarily of children, as the foundation for school or community based interventions. Attention has historically focused on just four species of STH, A. lumbricoides, T. trichiura, and hookworms (Ancylostoma duodenale and Necator americanus). Due to the challenge of measuring the disease burden and monitoring the control intervention, the role of S. stercoralis, which is as much an STH as the other four by its standard definition, has been neglected in the repertoire of strategies to reduce the burden of these neglected tropical diseases (NTDs) through public health interventions [2]. Main characteristics of STH and S. stercoralis infections are illustrated in Table 1.

Strongylodiasis is best known in the developed world for the severe consequences of the hyperinfection syndromes linked to immunosuppression caused by diseases like lymphomas, leukemias, or the use of corticosteroids [7]. This clinical entity, which in resource-poor countries is probably associated with widespread malnutrition, is probably just the tip of an iceberg of unknown size. Defining the denominator of patients infected by S. stercoralis and the assessment of associated morbidity including the proportion of those that suffer hyperinfection in a given community is essential to better identify risk factors, understand pathogenesis, and plan control measures in its natural setting.

Most of the difficulties posed in the measurement of S. stercoralis infections and its consequences rely on the challenging aspects of its diagnosis, which ultimately affect its incorporation into a control package with the other STH. In terms of diagnostics, Kato Katz (the diagnostic method recommended by WHO) and McMaster are techniques made to detect (and quantitate) eggs, which do not detect S. stercoralis larvae [13]. Even new developments in this area, like the FLOTAC, an improvement of the McMaster, focus on egg detection and fail to detect the presence of S. stercoralis, which is diagnosed in stool exams through the identification of its larval stages [14], [15]. At present the two most appropriate diagnostic tools for the diagnosis of S. stercoralis are the Baermann and the Harada Mori methods, although their sensitivity is not optimal; the agar plate method is more sensitive but also more expensive and laborious [3].

Current therapy is another issue to be revised if S. stercoralis is to be considered in the spectrum of targeted parasites amenable to public health control. Neither of the recommended drugs for use in large scale interventions to control STH infections, which include the benzimidazoles albendazole and mebendazole, levamisole, and pyrantel/oxantel have any significant activity against S. stercoralis, at least in single doses as recommended for preventive chemotherapy interventions [1], [20]. In terms of treatment goals, while lowering parasite burden in the group of individuals with moderate and high worm burdens is, from an arguable public health point of view, a reasonable goal for A. lumbricoides, T. trichiura, and hookworms [21], [22], this is not true for S. stercoralis. The peculiar life cycle of S. stercoralis, and specifically this worm’s unique (among STH) ability to reproduce within the human host, makes anything but parasitologic cure a treatment failure and therefore, any measure of parasite load reduction would not be a measure of success as for the other STH [23]. This last reason is what makes a drug like albendazole, with cure rates of approximately 40% when used in single-dose regimens, an unsatisfactory option for S. stercoralis[24], [25]. This difference in life cycles results in having at a maximum one adult worm per each invasive egg or larva that infects the host for A. lumbricoides, T. trichiura, and hookworms, but infinite numbers (resembling the situation in protozoan and bacterial infections) for S. stercoralis. Larvae from this parasite hatch in the stool, rapidly evolve into infective L3 filariform larvae, and re-infect the same individual, perpetuating the infection in healthy hosts and through the expansion of this re-infection step, overwhelm the host in the context of immune suppression [7]. In reference to immune protection, it is clear that acquired immunity develops in humans to infection with S. stercoralis, on the basis of the antibody responses that develop to the infection [26]. Furthermore, acquired protective immunity to the infection has been described extensively in animal models [27]. However, the lifelong nature of infections in humans argues that host immunity may limit worm burden, but it is not sufficient to eradicate it.

Epidemiologic studies looking into the distribution of S. stercoralis in communities have shown prevalence peaks in adolescents, remaining stable in adults, with a similar distribution as hookworms. Some studies have shown no gender difference and others have found it more prevalent in males, possibly representing differential exposure [9], [35], [36]. Findings of higher burden in the adult population challenge the current policies of focusing interventions (and also drug donations) in school-age and preschool-age children. WHO guidelines offer a clear stepwise approach to the community based treatment of STH through anthelminthic therapy, with the 20% and 50% thresholds of combined prevalence for any of the major STH triggering the use of preventive chemotherapy interventions once or twice a year, respectively [13]. While this strategy is in use around the world and delivering measurable benefits, there is room for further study of this strategy in order to provide scientific support to the expansion or modification of this approach. Among these unsolved areas is the definition of an appropriate prevalence threshold that should trigger community treatments for S. stercoralis, considering the particularities of the life cycle and treatment goals discussed above. The search for new diagnostic tools for S. stercoralis should not hamper the development of strategies for the implementation of control programs. The use of the available, albeit moderately sensitive, direct diagnostic tools in sentinel sites should allow predicting a good enough picture of the distribution of S. stercoralis that could justify a therapeutic intervention. More evidence and data are needed, however, to define such prevalence thresholds.