Strongyloides stercoralis infects 30 million people in 70 countries. Infection usually results in asymptomatic chronic disease of the gut, which can remain undetected for decades. However, in patients receiving long-term corticosteroid therapy, hyperinfection can occur, resulting in high mortality rates (up to 87%). Strongyloidiasis is difficult to diagnose because the parasite load is low and the larval output is irregular. Results of a single stool examination by use of conventional techniques fail to detect larvae in up to 70% of cases. Several immunodiagnostic assays have been found ineffective in detecting disseminated infections and show extensive cross-reactivity with hookworms, filariae, and schistosomes. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. This review describes the clinical manifestations of strongyloidiasis, as well as various diagnostic tests and treatment strategies.

Faecal smears of patients and Strongyloides stercoralis obtained from dogs were acid-fast stained with Kinyoun and Auramine O staining procedures. Both larval (rhabditiform and filariform) and adult parasites were effectively stained by these methods. Acid-fast staining can serve as a useful procedure for diagnosing strongyloidiasis.

Schistosomiasis is an important parasitic disease for which there is no available vaccine. We have focused on a functionally important antigen of Schistosoma mansoni, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective potential and antifecundity effect observed in murine models; and for its pivotal role in the immune evasion process. In the present study we report that a Sm-p80-based DNA vaccine formulation confers 38% reduction in worm burden in a nonhuman primate model, the baboon (Papio anubis). Animals immunized with Sm-p80-pcDNA3 exhibited a decrease in egg production by 32%. Sm-p80 DNA elicited specific immune responses that include IgG; its subtypes IgG1 and IgG2; and IgM in vaccinated animals. Peripheral blood mononuclear cells (PMBCs) from immunized animals when stimulated in vitro with Sm-p80 produced appreciably more Th1 response enhancing cytokines (IL-2, IFN-γ) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced appreciably more spot forming units for INF-γ than for IL-4 in enzyme-linked immunosorbent spot (ELISPOT) assays. Overall it appears that even though a mixed (Th1/Th2) type of humoral antibody response was generated following immunization with Sm-p80; the dominant protective immune response is Th1 type. These data reinforce the potential of Sm-p80 as an excellent vaccine candidate for schistosomiasis.

Advent of an effective schistosome vaccine would contribute significantly toward reducing the disease spectrum and transmission of schistosomiasis. We have targeted a functionally important antigen, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective and antifecundity potentials, and important role in the immune evasion process. In this study, we report that using two vaccination approaches (prime boost and recombinant protein), Sm-p80-based vaccine formulation(s) confer up to 70% reduction in worm burden in mice. Animals immunized with the vaccine exhibited a decrease in egg production by up to 75%. The vaccine elicited strong immune responses that included IgM, IgA, and IgG (IgG1, IgG2a, IgG2b, and IgG3) in vaccinated animals. Splenocytes proliferated in response to Sm-p80 produced Th1 and Th17 response enhancing cytokines. These results again emphasize the potential of Sm-p80 as a viable vaccine candidate for schistosomiasis.

SUMMARY Although there is an effective drug (praziquantel) available for the treatment of schistosomiasis, yet the disease is still spreading unabated and is rampant in 76 countries. Control via praziquantel treatment has so far been insufficient in reducing the disease transmission. Therefore a vaccine in addition to other strategies, for example, improving sanitation and introduction of new drugs are essential to successfully control and eventually eradicate schistosomiasis. To this effect we have targeted a functionally important antigen, Sm-p80 as a vaccine candidate. In the present study, full length cDNA of Sm-p80 was cloned in VR1020, a FDA approved vector for human use. The protective efficacy of this vaccine formulation was tested in a murine model. Sm-p80-VR1020 vaccine formulation was able to induce 47% reduction in worm burden. Serology on samples obtained from vaccinated animals revealed a strong antibody response which included IgG and all of its subtypes, IgM and IgA. Proliferating splenocytes in response to recombinant Sm-p80 produced a wide spectrum of cytokines representing Th1, Th2 and Th17 types, as ascertained via RT-PCR analysis. These findings further strengthen the importance of Sm-p80 molecule as a vaccine candidate for intestinal schistosomiasis.

The prophylactic efficacy of a schistosome antigen (Sm-p80) was tested in a nonhuman primate model, the baboon. Using a total of 28 baboons, different vaccination strategies were used including recombinant Sm-p80 protein formulated in Toll-like receptor 7 and Toll-like receptor 9 agonists, and DNA priming followed by boosting with protein plus adjuvants. Recombinant protein approaches provided levels of prophylactic efficacy of 52%-58%, whereas prime-boost approaches conferred 38%-47% protection in baboons. An appropriately balanced pro-inflammatory (T-helper 17 [Th17] and Th1) and anti-inflammatory (Th2) type of response was generated; the Th1 and Th17 types of immune responses appear to be indicative of increased prophylactic efficacy. Production and expression of several cytokines (interleukin 2 [IL-2], interferon γ, IL-12α, IL-1β, IL-6, and IL-22) were up-regulated in vaccinated animals. Human correlate studies revealed Sm-p80 reactivity with immunoglobulin G in human serum samples from schistosome-infected individuals. In addition, a complete lack of prevailing Sm-p80-specific immunoglobulin E in a high-risk or infected population was observed, thus minimizing the risk of hypersensitivity reaction following vaccination with Sm-p80 in humans. This study provided the proof of concept to move Sm-p80 forward into further preclinical development leading to human clinical trials.

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Summary Schistosomiasis is a neglected tropical disease (NTD) of public health importance. Despite decades of implementation of mass praziquantel therapy programs and other control measures, schistosomiasis has not been contained and continues to spread to new geographic areas. A schistosomiasis vaccine could play an important role as part of a multifaceted control approach. With regards to vaccine development, many biological bottlenecks still exist: the lack of reliable surrogates of protection in humans; immune interactions in co-infections with other diseases in endemic areas; the potential risk of IgE responses to antigens in endemic populations; and paucity of appropriate vaccine efficacy studies in nonhuman primate models. Research is also needed on the role of modern adjuvants targeting specific parts of the innate immune system to tailor a potent and protective immune response for lead schistosome vaccine candidates with the long-term aim to achieve curative worm reduction. This review summarizes the current status of schistosomiasis vaccine development.