Increased ShTAL1 IgE responses post-Praziquantel treatment may be associated with a reduced risk to re-infection in a Ghanaian S. haematobium-endemic community

Abstract

Background Evidence from recent studies in Schistosoma mansoni-endemic areas show an age-associated immunity that is positively correlated with IgE titres to Schistosoma mansoni-specific tegumental allergen-like protein 1 (SmTAL1). The structural homology between SmTAL1 and the S. haematobium-specific TAL1 (ShTAL1) has been verified, yet it remains unclear whether similar age- and immune-associated trends characterize ShTAL1. This community-based intervention study was conducted to assess whether ShTAL1IgE responses post-treatment with praziquantel (PZQ) might be associated with a reduced risk to re-infection with S. haematobium. Methodology/Principal findings This study was conducted at Agona Abodom, Central Region, Ghana, and involved 114 participants aged 6 to 55 years. EDTA blood samples were collected at baseline and 7 weeks after PZQ treatment (Follow-up). Baseline and Follow-up titres of specific IgG1, IgG4, and IgE antibodies to the S. haematobium-specific adult worm antigen (ShAWA), the Sh-specific soluble egg antigen (ShSEA), and the Sh-specific tegumental-allergen-like 1 protein (ShTAL1) in plasma samples were measured using sandwich ELISA. Participants at both time points also provided stool and urine for helminth egg detection by microscopy. Prevalence of S. haematobium at baseline was 22.80%, and decreased to 3.50% at Follow-up. The egg reduction rate (ERR) was 99.87%. Overall plasma levels of ShTAL1-IgE increased 7 weeks post-PZQ treatment, and with increasing age; whiles S. haematobium infection prevalence and intensity decreased. For S. haematobium-infected participants who were egg-negative at Follow-up (N = 23), minimal median levels of ShTAL1-IgE were observed for all age groups prior to treatment, whilst median levels increased considerably among participants aged 12 years and older at Follow-up; and remained minimal among participants aged 11 years or less. In the univariate analysis, being aged 12 years or older implied an increased likelihood for ShTAL1-IgE positivity [12–14 years (cOR = 9.64, 95% CI = 2.09–44.51; p = 0.004); 15+ years (cOR = 14.26, 95% CI = 3.10–65.51; p = 0.001)], and this remained significant after adjusting for confounders [12–14 years (aOR = 22.34, 95% CI = 2.77–180.14; p = 0.004); ≥15 years (aOR = 51.82, 95% CI = 6.44–417.17; p < 0.001)]. Conversely, median ShTAL1-IgG4 titres were hardly detectible at Follow-up. Conclusions/Significance These findings demonstrate that increased IgE levels to ShTAL1 7 weeks after PZQ treatment could be associated with a reduced risk to re-infection, and adds to the large body of evidence suggesting a protective role of the treatment-induced ShTAL1 antigen in schistosomiasis infections. It was also quite clear from this work that apart from being persistently S. haematobium-positive, elevated ShTAL1-IgG4 levels at Follow-up could be indicative of susceptibility to re-infection. These outcomes have important implications in vaccine development, and in shifting the paradigm in mass chemotherapy programmes from a ‘one-size-fits-all’ approach to more sub-group-/participant-specific strategies in endemic areas.

Review of Recent Prevalence of Urogenital Schistosomiasis in Sub-Saharan Africa and Diagnostic Challenges in the Field Setting

“…Every year, hundreds of articles are published on schistosomiasis. Table 2 summarizes the recently reported prevalence of UGS in SSA that was indexed in PubMed [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ,…”

“…As shown in Table 2 , most surveys screened SAC following WHO recommendations, which is a cost-effective approach and well reflects endemicity in the surveyed locality [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ,…”

Protective human IgE responses are promoted by comparable life-cycle dependent Tegument Allergen-Like expression in Schistosoma haematobium and Schistosoma mansoni infection

“…haematobium , although there is evidence for similar TAL1-specific IgE responses to those observed for S . mansoni [ 11 , 28 ]. Therefore, following publication of the S .…”

“…To date, only one member of the S. haematobium TAL protein family has been identified, a TAL1 orthologue which has a closely related sequence to the corresponding S. mansoni protein [11]. Furthermore, the relationship between TAL-specific antibodies and the acquisition of protective immunity is yet to be defined in S. haematobium, although there is evidence for similar TAL1-specific IgE responses to those observed for S. mansoni [11,28]. Therefore, following publication of the S. haematobium genome and the subsequent updated version [27], we take the opportunity to characterize the S. haematobium TAL proteins, specifically those proteins orthologous to the S. mansoni proteins associated with protective IgE responses: ShTAL1, ShTAL3, and ShTAL5.…”

Protective human IgE responses are promoted by comparable life-cycle dependent Tegument Allergen-Like protein expression inSchistosoma haematobiumandSchistosoma mansoniinfection

“…To date, only one member of the S. haematobium TAL protein family has been identified, a TAL1 orthologue which has a closely related sequence to the corresponding S. mansoni (9). Furthermore, the relationship between TAL-specific antibodies and the acquisition of protective immunity is yet to be defined in S. haematobium , although there is evidence for similar TAL1-specific IgE responses to those observed for S. mansoni (9, 27). Therefore, following publication of the S. haematobium genome and the subsequent updated version (28), we take the opportunity to characterize the S. haematobium TAL proteins, specifically those proteins orthologous to the S. mansoni proteins associated with protective IgE responses: ShTAL1, ShTAL3, and ShTAL5.…”