scholarly journals Immunoglobulin E (IgE) Responses to Paramyosin Predict Resistance to Reinfection with Schistosoma japonicum and Are Attenuated by IgG4

2009 ◽  
Vol 77 (5) ◽  
pp. 2051-2058 ◽  
Author(s):  
Mario Jiz ◽  
Jennifer F. Friedman ◽  
Tjalling Leenstra ◽  
Blanca Jarilla ◽  
Archie Pablo ◽  
...  

ABSTRACT Schistosomiasis remains a public health concern in developing countries, and rapid reinfection fostered by continued exposure to contaminated water sources necessitates a vaccine to augment current mass treatment-based control strategies. We report isotype-specific (immunoglobulin A [IgA], IgE, IgG1, IgG4, and IgG) antibody responses to soluble worm antigen preparation and the recombinant vaccine candidates rSj97, rSj67, and rSj22 from a Schistosoma japonicum-infected cohort in Leyte, the Philippines, where schistosomiasis is endemic. Sera were collected from infected individuals 1 month posttreatment with praziquantel, and antibody responses were measured using a bead-based multiplex platform. Reinfection was monitored by stool sampling every 3 months, and data up to 1 year were included in the analysis (n = 553). In repeated-measures models, individuals with detectible IgE responses to rSj97 had a 26% lower intensity of reinfection at 12 months posttreatment compared to nonresponders after adjusting for age, gender, village, exposure, pretreatment infection intensity, and clustering by household (P = 0.018). In contrast, IgG4 responses to rSj97 as well as rSj67 and rSj22 were associated with markedly increased reinfection intensity. When stratified by IgG4 and IgE responder status, individuals with IgE but not IgG4 responses to rSj97 (n = 16) had a 77% lower intensity of reinfection at 12 months compared to individuals with IgG4 responses but not IgE responses (n = 274), even after adjusting for potential confounders (P = 0.016). Together with our previously described protective cytokine responses, these data further support paramyosin as a leading vaccine candidate for human schistosomiasis japonica and underscore the importance of careful adjuvant selection to avoid the generation of blocking IgG4 antibody responses.

2021 ◽  
Vol 223 (7) ◽  
pp. 1265-1274
Author(s):  
Hannah W Wu ◽  
Sangshin Park ◽  
Sunthorn Pond-Tor ◽  
Ron Stuart ◽  
Sha Zhou ◽  
...  

Abstract Schistosomiasis remains a leading cause of chronic morbidity in endemic regions despite decades of widespread mass chemotherapy with praziquantel. Using our whole proteome differential screening approach, and plasma and epidemiologic data from a longitudinal cohort of individuals living in a Schistosoma japonicum–endemic region of the Philippines, we interrogated the parasite proteome to identify novel vaccine candidates for Schistosoma japonicum. We identified 16 parasite genes which encoded proteins that were recognized by immunoglobulin G or immunoglobulin E antibodies in the plasma of individuals who had developed resistance to reinfection, but were not recognized by antibodies in the plasma of individuals who remained susceptible to reinfection. Antibody levels to Sj6-8 and Sj4-1 measured in the entire cohort (N = 505) 1 month after praziquantel treatment were associated with significantly decreased risk of reinfection and lower intensity of reinfection over 18 months of follow-up.


2020 ◽  
Vol 6 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Jan Clyden B. Tenorio ◽  
Elizabeth C. Molina

Background and Aim: Schistosomiasis is one of the seven neglected tropical diseases that are of public health concern in the Philippines. The disease is prevalent in few of the barangays (communities) in Koronadal City, Philippines. Status of the Schistosoma japonicum infections in domestic animal reservoir host has yet to be explored in these endemic communities. The study aimed to determine the prevalence and infection intensity of the disease in cattle and water buffaloes of endemic communities of Koronadal City. Materials and Methods: Schistosomiasis was investigated in 70 cattle and 38 water buffaloes from three endemic communities in Koronadal City. The copro-parasitological technique used was the formalin-ethyl acetate sedimentation method. Results: S. japonicum infection was observed in 48.6% of cattle and 60.5% in water buffaloes. The bovine contamination index indicated that all infected animals released 3,505,500 eggs/day. On average, infected cattle released 1,674,500 eggs daily, while infected water buffaloes liberated 1,932,000 eggs in the environment daily. Conclusion: Cattle and water buffaloes in these endemic areas are infected with S. japonicum. These animals release large numbers of eggs in the environment daily; hence, played an important role in disease transmission. Those living and working in endemic areas should be aware of the inherent dangers of the disease.


2022 ◽  
pp. 1-20
Author(s):  
Soledad Natalia M. Dalisay ◽  
Vicente Y. Belizario ◽  
Joseph Aaron S. Joe ◽  
Carlo R. Lumangaya ◽  
Reginaldo D. Cruz

Abstract Schistosomiasis japonica remains a public health concern in many areas of the Philippines. Periodic Mass Drug Administration (MDA) to at-risk populations is the main strategy for morbidity control of schistosomiasis. Attaining MDA coverage targets is important for the reduction of morbidity and prevention of complications due to the disease, and towards achieving Universal Health Care. The study employed a qualitative case study design. Key informant interviews and focus group discussions were conducted to provide in-depth and situated descriptions of the contexts surrounding the implementation of MDA in two selected villages in known schistosomiasis-endemic provinces in Mindanao in the Philippines. Data analysis was done using the Critical Ecology for Medical Anthropology (CEMA) model coupled with the intersectionality approach. It was found that within various areas in the CEMA model, enabling as well as constraining factors have been encountered in MDA in the study settings. The interplay of income class, geographical location, gender norms and faith-based beliefs may have led to key populations being missed during the conduct of MDA in the study sites. The constraints faced by the target beneficiaries of MDA, as well as programme implementers, must be addressed to enhance service delivery and to control morbidity due to schistosomiasis. Improving compliance with MDA also requires a holistic, integrated approach to addressing barriers to participation, which are shaped by wider socio-political and power structures.


Parasitology ◽  
2019 ◽  
Vol 147 (8) ◽  
pp. 889-896 ◽  
Author(s):  
Yi Mu ◽  
Pengfei Cai ◽  
Remigio M. Olveda ◽  
Allen G. Ross ◽  
David U. Olveda ◽  
...  

AbstractNovel tools for early diagnosis and monitoring of schistosomiasis are urgently needed. This study aimed to validate parasite-derived miRNAs as potential novel biomarkers for the detection of human Schistosoma japonicum infection. A total of 21 miRNAs were initially validated by real-time-polymerase chain reaction (RT-PCR) using serum samples of S. japonicum-infected BALB/c mice. Of these, 6 miRNAs were further validated with a human cohort of individuals from a schistosomiasis-endemic area of the Philippines. RT-PCR analysis showed that two parasite-derived miRNAs (sja-miR-2b-5p and sja-miR-2c-5p) could detect infected individuals with low infection intensity with moderate sensitivity/specificity values of 66%/68% and 55%/80%, respectively. Analysis of the combined data for the two parasite miRNAs revealed a specificity of 77.4% and a sensitivity of 60.0% with an area under the curve (AUC) value of 0.6906 (P = 0.0069); however, a duplex RT-PCR targeting both sja-miR-2b-5p and sja-miR-2c-5p did not result in an increased diagnostic performance compared with the singleplex assays. Furthermore, the serum level of sja-miR-2c-5p correlated significantly with faecal egg counts, whereas the other five miRNAs did not. Targeting S. japonicum-derived miRNAs in serum resulted in a moderate diagnostic performance when applied to a low schistosome infection intensity setting.


PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0224617 ◽  
Author(s):  
Raffy Jay C. Fornillos ◽  
Marcello Otake Sato ◽  
Ian Kim B. Tabios ◽  
Megumi Sato ◽  
Lydia R. Leonardo ◽  
...  

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Pengfei Cai ◽  
Yi Mu ◽  
Kosala G. Weerakoon ◽  
Remigio M. Olveda ◽  
Allen G. Ross ◽  
...  

Abstract Background Zoonotic schistosomiasis, caused by Schistosoma japonicum, remains a major public health problem in the Philippines. This study aimed to evaluate the commercially available rapid diagnostic point-of-care circulating cathodic antigen (POC-CCA) test in detecting individuals infected with S. japonicum in a human cohort from an endemic area for schistosomiasis japonica in the Philippines. Methods Clinical samples were collectedin 18 barangays endemic for S. japonicum infection in Laoang and Palapag municipalities, Northern Samar, the Philippines, in 2015. The presence of CCA in filter-concentrated urine samples (n = 412) was evaluated using the commercial kits and the results were converted to images, which were further analyzed by ImageJ software to calculate R values. The diagnostic performance of the immunochromatographic POC-CCA test was compared using the Kato-Katz (KK) procedure, in-house enzyme-linked immunosorbent assays (ELISAs) and droplet digital (dd) PCR assays as reference. Results The POC-CCA test was able to detect S. japonicum-infected individuals in the cohort with an eggs per gram of faeces (EPG) more than or equal to 10 with sensitivity/specificity values of 63.3%/93.3%. However, the assay showed an inability to diagnose schistosomiasis japonica infections in all cohort KK-positive individuals, of which the majority had an extremely low egg burden (EPG: 1–9). The prevalence of S. japonicum infection in the total cohort determined by the POC-CCA test was 12.4%, only half of that determined by the KK method (26.2%). When compared with the ELISAs and ddPCR assays as a reference, the POC-CCA assay was further shown to be a test with low sensitivity. Nevertheless, the assay exhibited significant positive correlations with egg burden determined by the KK technique and the target gene copy number index values determined by the ddPCR assays within the entire cohort. Conclusions By using in silico image analysis, the POC-CCA cassette test could be converted to a quantitative assay to avoid reader-variability. Because of its low sensitivity, the commercially available POC-CCA assay had limited potential for determining the status of a S. japonicum infection in the target cohort. The assay should be applied with caution in populations where schistosome parasites (especially S. japonicum) are present at low infection intensity. Graphic abstract


2021 ◽  
Vol 7 (1) ◽  
pp. 12-18
Author(s):  
Rohani C. Navarro ◽  
Aleyla E. de Cadiz ◽  
Jordan M. Fronda ◽  
Lynnell Alexie D. Ong ◽  
Vicente Y. Belizario Jr.

Background and Aim: Schistosomiasis (SCH) japonica is a zoonotic disease that can infect several mammalian hosts. Bovines, particularly water buffaloes, are considered the most important reservoir hosts due to the high levels of schistosome eggs, they excrete into the environment. In the Philippines, the previous studies have revealed a high prevalence of SCH in bovines in selected provinces in Luzon, Visayas, and Mindanao. However, there is a lack of studies on SCH in the Davao Region, Mindanao, where the infection remains a public health concern. This study aimed to determine the prevalence of SCH in water buffaloes in four barangays (villages) each in Braulio Dujali, Davao del Norte and Maragusan, Davao de Oro, Southeastern Mindanao, the Philippines. Materials and Methods: Fecal samples from 91 water buffaloes were collected intrarectally, processed using the formalin-ethyl acetate sedimentation technique, and examined microscopically to determine the prevalence of SCH. Results: A total of three water buffaloes (8.6%) in Maragusan were determined to be positive for Schistosoma japonicum, while none in Braulio Dujali. The prevalence of other parasites (Fasciola spp. [53.8%], Paramphistome spp. [20.9%], Amphistome spp. [16.5%], Strongyle spp. [11.0%], Balantidium spp. [9.9%], Eurytrema spp. [2.2%], and Gongylonema pulchrum [1.1%]) was also observed. Conclusion: The results of the study provide baseline data on the presence of S. japonicum in water buffaloes in the Davao Region, Mindanao. Strategies for controlling and eliminating SCH in animal reservoir hosts, especially in water buffaloes, are necessary for the long-term control and elimination of SCH in humans.


2006 ◽  
Vol 74 (1) ◽  
pp. 370-381 ◽  
Author(s):  
Tjalling Leenstra ◽  
Luz P. Acosta ◽  
Hai-Wei Wu ◽  
Gretchen C. Langdon ◽  
Julie S. Solomon ◽  
...  

ABSTRACTAlthough schistosomiasis is effectively treated with Praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Using a longitudinal treatment-reinfection study design with 616 participants 7 to 30 years of age, we evaluated the relationship between cytokine responses toSchistosoma japonicumsoluble adult worm extract (SWAP), Sj97, Sj22.6, and Sj67, measured 4 weeks after treatment with Praziquantel, and resistance to reinfection in a population from Leyte, The Philippines, whereS. japonicumis endemic.S. japonicumtransmission was high: 54.8% and 91.1% were reinfected within 6 and 18 months, respectively. A Th2 bias in the following cytokine ratios, interleukin-4 (IL-4)/IL-12, IL-5/IL-12, IL-13/IL-12, IL-4/gamma-IFN (IFN-γ), IL-5/IFN-γ, and IL-13/IFN-γ, in response to SWAP predicted a 1.4- to 2.9-month longer time to reinfection (P< 0.05) and a 27 to 55% lower intensity of reinfection (P< 0.05). Similarly, a Th2 bias in response to Sj97 predicted a 1.6- to 2.2-month longer time to reinfection (P< 0.05) and a 30 to 41% lower intensity of reinfection (P< 0.05). Only a high IL-5/IL-10 ratio in response to Sj22.6 predicted a 3.0-month-longer time to reinfection (P= 0.03). Cytokine responses to Sj67 were not associated with protection. In a large population-based treatment-reinfection study we found that Th2 responses to SWAP and Sj97 consistently predicted resistance to reinfection. These findings underscore Th2-type immune responses as central in human resistance toS. japonicumand support Sj97 as a leading vaccine candidate for this parasite.


2010 ◽  
Vol 79 (3) ◽  
pp. 1254-1261 ◽  
Author(s):  
Jonathan D. Kurtis ◽  
Ashley Higashi ◽  
Hai-Wei Wu ◽  
Fusun Gundogan ◽  
Emily A. McDonald ◽  
...  

ABSTRACTSchistosomes infect ∼40 million women of childbearing age and result in the elaboration of proinflammatory cytokines that have been implicated in fetal growth restriction. In murine models and two observational studies in humans, schistosome infection during pregnancy was associated with reduced birth weight, although a recent treatment trial inSchistosoma mansonidid not detect this association. We conducted an observational study among 99 pregnant women living in an area ofSchistosoma japonicumendemicity in the Philippines. We enrolled women at 32 weeks gestation and measuredS. japonicumand geohelminth infection intensity. We collected maternal peripheral blood at 32 weeks gestation and placental and cord blood at delivery to assess inflammatory status. At delivery, we collected a placental-tissue sample and measured birth weight. In multivariate models adjusted for geohelminths, maternal schistosomiasis was associated with increased levels of inflammatory cytokines in maternal peripheral (tumor necrosis factor alpha [TNF-α] and interleukin 10 [IL-10]), placental (TNF-α, IL-6, TNF-α receptor II [RII], and IL-1β), and cord (IL-1β and TNF-α RII) blood, as well as acute subchorionitis and increased TNF-α production by syncytiotrophoblasts assessed by immunohistochemistry (allP< 0.05). After adjusting for confounders, placental IL-1β, and TNF-α production by syncytiotrophoblasts was independently associated with decreased birth weight (bothP< 0.05). Our data indicate that maternal schistosomiasis results in a proinflammatory signature that is detectable in maternal, placental, and fetal compartments, and a subset of these responses are associated with decreased birth weight. This potential mechanistic link between maternal schistosomiasis and poor birth outcomes will contribute to the debate regarding treatment of maternal schistosome infections.


2021 ◽  
Vol 15 (9) ◽  
pp. e0009796
Author(s):  
Mario Jiz ◽  
Claro Mingala ◽  
Zhi-Qiang Fu ◽  
Melika Adriatico ◽  
Ke Lu ◽  
...  

In the past decade, ecological surveys emphasized rats and dogs as the most significant animal reservoirs for Schistosoma japonicum (S.j) in the Philippines. However, recent studies demonstrated 51–91% prevalence of schistosomiasis among water buffalo using qPCR in the Sj endemic regions in the Philippines. In order to resolve the inconsistency of reported surveys regarding Sj endemicity among carabao, a domestic water buffalo that is the most important draught animal, we introduced 42 schistosome negative water buffalo to Macanip, Jaro municipality, Leyte, the Philippines, a subsistence rice-farming village that has been the focus of schistosomiasis japonica studies of our group for the past 20 years. We conducted perfusion to the remaining 34 buffalo that survived 10 months of nature exposure and Typhoon Haiyan. Thirty-three water buffalo were found to be positive with at least 1 pair of worms from the mesenteric vein. The infection rate is 97%, with the worm burden of 94 (95% confidence interval, 49–138 worms) worms. To our knowledge, this is the first report about S. japonicum worm burden in naturally infected water buffalo in the Philippines. The fact that with less than one-year of exposure, in this human schistosomiasis endemic area, only 1 out of 34 water buffalo was uninfected is striking. Urgent attention is needed for a cost-effective technique for monitoring Sj infection in animals and humans. Meanwhile, intervention implementation, including water buffalo treatment and vaccination, should be taken into consideration.


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