Zoonotic schistosomiasis in Asia, caused by Schistosoma japonicum, remains a major public health concern in China and the Philippines. The developing epidemiological and socio-economic picture of the ...disease in endemic areas necessitates the development of affordable and highly accurate field diagnostics as an important component in evaluating ongoing integrated control and elimination efforts.
Three diagnostic methods, namely Kato-Katz (KK) stool microscopy, ELISA and droplet digital (dd) PCR assays, were compared by detecting infection in a total of 412 participants from an area moderately endemic for schistosomiasis in the Philippines.
This comprehensive comparison further defined the diagnostic performance and features for each assay. Compared with the ddPCR assay analysing DNA from faeces (F_ddPCR), which exhibited the highest sensitivity, the SjSAP4 + Sj23-LHD-ELISA had the best accuracy (67.2%) among all five ELISA assays assessed. Schistosomiasis prevalence determined by the SjSAP4 + Sj23-LHD-ELISA and ddPCRs was similar and was at least 2.5 times higher than obtained with the KK method. However, the agreement between these assays was low. In terms of cost and logistical convenience, the SjSAP4 + Sj23-LHD-ELISA represents a cost-effective assay with considerable diagnostic merits. In contrast, although the ddPCR assays exhibited a high level of diagnostic performance, the high cost and the need for specialized equipment presents a major obstacle in their application in screening campaigns.
The SjSAP4 + Sj23-LHD-ELISA represents a cost-effective tool for the diagnosis of schistosomiasis that could prove an important component in the monitoring of integrated control measures as elimination draws closer, whereas the ddPCR assays, in addition to their high sensitivity and specificity, are capable of quantifying infection intensity. However, the high cost of ddPCR hinders its wider application in screening programs, although it could be a valuable reference in the development and improvement of other diagnostic assays.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A ddPCR assay is presented to diagnose schistosomiasis japonica using feces, urine, saliva, and blood. The capability of the test to use noninvasive samples, its high sensitivity, and capacity to ...quantify infection intensity have public health implications for schistosomiasis control.
Abstract
Background
Schistosomiasis japonica remains a major public health and socioeconomic concern in Southeast Asia. Sensitive and accurate diagnostics can play a pivotal role in achieving disease elimination goals.
Methods
We previously reported a novel droplet digital polymerase chain reaction (ddPCR) assay targeting the mitochondrial gene nad1 to diagnose schistosomiasis japonica. The tool identified both prepatent and patent infections using Schistosoma japonicum DNA isolated from serum, urine, salivary glands, and feces in a murine model. The assay was validated here using clinical samples collected from 412 subjects resident in an area moderately endemic for schistosomiasis in the Philippines.
Results
S. japonicum DNA present in human stool, serum, urine, and saliva was detected quantitatively with high sensitivity. The capability to diagnose cases of human schistosomiasis using noninvasively collected clinical samples, the higher level of sensitivity obtained compared with the microscopy-based Kato-Katz test, and the capacity to quantify infection intensity have important public health implications for schistosomiasis control and programs targeting other neglected tropical diseases.
Conclusions
This verified ddPCR method represents a valuable new tool for the diagnosis and surveillance of schistosomiasis, particularly in low-prevalence and low-intensity areas approaching elimination and in monitoring where disease emergence or re-emergence is a concern.
Background Schistosoma japonicum is one of three major species of blood flukes causing schistosomiasis, a disease, which continues to be a major public health issue in the Philippines. SjSAP4, a ...member of a multigene family of saposin-like proteins, is a recognized immunodiagnostic biomarker for schistosomiasis japonica. This study aimed to identify linear B-cell epitopes on SjSAP4 and to validate their potential as components of a multi-epitope assay for the serological diagnosis of schistosomiasis japonica. Methodology SjSAP4-derived peptides were expressed as GST-peptide-fused proteins and these were Western blot probed with human serum samples from S. japonicum Kato-Katz (KK)-positive individuals and uninfected controls. A core epitope was further identified by Western blotting through probing a series of truncated peptides with the schistosomiasis patient sera. The diagnostic performance of the core epitope-containing peptides and the full-length SjSAP4 was evaluated by enzyme-linked immunosorbent assay (ELISA) using a panel of sera collected from subjects resident in a schistosomiasis-endemic area of the Philippines. Main findings As a result of the peptide mapping, one peptide (P15) was found to be highly immunogenic in the KK-positive individuals. We subsequently showed that -S.sup.163 QCSLVGDIFVDKYLD.sup.178 - is a core B-cell epitope of P15. Subsequent ELISAs incorporating SjSAP4, SjSAP4-Peptide and SjSP-13V2-Peptide showed a sensitivity of 94.0%, 46.0% and 74.0%, respectively, and a specificity of 97.1%, 100% and 100%, respectively. Notably, complementary recognition of the B-cell epitopes (SjSAP4-Peptide and SjSP-13V2-Peptide) was observed in a subset of the KK-positive individuals. A dual epitope-ELISA (SjSAP4-Peptide + SjSP-13V2-Peptide-ELISA) showed a diagnostic sensitivity of 84.0% and a specificity of 100%. Conclusions/Significance In this study, -S.sup.163 QCSLVGDIFVDKYLD.sup.178 - was identified as a dominant linear B-cell epitope on SjSAP4. This peptide and the complementary recognition of other B-cell epitopes using sera from different KK-positive individuals can provide the basis of developing a multi-epitope assay for the serological diagnosis of schistosomiasis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
4.
A new global strategy for the elimination of schistosomiasis Ross, Allen G.P., M.D., Ph.D; Chau, Thao N., M.P.H; Inobaya, Marianette T., M.Sc ...
International journal of infectious diseases,
01/2017, Letnik:
54, Številka:
C
Journal Article
Recenzirano
Odprti dostop
Abstract Mass drug administration utilising a single oral dose of 40 mg/kg of praziquantel (PZQ) has been endorsed and advocated by the World Health Organisation (WHO) for the global control and ...elimination of schistosomiasis. However, this strategy is failing primarily because the drugs are not getting to the people who need them the most. The current global coverage is 20%, the drug compliance rate is less than 50%, and the drug efficacy is approximately 50%. Thus in reality, only about 5% of the reservoir human population is actually receiving intermittent chemotherapy. Despite claims that more of the drug will soon be made available the current strategy is inherently flawed and will not lead to disease elimination. We discuss the many practical issues related to this global strategy, and advocate for an integrated control strategy targeting the life cycle and the most at-risk. Moreover, we discuss how an integrated control package for schistosomiasis should fit within a larger integrated health package for rural and remote villages in the developing world. A holistic health system approach is required to achieve sustainable control and ultimately disease elimination.
Chronic infection with
or
results in hepatic fibrosis of the human host. The staging of fibrosis is crucial for prognosis and to determine the need for treatment of patients with schistosomiasis. ...This study aimed to determine whether there is a correlation between the levels of serum exosomal micro-ribonucleic acids (miRNAs) (exomiRs) and fibrosis progression in schistosomiasis. Reference gene (RG) validation was initially carried out for the analysis of serum exomiRs expression in staging liver fibrosis caused by schistosome infection. The expression levels of liver fibrosis-associated exomiRs in serum were determined in a murine schistosomiasis model and in a cohort of Filipino schistosomiasis japonica patients (
= 104) with different liver fibrosis grades. Of twelve RG candidates validated, miR-103a-3p and miR-425-5p were determined to be the most stable genes in the murine schistosomiasis model and subjects from the schistosomiasis-endemic area, respectively. The temporal expression profiles of nine fibrosis-associated serum exomiRs, as well as their correlations with the liver pathologies, were determined in C57BL/6 mice during
infection. The serum levels of three exomiRs (miR-92a-3p, miR-146a-5p and miR-532-5p) were able to distinguish subjects with fibrosis grades I-III from those with no fibrosis, but only the serum level of exosomal miR-146a-5p showed potential for distinguishing patients with mild (grades 0-I) versus severe fibrosis (grades II-III). The current data imply that serum exomiRs can be a supplementary tool for grading liver fibrosis in hepatosplenic schistosomiasis with moderate accuracy.
Background. In the Philippines, the current national control strategy for schistosomiasis is annual mass drug administration (MDA) with 40 mg/kg of praziquantel in all schistosomiasis-endemic ...villages with a prevalence ≥ 10%. Methods. A cross-sectional survey of schistosomiasis was conducted in 2012 on 18 221 individuals residing in 22 schistosomiasis-endemic villages in the province of Northern Samar. The prevalence of schistosomiasis, intensity of Schistosoma infection, and morbidity of disease were assessed. Results. Despite an active schistosomiasis-control program in Northern Samar for > 30 years, which included a MDA campaign in the last 5 years, the mean prevalence of schistosomiasis among 10 435 evaluated subjects was 27.1% (95% confidence interval CI, 26.3%-28.0%), and the geometric mean intensity of infection among 2832 evaluated subjects was 17.2 eggs per gram of feces (95% CI, 16.4-18.1). Ultrasonography revealed high levels of schistosomiasis-induced morbidity in the schistosomiasis-endemic communities. Left lobe liver enlargement (≥ 70 mm) was evident in 89.3% of subjects. Twenty-five percent of the study population had grade II/III liver parenchyma fibrosis, and 13.3% had splenomegaly (≥ 100 mm). Conclusions. MDA on its own was insufficient to control the prevalence of schistosomiasis, intensity of Schistosoma infection, or morbidity of the disease. Alternative control measures will be needed to complement the existing national MDA program.
Novel 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.
The seasonality of influenza and respiratory syncytial virus (RSV) is well known, and many analyses have been conducted in temperate countries; however, this is still not well understood in tropical ...countries. Previous studies suggest that climate factors are involved in the seasonality of these viruses. However, the extent of the effect of each climate variable is yet to be defined.
We investigated the pattern of seasonality and the effect of climate variables on influenza and RSV at three sites of different latitudes: the Eastern Visayas region and Baguio City in the Philippines, and Okinawa Prefecture in Japan. Wavelet analysis and the dynamic linear regression model were applied. Climate variables used in the analysis included mean temperature, relative and specific humidity, precipitation, and number of rainy days. The Akaike Information Criterion estimated in each model was used to test the improvement of fit in comparison with the baseline model.
At all three study sites, annual seasonal peaks were observed in influenza A and RSV; peaks were unclear for influenza B. Ranges of climate variables at the two Philippine sites were narrower and mean variables were significantly different among the three sites. Whereas all climate variables except the number of rainy days improved model fit to the local trend model, their contributions were modest. Mean temperature and specific humidity were positively associated with influenza and RSV at the Philippine sites and negatively associated with influenza A in Okinawa. Precipitation also improved model fit for influenza and RSV at both Philippine sites, except for the influenza A model in the Eastern Visayas.
Annual seasonal peaks were observed for influenza A and RSV but were less clear for influenza B at all three study sites. Including additional data from subsequent more years would help to ascertain these findings. Annual amplitude and variation in climate variables are more important than their absolute values for determining their effect on the seasonality of influenza and RSV.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Preventive chemotherapy with 40 mg/kg of praziquantel has been endorsed and advocated by WHO for the global control of schistosomiasis, yet the drug does not prevent reinfection. In this Viewpoint, ...we discuss issues related to this control strategy, which is now implemented in many countries where schistosomiasis is endemic.
We performed this study to longitudinally compare rates of stunting, wasting and underweight among low birthweight (LBW), non-LBW, and/or small-for-gestational age (SGA) and non-SGA infants in Leyte, ...The Philippines and factors that predicted catch up. Birthweights of 357 infants born in Leyte, The Philippines were obtained within 48 hours of delivery and infants were evaluated at one, six and 12 months. Newborns were classified as LBW, SGA, or both. We derived length-for-age, weight-for-length and weight-for-age Z-scores using WHOAnthro. Generalized estimating equations models were used to compare the differences in prevalence and mean Z-scores for these growth and nutritional outcomes, with separate models made with LBW and SGA as distinct primary predictors. We compared the longitudinal risk of stunting, wasting and underweight during infancy among LBW versus non-LBW and SGA versus non-SGA infants, while also evaluating key potential confounding, explanatory and modifying covariates. Overall, 9.0% of infants were born prematurely, 14.0% of infants were LBW and 22.9% were SGA. LBW infants had significantly increased odds of stunting, wasting and underweight persisting to 12 months of age, and SGA infants had significantly increased odds of stunting and underweight. LBW and SGA infants had higher rates of weight-for-length gain in the first month of life. Maternal educational attainment and exclusive breastfeeding decreased the risk of stunting and undernutrition. In this setting, LBW and SGA infants have higher rates of growth stunting and undernutrition during the first year of life and do not exhibit catch-up growth by 12 months of age. Clinical Trial Registration NCT00486863
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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