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A combination of two ELISA tests for nasopharyngeal carcinoma screening in endemic areas based on a case-control study.

ABSTRACT: For populations with a high risk of nasopharyngeal carcinoma (NPC) in Guangdong province in southern China, mass screening is the first choice to prevent death from NPC. To improve the performance of NPC screening, we used a combination based on the IgA antibody against the Epstein-Barr virus (EBV) capsid antigen (VCA-IgA) and the IgA antibody against Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA) to NPC screening by enzyme-linked immunosorbent assay (ELISA). A multiplication model was applied to measure the level of the combination. We evaluated the NPC screening effect of the markers.A case-control study was performed to assess the NPC screening effect of the markers. A total of 10,894 serum specimens were collected, including 554 samples from NPC patients and 10,340 samples from healthy controls. In the training stage, 640 subjects were randomly selected, including 320 NPC cases and 320 healthy controls. In the verification stage, 10,254 subjects were used to verify the NPC screening effect of the combination. Receiver operating characteristic (ROC) analysis was performed. In the verification stage, the combination achieved an sensitivity of 91.45%, a specificity of 93.45%, and an area under the ROC curve (AUC) of 0.978 (95% CI [0.968-0.987]). Compared with VCA-IgA and EBNA1-IgA individually, the combination had an improved screening performance. A probability (PROB) calculated by logistic regression model based on VCA-IgA and EBNA1-IgA was applied to NPC screening by ELISA in China. The AUC of the combination was a little bit larger than the PROB. There was a slight increase (3.13%) in the sensitivity of the combination compared to the sensitivity of the PROB, while the specificity was lower for the combination (92.50%) than for the PROB (95.94%). We successfully applied a combination of two ELISA tests based on VCA-IgA and EBNA1-IgA for NPC screening by using a multiplication model. The results suggested that the combination was effective and can be an option for NPC screening.

SUBMITTER: Rao D

PROVIDER: S-EPMC7666820 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A combination of two ELISA tests for nasopharyngeal carcinoma screening in endemic areas based on a case-control study.

Rao Dongping D Fu Meiqin M Chen Yingjie Y Liu Qing Q Xiao Lin L Zhang Xin X Li Zhongxiao Z Li Haitao H He Yongyi Y Chen Yongxing Y Chen Jieying J Hu Jin J Huang Yanming Y

PeerJ 20201112

For populations with a high risk of nasopharyngeal carcinoma (NPC) in Guangdong province in southern China, mass screening is the first choice to prevent death from NPC. To improve the performance of NPC screening, we used a combination based on the IgA antibody against the Epstein-Barr virus (EBV) capsid antigen (VCA-IgA) and the IgA antibody against Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA) to NPC screening by enzyme-linked immunosorbent assay (ELISA). A multiplication model was applied ...[more]

PMID: 33240616

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Project description:BACKGROUND:Infection with Schistosoma mansoni is a major cause of morbidity and mortality in endemic areas, and is increasingly diagnosed in migrants and travellers outside transmission areas. Markers for the assessment of morbidity and impact of control programs in endemic areas and for the clinical management of patients in the clinical setting are scant, especially for intestinal involvement. Ultrasonography is well established to evaluate hepatosplenic pathology; on the contrary, ultrasound evaluation of intestinal schistosomiasis is virtually unexplored. In this pilot study, we aimed to describe and evaluate the accuracy of unenhanced intestinal ultrasound for morbidity due to intestinal S. mansoni infection. METHODOLOGY/PRINCIPAL FINDINGS:We performed a blind case-control study of unenhanced intestinal ultrasound on 107 adults accessing the outpatient clinic of our Centre for Tropical Diseases between January-July 2018 as part of a screening for tropical diseases in migrants and travellers returning from endemic areas. Other clinical and laboratory data were obtained routine examination reports. We could not find any overtly pathological thickness of the gut wall in the sigma, proximal ascending colon, and terminal ileum, in patients with S. mansoni infection (n = 17), S. haematobium infection (n = 7), positive anti-Schistosoma serology (n = 31), and uninfected individuals (n = 52), with no difference among groups as assessed by ANOVA. No polyps or other intestinal abnormalities were visualized. There was no significant change in gut wall thickness one month after treatment with praziquantel in patients with S. mansoni infection (n = 11). CONCLUSIONS/SIGNIFICANCE:Our preliminary results suggest that intestinal ultrasound might not be a sensitive tool for detecting minor intestinal morbidity due to schistosomiasis. Further studies in a hospital setting comparing colonoscopy and ultrasonography may be envisaged; in endemic areas, further studies are needed to describe and assess the usefulness of intestinal ultrasound in patients stratified by infection intensity and compared with markers such as calprotectin and fecal occult blood.

Project description:BackgroundEpstein-Barr virus (EBV) infection is a crucial risk factor for nasopharyngeal carcinoma (NPC), but the mechanism for its elevated activation level in NPC endemic areas remains unclear. This study aims to identify the EBV natural variations contributed to the different reactivation potential between NPC endemic and non-endemic areas.Methods1030 subjects were recruited in China, including 303 healthy individuals from two NPC non-endemic areas, 483 healthy people from three endemic areas and 244 NPC patients. Among which, saliva DNA samples from 244 participants were sequenced for the EBV immediate early (IE) genes of BRLF1 and BZLF1, their promoters were included; the rest 786 subjects were used for the validation of significant variations among three different populations. Haplotype and population structure analysis were conducted. Dual-luciferase assay was used to detect the promoter activity.ResultsA total of 246 distinct variations were detected, 29 showed significant difference in the frequencies between healthy people from NPC endemic area and non-endemic area. Population structure analysis clustered EBV strains into 9 subgroups mostly in accordance with the geographical origin of samples. Interestingly, two EBV genotypes, Rp-V1 and Rp-V2, were identified according to the linkage relationship of the variations in BRLF1 promoter (Rp). Rp-V1 has higher frequency in NPC endemic areas than in non-endemic areas (52.38% vs 18.15%, P = 2.07 × 10-14), and was associated with higher oral EBV DNA levels (adjusted OR = 1.64, 95% CI = 1.21-2.24, P = .002), suggesting a more powerful activation ability of Rp-V1 than that of the prototype Rp-of the EBV strain; On the contrary, Rp-V2 has higher frequency in NPC non-endemic areas than in endemic areas (18.48% vs 0.38%, P = 1.17 × 10-7), might represent a reduced activation potential of EBV. Further dual-luciferase assay showed Rp-V1 has higher promoter activity while compared with Rp-V2 (P < .0001). Notably, Rp-V1 impaired the transcription repression effect of YY1 while Rp-V2 strengthened the transcription repression effect of EBF1 on Rp. In addition, significant differences of Rta 393-407 CTL epitope which may influence the recognition of Rta by CD8+ T cells were detected between healthy people from NPC endemic area and non-endemic area.ConclusionsThis study identified natural variations in cis-acting elements (YY1 and EBF1) of EBV Rp altering Rp transcription activities, which may contribute to the elevated EBV activation level in NPC endemic areas than non-endemic areas.

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A combination of two ELISA tests for nasopharyngeal carcinoma screening in endemic areas based on a case-control study.

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A combination of two ELISA tests for nasopharyngeal carcinoma screening in endemic areas based on a case-control study.

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