Conversion of asymptomatic infection to symptomatic visceral leishmaniasis: A study of possible immunological markers
Introduction Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL)...
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| Published in | PLoS neglected tropical diseases Vol. 14; no. 6; p. e0008272 |
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| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Public Library of Science
18.06.2020
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| Abstract | Introduction Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39.sup.+ sorted direct agglutination test positive (DAT.sup.+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-[gamma]), Tumour Necrosis Factor alpha (TNF-[alpha]) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL. Methods Sample size was 5794 healthy individuals from VL endemic region. Antibody tests(DAT &rK39) were performed and later a qPCR assay was employed using kDNA specific primers and probes. Immunological biomarkers examined were ADA level by ADA-MTP kit and quantitative cytokines(IFN-[gamma], IL-10 and TNF-[alpha]) by ELISA. Results 120 asymptomatic individuals of 308 rK39 sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individuals identified at base-line. The level of ADA, IL-10 and IFN-[gamma] remained consistently high in asymptomatic cases and amongst these, ADA and IL-10 but not IFN-[gamma] remained higher at the development of clinical symptoms into active VL. On the contrary, there was no significant change in the mean concentration of TNF-[alpha] at both stages of the disease. Discussion We surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and may play a crucial role in transmission of visceral leishmaniasis in endemic areas. The data also suggests that ADA and IL-10 can serve as a potential biomarker during the conversion of asymptomatic into symptomatic VL. |
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| AbstractList | INTRODUCTIONPresence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39+sorted direct agglutination test positive (DAT+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-γ), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL. METHODSSample size was 5794 healthy individuals from VL endemic region. Antibody tests(DAT &rK39) were performed and later a qPCR assay was employed using kDNA specific primers and probes. Immunological biomarkers examined were ADA level by ADA-MTP kit and quantitative cytokines(IFN-γ, IL-10 and TNF-α) by ELISA. RESULTS120 asymptomatic individuals of 308 rK39 sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individuals identified at base-line. The level of ADA, IL-10 and IFN-γ remained consistently high in asymptomatic cases and amongst these, ADA and IL-10 but not IFN-γ remained higher at the development of clinical symptoms into active VL. On the contrary, there was no significant change in the mean concentration of TNF-α at both stages of the disease. DISCUSSIONWe surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and may play a crucial role in transmission of visceral leishmaniasis in endemic areas. The data also suggests that ADA and IL-10 can serve as a potential biomarker during the conversion of asymptomatic into symptomatic VL. Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39.sup.+ sorted direct agglutination test positive (DAT.sup.+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-[gamma]), Tumour Necrosis Factor alpha (TNF-[alpha]) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL. 120 asymptomatic individuals of 308 rK39 sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individuals identified at base-line. The level of ADA, IL-10 and IFN-[gamma] remained consistently high in asymptomatic cases and amongst these, ADA and IL-10 but not IFN-[gamma] remained higher at the development of clinical symptoms into active VL. On the contrary, there was no significant change in the mean concentration of TNF-[alpha] at both stages of the disease. We surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and may play a crucial role in transmission of visceral leishmaniasis in endemic areas. The most threatening form of leishmaniasis is human visceral leishmaniasis, which is caused by L . donovani in Indian subcontinent. The disease accounts for huge annual burden of infectious disease in India. Efforts towards disease elimination programme are far beyond satisfaction and there is need to re-strengthen health monitoring, surveillance programme in endemic areas. There is a greater need to identify asymptomatic individuals amongst endemic healthy control by active surveillance programme. Further, except a few, many asymptomatic subjects become sero-negative without developing VL due to strong inherent cellular immunity possessed by them. This study enumerates use of rK39, DAT and quantitative PCR(qPCR) in asymptomatic detection and then evaluate immunological biomarkers(Adenosine deaminase, IFN-γ, TNF-α and IL-10) which help in disease conversion to symptomatic VL, at 6 month follow- up. Follow–up analysis revealed that antibody testing with rK39 (3.24%), DAT (8.33%) had poor agreement with disease conversion. By qPCR, we could identify the level of parasitemia, and collectively with serology, the test detected 23.80% of asymptomatic cases converted into disease. The level of ADA and IL-10 remained consistently high during conversion. IFN-γ became high in asymptomatic infection but became low on conversion, whereas, no significant change in level of TNF-α was observed at both stages of disease. Thus by use of qPCR, concomitantly with DAT over rK39 + sorted endemic healthy control may be employed for early case detection. Adenosine is produced by ecto-nucleotide during L . donovani infection, has been previously reported and in parallel to this study we conclude that determination of adenosine deaminase level (ADA) might help identify early cases with more tendency to convert into disease. This will help to boost health monitoring programme to eradicate Kala-azar in Bihar, India. Introduction Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39.sup.+ sorted direct agglutination test positive (DAT.sup.+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-[gamma]), Tumour Necrosis Factor alpha (TNF-[alpha]) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL. Methods Sample size was 5794 healthy individuals from VL endemic region. Antibody tests(DAT &rK39) were performed and later a qPCR assay was employed using kDNA specific primers and probes. Immunological biomarkers examined were ADA level by ADA-MTP kit and quantitative cytokines(IFN-[gamma], IL-10 and TNF-[alpha]) by ELISA. Results 120 asymptomatic individuals of 308 rK39 sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individuals identified at base-line. The level of ADA, IL-10 and IFN-[gamma] remained consistently high in asymptomatic cases and amongst these, ADA and IL-10 but not IFN-[gamma] remained higher at the development of clinical symptoms into active VL. On the contrary, there was no significant change in the mean concentration of TNF-[alpha] at both stages of the disease. Discussion We surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and may play a crucial role in transmission of visceral leishmaniasis in endemic areas. The data also suggests that ADA and IL-10 can serve as a potential biomarker during the conversion of asymptomatic into symptomatic VL. Introduction Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39+sorted direct agglutination test positive (DAT+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-γ), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL. Methods Sample size was 5794 healthy individuals from VL endemic region. Antibody tests(DAT &rK39) were performed and later a qPCR assay was employed using kDNA specific primers and probes. Immunological biomarkers examined were ADA level by ADA–MTP kit and quantitative cytokines(IFN-γ, IL-10 and TNF-α) by ELISA. Results 120 asymptomatic individuals of 308 rK39 sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individuals identified at base-line. The level of ADA, IL-10 and IFN-γ remained consistently high in asymptomatic cases and amongst these, ADA and IL-10 but not IFN-γ remained higher at the development of clinical symptoms into active VL. On the contrary, there was no significant change in the mean concentration of TNF-α at both stages of the disease. Discussion We surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and may play a crucial role in transmission of visceral leishmaniasis in endemic areas. The data also suggests that ADA and IL-10 can serve as a potential biomarker during the conversion of asymptomatic into symptomatic VL. Introduction Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39+sorted direct agglutination test positive (DAT+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-γ), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL. Methods Sample size was 5794 healthy individuals from VL endemic region. Antibody tests(DAT &rK39) were performed and later a qPCR assay was employed using kDNA specific primers and probes. Immunological biomarkers examined were ADA level by ADA–MTP kit and quantitative cytokines(IFN-γ, IL-10 and TNF-α) by ELISA. Results 120 asymptomatic individuals of 308 rK39 sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individuals identified at base-line. The level of ADA, IL-10 and IFN-γ remained consistently high in asymptomatic cases and amongst these, ADA and IL-10 but not IFN-γ remained higher at the development of clinical symptoms into active VL. On the contrary, there was no significant change in the mean concentration of TNF-α at both stages of the disease. Discussion We surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and may play a crucial role in transmission of visceral leishmaniasis in endemic areas. The data also suggests that ADA and IL-10 can serve as a potential biomarker during the conversion of asymptomatic into symptomatic VL. |
| Audience | Academic |
| Author | Bimal, Sanjiva Pandey, Krishna Topno, Roshan Kamal Lal, Chandra Shekhar Siddiqui, Niyamat Ali Mahentesh, Vijay Sinha, Sanjay Kumar Kumar, Ashish Singh, Ashish Kumar Das, Pradeep Das, Vidya Nand Rabi Singh, Subhankar Kumar |
| AuthorAffiliation | Rajendra Memorial Research Institute of Medical Science (ICMR), Patna, India Centro de Pesquisa Gonçalo Moniz-FIOCRUZ/BA, BRAZIL |
| AuthorAffiliation_xml | – name: Centro de Pesquisa Gonçalo Moniz-FIOCRUZ/BA, BRAZIL – name: Rajendra Memorial Research Institute of Medical Science (ICMR), Patna, India |
| Author_xml | – sequence: 1 fullname: Das, Vidya Nand Rabi – sequence: 2 fullname: Bimal, Sanjiva – sequence: 3 fullname: Siddiqui, Niyamat Ali – sequence: 4 fullname: Kumar, Ashish – sequence: 5 fullname: Pandey, Krishna – sequence: 6 fullname: Sinha, Sanjay Kumar – sequence: 7 fullname: Topno, Roshan Kamal – sequence: 8 fullname: Mahentesh, Vijay – sequence: 9 fullname: Singh, Ashish Kumar – sequence: 10 fullname: Lal, Chandra Shekhar – sequence: 11 fullname: Singh, Subhankar Kumar – sequence: 12 fullname: Das, Pradeep |
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| CitedBy_id | crossref_primary_10_1186_s13071_021_04622_8 crossref_primary_10_3390_microorganisms9040759 crossref_primary_10_1002_wnan_1675 crossref_primary_10_1016_j_actatropica_2021_106126 crossref_primary_10_1016_j_jmii_2022_06_003 crossref_primary_10_3389_fcimb_2021_623437 crossref_primary_10_1098_rsos_201960 crossref_primary_10_1016_j_jiph_2022_12_021 crossref_primary_10_3389_fcimb_2021_707619 crossref_primary_10_3390_microorganisms12020394 crossref_primary_10_3389_fimmu_2021_765684 crossref_primary_10_1186_s13071_022_05524_z crossref_primary_10_1038_s41598_024_64592_6 crossref_primary_10_1080_14737159_2021_1900736 crossref_primary_10_3390_microorganisms9030578 |
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| Snippet | Introduction Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to... Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well... INTRODUCTIONPresence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to... The most threatening form of leishmaniasis is human visceral leishmaniasis, which is caused by L . donovani in Indian subcontinent. The disease accounts for... IntroductionPresence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to... Introduction Presence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to... |
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| SubjectTerms | Adenosine Adenosine deaminase Agglutination Agglutination tests Antibodies Asymptomatic infection Biological markers Biology and Life Sciences Biomarkers Chromatography Conversion Cytokines Development and progression Diagnosis Diagnostic tests DNA ELISA Enzyme-linked immunosorbent assay Health aspects Identification Immune system Immunology Infections Interferon Interleukin 10 Interleukins Medicine and Health Sciences Necrosis Nucleotide sequence Parasites Parasitic diseases Patients PCR Physiological aspects Polymerase chain reaction Primers Research and Analysis Methods Signs and symptoms Supervision Symptoms Transmission Tropical diseases Tumor necrosis factor-α Tumors Vector-borne diseases Visceral leishmaniasis γ-Interferon |
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| Title | Conversion of asymptomatic infection to symptomatic visceral leishmaniasis: A study of possible immunological markers |
| URI | https://www.proquest.com/docview/2424467020 https://search.proquest.com/docview/2415301515 https://pubmed.ncbi.nlm.nih.gov/PMC7326279 https://doaj.org/article/3578c83ead7c4901a08d642dbee90f2f http://dx.doi.org/10.1371/journal.pntd.0008272 |
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