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- Title
Conversion of asymptomatic infection to symptomatic visceral leishmaniasis: A study of possible immunological markers.
- Authors
Rabi Das, Vidya Nand; Bimal, Sanjiva; Siddiqui, Niyamat Ali; Kumar, Ashish; Pandey, Krishna; Sinha, Sanjay Kumar; Topno, Roshan Kamal; Mahentesh, Vijay; Singh, Ashish Kumar; Lal, Chandra Shekhar; Singh, Subhankar Kumar; Das, Pradeep
- Abstract
Introduction: Presence of asymptomatic individualsin endemic areas is common. The possible biomarkers inasymptomatic individualspatients 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 rK39sero-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 individualssubjects identified at base-line. The level of ADA, IL-10 and IFN-γ remained consistently high in asymptomatic individuals and amongst these, ADA and IL-10 but not IFN-γ remained higher at the development of clinical symptoms into active VL suspects. 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 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. Author summary: 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.donovaniinfection, 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.
- Subjects
SOUTH Asia; BIHAR (India); INDIA; VISCERAL leishmaniasis; ADENOSINE deaminase; INTERFERON gamma; DISEASE eradication; INFECTION
- Publication
PLoS Neglected Tropical Diseases, 2020, Vol 14, Issue 6, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0008272