Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study

Jaya Chakravarty, Epco Hasker, Sangeeta Kansal, Om Prakash Singh, Paritosh Malaviya, Abhishek Kumar Singh, Ankita Chourasia, Toolika Singh, Medhavi Sudarshan, Akhil Pratap Singh, Bhawana Singh, Rudra Pratap Singh, Bart Ostyn, Michaela Fakiola, Albert Picado, Joris Menten, Jenefer M. Blackwell, Mary E. Wilson, David Sacks, Marleen Boelaert & 1 others Shyam Sundar

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2 Citations (Scopus)

Abstract

BACKGROUND: Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). METHODS: We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6-12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. RESULTS: Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1-8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. CONCLUSION: We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated.

Original languageEnglish
Pages (from-to)e0007216
JournalPLoS Neglected Tropical Diseases
Volume13
Issue number3
DOIs
Publication statusPublished - 1 Mar 2019

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Asymptomatic Infections
Visceral Leishmaniasis
Cohort Studies
Leishmania donovani
Enzyme-Linked Immunosorbent Assay
Asymptomatic Diseases
Antibodies
Infection
Genetic Markers
Single Nucleotide Polymorphism
Disease Progression
India
Odds Ratio
Polymerase Chain Reaction

Cite this

Chakravarty, J., Hasker, E., Kansal, S., Singh, O. P., Malaviya, P., Singh, A. K., ... Sundar, S. (2019). Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study. PLoS Neglected Tropical Diseases, 13(3), e0007216. https://doi.org/10.1371/journal.pntd.0007216
Chakravarty, Jaya ; Hasker, Epco ; Kansal, Sangeeta ; Singh, Om Prakash ; Malaviya, Paritosh ; Singh, Abhishek Kumar ; Chourasia, Ankita ; Singh, Toolika ; Sudarshan, Medhavi ; Singh, Akhil Pratap ; Singh, Bhawana ; Singh, Rudra Pratap ; Ostyn, Bart ; Fakiola, Michaela ; Picado, Albert ; Menten, Joris ; Blackwell, Jenefer M. ; Wilson, Mary E. ; Sacks, David ; Boelaert, Marleen ; Sundar, Shyam. / Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis : A cohort study. In: PLoS Neglected Tropical Diseases. 2019 ; Vol. 13, No. 3. pp. e0007216.
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title = "Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study",
abstract = "BACKGROUND: Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). METHODS: We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6-12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. RESULTS: Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95{\%} CI 1.1-8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. CONCLUSION: We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated.",
author = "Jaya Chakravarty and Epco Hasker and Sangeeta Kansal and Singh, {Om Prakash} and Paritosh Malaviya and Singh, {Abhishek Kumar} and Ankita Chourasia and Toolika Singh and Medhavi Sudarshan and Singh, {Akhil Pratap} and Bhawana Singh and Singh, {Rudra Pratap} and Bart Ostyn and Michaela Fakiola and Albert Picado and Joris Menten and Blackwell, {Jenefer M.} and Wilson, {Mary E.} and David Sacks and Marleen Boelaert and Shyam Sundar",
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Chakravarty, J, Hasker, E, Kansal, S, Singh, OP, Malaviya, P, Singh, AK, Chourasia, A, Singh, T, Sudarshan, M, Singh, AP, Singh, B, Singh, RP, Ostyn, B, Fakiola, M, Picado, A, Menten, J, Blackwell, JM, Wilson, ME, Sacks, D, Boelaert, M & Sundar, S 2019, 'Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis: A cohort study' PLoS Neglected Tropical Diseases, vol. 13, no. 3, pp. e0007216. https://doi.org/10.1371/journal.pntd.0007216

Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis : A cohort study. / Chakravarty, Jaya; Hasker, Epco; Kansal, Sangeeta; Singh, Om Prakash; Malaviya, Paritosh; Singh, Abhishek Kumar; Chourasia, Ankita; Singh, Toolika; Sudarshan, Medhavi; Singh, Akhil Pratap; Singh, Bhawana; Singh, Rudra Pratap; Ostyn, Bart; Fakiola, Michaela; Picado, Albert; Menten, Joris; Blackwell, Jenefer M.; Wilson, Mary E.; Sacks, David; Boelaert, Marleen; Sundar, Shyam.

In: PLoS Neglected Tropical Diseases, Vol. 13, No. 3, 01.03.2019, p. e0007216.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Determinants for progression from asymptomatic infection to symptomatic visceral leishmaniasis

T2 - A cohort study

AU - Chakravarty, Jaya

AU - Hasker, Epco

AU - Kansal, Sangeeta

AU - Singh, Om Prakash

AU - Malaviya, Paritosh

AU - Singh, Abhishek Kumar

AU - Chourasia, Ankita

AU - Singh, Toolika

AU - Sudarshan, Medhavi

AU - Singh, Akhil Pratap

AU - Singh, Bhawana

AU - Singh, Rudra Pratap

AU - Ostyn, Bart

AU - Fakiola, Michaela

AU - Picado, Albert

AU - Menten, Joris

AU - Blackwell, Jenefer M.

AU - Wilson, Mary E.

AU - Sacks, David

AU - Boelaert, Marleen

AU - Sundar, Shyam

PY - 2019/3/1

Y1 - 2019/3/1

N2 - BACKGROUND: Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). METHODS: We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6-12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. RESULTS: Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1-8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. CONCLUSION: We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated.

AB - BACKGROUND: Asymptomatic Leishmania donovani infections outnumber clinical presentations, however the predictors for development of active disease are not well known. We aimed to identify serological, immunological and genetic markers for progression from L. donovani infection to clinical Visceral Leishmaniasis (VL). METHODS: We enrolled all residents >2 years of age in 27 VL endemic villages in Bihar (India). Blood samples collected on filter paper on two occasions 6-12 months apart, were tested for antibodies against L. donovani with rK39-ELISA and DAT. Sero converters, (negative for both tests in the first round but positive on either of the two during the second round) and controls (negative on both tests on both occasions) were followed for three years. At the start of follow-up venous blood was collected for the following tests: DAT, rK39- ELISA, Quantiferon assay, SNP/HLA genotyping and L.donovani specific quantitative PCR. RESULTS: Among 1,606 subjects enrolled,17 (8/476 seroconverters and 9/1,130 controls) developed VL (OR 3.1; 95% CI 1.1-8.3). High DAT and rK39 ELISA antibody titers as well as positive qPCR were strongly and significantly associated with progression from seroconversion to VL with odds ratios of 19.1, 30.3 and 20.9 respectively. Most VL cases arose early (median 5 months) during follow-up. CONCLUSION: We confirmed the strong association between high DAT and/or rK39 titers and progression to disease among asymptomatic subjects and identified qPCR as an additional predictor. Low predictive values do not warrant prophylactic treatment but as most progressed to VL early during follow-up, careful oberservation of these subjects for at least 6 months is indicated.

UR - http://www.scopus.com/inward/record.url?scp=85064577457&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0007216

DO - 10.1371/journal.pntd.0007216

M3 - Article

VL - 13

SP - e0007216

JO - P L o S NEGLECTED TROPICAL DISEASES

JF - P L o S NEGLECTED TROPICAL DISEASES

SN - 1935-2727

IS - 3

ER -