Visceral leishmaniasis IgG1 rapid monitoring of cure vs. relapse, and potential for diagnosis of post kala-azar dermal leishmaniasis

Tegwen Marlais; Tapan Bhattacharyya; Om Prakash Singh; Pascal Mertens; Quentin Gilleman; Caroline Thunissen; Bruno C. Bremer Hinckel; Callum Pearson; Bathsheba L. Gardner; Stephanie Airs; Marianne de la Roche; Kiera Hayes; Hannah Hafezi; Andrew K. Falconar; Osama Eisa; Alfarazdeg Saad; Basudha Khanal; Narayan Raj Bhattarai; Suman Rijal; Marleen Boelaert; Sayda El-Safi; Shyam Sundar; Michael A. Miles

doi:10.3389/fcimb.2018.00427

Visceral leishmaniasis IgG1 rapid monitoring of cure vs. relapse, and potential for diagnosis of post kala-azar dermal leishmaniasis

Tegwen Marlais, Tapan Bhattacharyya, Om Prakash Singh, Pascal Mertens, Quentin Gilleman, Caroline Thunissen, Bruno C. Bremer Hinckel, Callum Pearson, Bathsheba L. Gardner, Stephanie Airs, Marianne de la Roche, Kiera Hayes, Hannah Hafezi, Andrew K. Falconar, Osama Eisa, Alfarazdeg Saad, Basudha Khanal, Narayan Raj Bhattarai, Suman Rijal, Marleen BoelaertSayda El-Safi, Shyam Sundar, Michael A. Miles

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Abstract

Background: There is a recognized need for an improved diagnostic test to assess post-chemotherapeutic treatment outcome in visceral leishmaniasis (VL) and to diagnose post kala-azar dermal leishmaniasis (PKDL). We previously demonstrated by ELISA and a prototype novel rapid diagnostic test (RDT), that high anti-Leishmania IgG1 is associated with post-treatment relapse versus cure in VL.

Methodology: Here, we further evaluate this novel, low-cost RDT, named VL Sero K-SeT, and ELISA for monitoring IgG1 levels in VL patients after treatment. IgG1 levels against L. donovani lysate were determined. We applied these assays to Indian sera from cured VL at 6 months post treatment as well as to relapse and PKDL patients. Sudanese sera from pre- and post-treatment and relapse were also tested.

Results: Of 104 paired Indian sera taken before and after treatment for VL, when deemed clinically cured, 81 (77.9%) were positive by VL Sero K-SeT before treatment; by 6 months, 68 of these 81 (84.0%) had a negative or reduced RDT test line intensity. ELISAs differed in positivity rate between pre- and post-treatment (p = 0.0162). Twenty eight of 33 (84.8%) Indian samples taken at diagnosis of relapse were RDT positive. A comparison of Indian VL Sero K-SeT data from patients deemed cured and relapsed confirmed that there was a significant difference (p <0.0001) in positivity rate for the two groups using this RDT. Ten of 17 (58.8%) Sudanese sera went from positive to negative or decreased VL Sero K-SeT at the end of 11-30 days of treatment. Forty nine of 63 (77.8%) PKDL samples from India were positive by VL Sero K-SeT.

Conclusion: We have further shown the relevance of IgG1 in determining clinical status in VL patients. A positive VL Sero K-SeT may also be helpful in supporting diagnosis of PKDL. With further refinement, such as the use of specific antigens, the VL Sero K-SeT and/or IgG1 ELISA may be adjuncts to current VL control programmes.

Original language	English
Article number	427
Journal	Frontiers in Cellular and Infection Microbiology
Volume	8
Number of pages	10
ISSN	2235-2988
DOIs	https://doi.org/10.3389/fcimb.2018.00427
Publication status	Published - 2018

Keywords

visceral leishmaniasis
serology
treatment
relapse
cure
IgG1
RDT
PKDL
SEROLOGICAL MARKERS
NATURAL-HISTORY
BIHAR
INFECTION
MILTEFOSINE
HOUSEHOLDS
INFANTUM
AREAS
TESTS

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Marlais, T., Bhattacharyya, T., Singh, O. P., Mertens, P., Gilleman, Q., Thunissen, C., Hinckel, B. C. B., Pearson, C., Gardner, B. L., Airs, S., de la Roche, M., Hayes, K., Hafezi, H., Falconar, A. K., Eisa, O., Saad, A., Khanal, B., Bhattarai, N. R., Rijal, S., ... Miles, M. A. (2018). Visceral leishmaniasis IgG1 rapid monitoring of cure vs. relapse, and potential for diagnosis of post kala-azar dermal leishmaniasis. Frontiers in Cellular and Infection Microbiology, 8, Article 427. https://doi.org/10.3389/fcimb.2018.00427

@article{a1e4cfef5ebf4b08926afcbbaef20553,

title = "Visceral leishmaniasis IgG1 rapid monitoring of cure vs. relapse, and potential for diagnosis of post kala-azar dermal leishmaniasis",

abstract = "Background: There is a recognized need for an improved diagnostic test to assess post-chemotherapeutic treatment outcome in visceral leishmaniasis (VL) and to diagnose post kala-azar dermal leishmaniasis (PKDL). We previously demonstrated by ELISA and a prototype novel rapid diagnostic test (RDT), that high anti-Leishmania IgG1 is associated with post-treatment relapse versus cure in VL.Methodology: Here, we further evaluate this novel, low-cost RDT, named VL Sero K-SeT, and ELISA for monitoring IgG1 levels in VL patients after treatment. IgG1 levels against L. donovani lysate were determined. We applied these assays to Indian sera from cured VL at 6 months post treatment as well as to relapse and PKDL patients. Sudanese sera from pre- and post-treatment and relapse were also tested.Results: Of 104 paired Indian sera taken before and after treatment for VL, when deemed clinically cured, 81 (77.9%) were positive by VL Sero K-SeT before treatment; by 6 months, 68 of these 81 (84.0%) had a negative or reduced RDT test line intensity. ELISAs differed in positivity rate between pre- and post-treatment (p = 0.0162). Twenty eight of 33 (84.8%) Indian samples taken at diagnosis of relapse were RDT positive. A comparison of Indian VL Sero K-SeT data from patients deemed cured and relapsed confirmed that there was a significant difference (p <0.0001) in positivity rate for the two groups using this RDT. Ten of 17 (58.8%) Sudanese sera went from positive to negative or decreased VL Sero K-SeT at the end of 11-30 days of treatment. Forty nine of 63 (77.8%) PKDL samples from India were positive by VL Sero K-SeT.Conclusion: We have further shown the relevance of IgG1 in determining clinical status in VL patients. A positive VL Sero K-SeT may also be helpful in supporting diagnosis of PKDL. With further refinement, such as the use of specific antigens, the VL Sero K-SeT and/or IgG1 ELISA may be adjuncts to current VL control programmes.",

keywords = "visceral leishmaniasis, serology, treatment, relapse, cure, IgG1, RDT, PKDL, SEROLOGICAL MARKERS, NATURAL-HISTORY, BIHAR, INFECTION, MILTEFOSINE, HOUSEHOLDS, INFANTUM, AREAS, TESTS",

author = "Tegwen Marlais and Tapan Bhattacharyya and Singh, {Om Prakash} and Pascal Mertens and Quentin Gilleman and Caroline Thunissen and Hinckel, {Bruno C. Bremer} and Callum Pearson and Gardner, {Bathsheba L.} and Stephanie Airs and {de la Roche}, Marianne and Kiera Hayes and Hannah Hafezi and Falconar, {Andrew K.} and Osama Eisa and Alfarazdeg Saad and Basudha Khanal and Bhattarai, {Narayan Raj} and Suman Rijal and Marleen Boelaert and Sayda El-Safi and Shyam Sundar and Miles, {Michael A.}",

note = "FTX; DOAJ",

year = "2018",

doi = "10.3389/fcimb.2018.00427",

language = "English",

volume = "8",

journal = "Frontiers in Cellular and Infection Microbiology",

issn = "2235-2988",

publisher = "Frontiers Media S. A.",

}

Marlais, T, Bhattacharyya, T, Singh, OP, Mertens, P, Gilleman, Q, Thunissen, C, Hinckel, BCB, Pearson, C, Gardner, BL, Airs, S, de la Roche, M, Hayes, K, Hafezi, H, Falconar, AK, Eisa, O, Saad, A, Khanal, B, Bhattarai, NR, Rijal, S, Boelaert, M, El-Safi, S, Sundar, S & Miles, MA 2018, 'Visceral leishmaniasis IgG1 rapid monitoring of cure vs. relapse, and potential for diagnosis of post kala-azar dermal leishmaniasis', Frontiers in Cellular and Infection Microbiology, vol. 8, 427. https://doi.org/10.3389/fcimb.2018.00427

TY - JOUR

T1 - Visceral leishmaniasis IgG1 rapid monitoring of cure vs. relapse, and potential for diagnosis of post kala-azar dermal leishmaniasis

AU - Marlais, Tegwen

AU - Bhattacharyya, Tapan

AU - Singh, Om Prakash

AU - Mertens, Pascal

AU - Gilleman, Quentin

AU - Thunissen, Caroline

AU - Hinckel, Bruno C. Bremer

AU - Pearson, Callum

AU - Gardner, Bathsheba L.

AU - Airs, Stephanie

AU - de la Roche, Marianne

AU - Hayes, Kiera

AU - Hafezi, Hannah

AU - Falconar, Andrew K.

AU - Eisa, Osama

AU - Saad, Alfarazdeg

AU - Khanal, Basudha

AU - Bhattarai, Narayan Raj

AU - Rijal, Suman

AU - Boelaert, Marleen

AU - El-Safi, Sayda

AU - Sundar, Shyam

AU - Miles, Michael A.

N1 - FTX; DOAJ

PY - 2018

Y1 - 2018

N2 - Background: There is a recognized need for an improved diagnostic test to assess post-chemotherapeutic treatment outcome in visceral leishmaniasis (VL) and to diagnose post kala-azar dermal leishmaniasis (PKDL). We previously demonstrated by ELISA and a prototype novel rapid diagnostic test (RDT), that high anti-Leishmania IgG1 is associated with post-treatment relapse versus cure in VL.Methodology: Here, we further evaluate this novel, low-cost RDT, named VL Sero K-SeT, and ELISA for monitoring IgG1 levels in VL patients after treatment. IgG1 levels against L. donovani lysate were determined. We applied these assays to Indian sera from cured VL at 6 months post treatment as well as to relapse and PKDL patients. Sudanese sera from pre- and post-treatment and relapse were also tested.Results: Of 104 paired Indian sera taken before and after treatment for VL, when deemed clinically cured, 81 (77.9%) were positive by VL Sero K-SeT before treatment; by 6 months, 68 of these 81 (84.0%) had a negative or reduced RDT test line intensity. ELISAs differed in positivity rate between pre- and post-treatment (p = 0.0162). Twenty eight of 33 (84.8%) Indian samples taken at diagnosis of relapse were RDT positive. A comparison of Indian VL Sero K-SeT data from patients deemed cured and relapsed confirmed that there was a significant difference (p <0.0001) in positivity rate for the two groups using this RDT. Ten of 17 (58.8%) Sudanese sera went from positive to negative or decreased VL Sero K-SeT at the end of 11-30 days of treatment. Forty nine of 63 (77.8%) PKDL samples from India were positive by VL Sero K-SeT.Conclusion: We have further shown the relevance of IgG1 in determining clinical status in VL patients. A positive VL Sero K-SeT may also be helpful in supporting diagnosis of PKDL. With further refinement, such as the use of specific antigens, the VL Sero K-SeT and/or IgG1 ELISA may be adjuncts to current VL control programmes.

AB - Background: There is a recognized need for an improved diagnostic test to assess post-chemotherapeutic treatment outcome in visceral leishmaniasis (VL) and to diagnose post kala-azar dermal leishmaniasis (PKDL). We previously demonstrated by ELISA and a prototype novel rapid diagnostic test (RDT), that high anti-Leishmania IgG1 is associated with post-treatment relapse versus cure in VL.Methodology: Here, we further evaluate this novel, low-cost RDT, named VL Sero K-SeT, and ELISA for monitoring IgG1 levels in VL patients after treatment. IgG1 levels against L. donovani lysate were determined. We applied these assays to Indian sera from cured VL at 6 months post treatment as well as to relapse and PKDL patients. Sudanese sera from pre- and post-treatment and relapse were also tested.Results: Of 104 paired Indian sera taken before and after treatment for VL, when deemed clinically cured, 81 (77.9%) were positive by VL Sero K-SeT before treatment; by 6 months, 68 of these 81 (84.0%) had a negative or reduced RDT test line intensity. ELISAs differed in positivity rate between pre- and post-treatment (p = 0.0162). Twenty eight of 33 (84.8%) Indian samples taken at diagnosis of relapse were RDT positive. A comparison of Indian VL Sero K-SeT data from patients deemed cured and relapsed confirmed that there was a significant difference (p <0.0001) in positivity rate for the two groups using this RDT. Ten of 17 (58.8%) Sudanese sera went from positive to negative or decreased VL Sero K-SeT at the end of 11-30 days of treatment. Forty nine of 63 (77.8%) PKDL samples from India were positive by VL Sero K-SeT.Conclusion: We have further shown the relevance of IgG1 in determining clinical status in VL patients. A positive VL Sero K-SeT may also be helpful in supporting diagnosis of PKDL. With further refinement, such as the use of specific antigens, the VL Sero K-SeT and/or IgG1 ELISA may be adjuncts to current VL control programmes.

KW - visceral leishmaniasis

KW - serology

KW - treatment

KW - relapse

KW - cure

KW - IgG1

KW - RDT

KW - PKDL

KW - SEROLOGICAL MARKERS

KW - NATURAL-HISTORY

KW - BIHAR

KW - INFECTION

KW - MILTEFOSINE

KW - HOUSEHOLDS

KW - INFANTUM

KW - AREAS

KW - TESTS

U2 - 10.3389/fcimb.2018.00427

DO - 10.3389/fcimb.2018.00427

M3 - A1: Web of Science-article

SN - 2235-2988

VL - 8

JO - Frontiers in Cellular and Infection Microbiology

JF - Frontiers in Cellular and Infection Microbiology

M1 - 427

ER -

Visceral leishmaniasis IgG1 rapid monitoring of cure vs. relapse, and potential for diagnosis of post kala-azar dermal leishmaniasis

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Keywords

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