Skip to main content
Top
Published in: European Journal of Clinical Microbiology & Infectious Diseases 4/2015

01-04-2015 | Article

Specific antibody responses as indicators of treatment efficacy for visceral leishmaniasis

Authors: A. C. Vallur, A. Hailu, D. Mondal, C. Reinhart, H. Wondimu, Y. Tutterrow, H. W. Ghalib, S. G. Reed, M. S. Duthie

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 4/2015

Login to get access

Abstract

Acute visceral leishmaniasis (VL) is caused by infection with parasites of the Leishmania donovani complex and may be fatal if not treated. Early diagnosis and efficacious treatment are the keys to effective VL management and control. Novel regimens are being developed to overcome limitations in VL treatment options, which are currently restricted by high costs, severe systemic side effects, and unresponsiveness. Although simple and accurate serological tests are available to help confirm VL, none are suitable to monitor treatment efficacy and cure. Here, we confirm that serum antibody responses to the diagnostic antigens rK39 and rK28 are unaltered by treatment, but demonstrate that antibodies produced against two antigens, rK26 and rK18, can be used as an indirect measure of parasite clearance. The levels of anti-rK18 and -rK26 antibodies were high in patients at initial diagnosis but declined in patients treated with either SSG (Ethiopia) or AmBisome™ (Bangladesh). Taken together, we propose that serological tests which measure antibodies to rK26 and rK18 merit consideration as potential markers of treatment success and cure.
Literature
1.
go back to reference Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J et al (2012) Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7(5):e35671CrossRefPubMedCentralPubMed Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J et al (2012) Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7(5):e35671CrossRefPubMedCentralPubMed
2.
3.
go back to reference World Health Organization (WHO) (2010) Leishmaniasis: burden of disease, surveillance and control, epidemics, access to medicines, information resources World Health Organization (WHO) (2010) Leishmaniasis: burden of disease, surveillance and control, epidemics, access to medicines, information resources
4.
go back to reference Alvar J, Aparicio P, Aseffa A, Den Boer M, Cañavate C, Dedet JP et al (2008) The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 21(2):334–359, table of contentsCrossRefPubMedCentralPubMed Alvar J, Aparicio P, Aseffa A, Den Boer M, Cañavate C, Dedet JP et al (2008) The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 21(2):334–359, table of contentsCrossRefPubMedCentralPubMed
5.
go back to reference Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW et al (2007) Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol 5(11):873–882CrossRefPubMed Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW et al (2007) Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat Rev Microbiol 5(11):873–882CrossRefPubMed
6.
go back to reference Sundar S, Chakravarty J (2013) Leishmaniasis: an update of current pharmacotherapy. Expert Opin Pharmacother 14(1):53–63CrossRefPubMed Sundar S, Chakravarty J (2013) Leishmaniasis: an update of current pharmacotherapy. Expert Opin Pharmacother 14(1):53–63CrossRefPubMed
7.
go back to reference Freitas-Junior LH, Chatelain E, Kim HA, Siqueira-Neto JL (2012) Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it? Int J Parasitol Drugs Drug Resist 2:11–19CrossRefPubMedCentralPubMed Freitas-Junior LH, Chatelain E, Kim HA, Siqueira-Neto JL (2012) Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it? Int J Parasitol Drugs Drug Resist 2:11–19CrossRefPubMedCentralPubMed
8.
go back to reference Mondal S, Bhattacharya P, Ali N (2010) Current diagnosis and treatment of visceral leishmaniasis. Exp Rev Anti Infect Ther 8(8):919–944CrossRef Mondal S, Bhattacharya P, Ali N (2010) Current diagnosis and treatment of visceral leishmaniasis. Exp Rev Anti Infect Ther 8(8):919–944CrossRef
9.
go back to reference Mondal D, Khan MG (2011) Recent advances in post-kala-azar dermal leishmaniasis. Curr Opin Infect Dis 24(5):418–422CrossRefPubMed Mondal D, Khan MG (2011) Recent advances in post-kala-azar dermal leishmaniasis. Curr Opin Infect Dis 24(5):418–422CrossRefPubMed
10.
go back to reference van Griensven J, Ritmeijer K, Lynen L, Diro E (2014) Visceral leishmaniasis as an AIDS defining condition: towards consistency across WHO guidelines. PLoS Negl Trop Dis 8(7):e2916CrossRefPubMedCentralPubMed van Griensven J, Ritmeijer K, Lynen L, Diro E (2014) Visceral leishmaniasis as an AIDS defining condition: towards consistency across WHO guidelines. PLoS Negl Trop Dis 8(7):e2916CrossRefPubMedCentralPubMed
11.
go back to reference Cota GF, de Sousa MR, Demarqui FN, Rabello A (2012) The diagnostic accuracy of serologic and molecular methods for detecting visceral leishmaniasis in HIV infected patients: meta-analysis. PLoS Negl Trop Dis 6(5):e1665CrossRefPubMedCentralPubMed Cota GF, de Sousa MR, Demarqui FN, Rabello A (2012) The diagnostic accuracy of serologic and molecular methods for detecting visceral leishmaniasis in HIV infected patients: meta-analysis. PLoS Negl Trop Dis 6(5):e1665CrossRefPubMedCentralPubMed
12.
go back to reference Zijlstra EE, Musa AM, Khalil EA, el-Hassan IM, el-Hassan AM (2003) Post-kala-azar dermal leishmaniasis. Lancet Infect Dis 3(2):87–98CrossRefPubMed Zijlstra EE, Musa AM, Khalil EA, el-Hassan IM, el-Hassan AM (2003) Post-kala-azar dermal leishmaniasis. Lancet Infect Dis 3(2):87–98CrossRefPubMed
13.
go back to reference Singh S, Sharma U, Mishra J (2011) Post-kala-azar dermal leishmaniasis: recent developments. Int J Dermatol 50(9):1099–1108CrossRefPubMed Singh S, Sharma U, Mishra J (2011) Post-kala-azar dermal leishmaniasis: recent developments. Int J Dermatol 50(9):1099–1108CrossRefPubMed
15.
go back to reference Sudarshan M, Weirather JL, Wilson ME, Sundar S (2011) Study of parasite kinetics with antileishmanial drugs using real-time quantitative PCR in Indian visceral leishmaniasis. J Antimicrob Chemother 66:1751–1755CrossRefPubMedCentralPubMed Sudarshan M, Weirather JL, Wilson ME, Sundar S (2011) Study of parasite kinetics with antileishmanial drugs using real-time quantitative PCR in Indian visceral leishmaniasis. J Antimicrob Chemother 66:1751–1755CrossRefPubMedCentralPubMed
16.
go back to reference Sundar S, Maurya R, Singh RK, Bharti K, Chakravarty J, Parekh A et al (2006) Rapid, noninvasive diagnosis of visceral leishmaniasis in India: comparison of two immunochromatographic strip tests for detection of anti-K39 antibody. J Clin Microbiol 44(1):251–253CrossRefPubMedCentralPubMed Sundar S, Maurya R, Singh RK, Bharti K, Chakravarty J, Parekh A et al (2006) Rapid, noninvasive diagnosis of visceral leishmaniasis in India: comparison of two immunochromatographic strip tests for detection of anti-K39 antibody. J Clin Microbiol 44(1):251–253CrossRefPubMedCentralPubMed
17.
go back to reference Welch RJ, Anderson BL, Litwin CM (2008) Rapid immunochromatographic strip test for detection of anti-K39 immunoglobulin G antibodies for diagnosis of visceral leishmaniasis. Clin Vaccine Immunol 15(9):1483–1484CrossRefPubMedCentralPubMed Welch RJ, Anderson BL, Litwin CM (2008) Rapid immunochromatographic strip test for detection of anti-K39 immunoglobulin G antibodies for diagnosis of visceral leishmaniasis. Clin Vaccine Immunol 15(9):1483–1484CrossRefPubMedCentralPubMed
18.
go back to reference Pattabhi S, Whittle J, Mohamath R, El-Safi S, Moulton GG, Guderian JA et al (2010) Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. PLoS Negl Trop Dis 4(9). pii: e822 Pattabhi S, Whittle J, Mohamath R, El-Safi S, Moulton GG, Guderian JA et al (2010) Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. PLoS Negl Trop Dis 4(9). pii: e822
19.
go back to reference Vaish M, Bhatia A, Reed SG, Chakravarty J, Sundar S (2012) Evaluation of rK28 antigen for serodiagnosis of visceral Leishmaniasis in India. Clin Microbiol Infect 18(1):81–85CrossRefPubMedCentralPubMed Vaish M, Bhatia A, Reed SG, Chakravarty J, Sundar S (2012) Evaluation of rK28 antigen for serodiagnosis of visceral Leishmaniasis in India. Clin Microbiol Infect 18(1):81–85CrossRefPubMedCentralPubMed
20.
go back to reference Bezuneh A, Mukhtar M, Abdoun A, Teferi T, Takele Y, Diro E et al (2014) Comparison of point-of-care tests for the rapid diagnosis of visceral leishmaniasis in East African patients. Am J Trop Med Hyg. pii: 13-0759 Bezuneh A, Mukhtar M, Abdoun A, Teferi T, Takele Y, Diro E et al (2014) Comparison of point-of-care tests for the rapid diagnosis of visceral leishmaniasis in East African patients. Am J Trop Med Hyg. pii: 13-0759
21.
go back to reference Gidwani K, Picado A, Ostyn B, Singh SP, Kumar R, Khanal B et al (2011) Persistence of Leishmania donovani antibodies in past visceral leishmaniasis cases in India. Clin Vaccine Immunol 18(2):346–348CrossRefPubMedCentralPubMed Gidwani K, Picado A, Ostyn B, Singh SP, Kumar R, Khanal B et al (2011) Persistence of Leishmania donovani antibodies in past visceral leishmaniasis cases in India. Clin Vaccine Immunol 18(2):346–348CrossRefPubMedCentralPubMed
22.
go back to reference Hailu A (1990) Pre- and post-treatment antibody levels in visceral leishmaniasis. Trans R Soc Trop Med Hyg 84(5):673–675CrossRefPubMed Hailu A (1990) Pre- and post-treatment antibody levels in visceral leishmaniasis. Trans R Soc Trop Med Hyg 84(5):673–675CrossRefPubMed
23.
go back to reference Rahman R, Bangali M, Kabir H, Naher FB, Mahboob S (2008) Kala-azar situation in Bangladesh. In: Hossain M (ed) National guideline and training module for Kala-azar elimination in Bangladesh, 1st edition. Ministry of Health and Family Welfare, Government of the People’s Republic of Bangladesh, p 35 Rahman R, Bangali M, Kabir H, Naher FB, Mahboob S (2008) Kala-azar situation in Bangladesh. In: Hossain M (ed) National guideline and training module for Kala-azar elimination in Bangladesh, 1st edition. Ministry of Health and Family Welfare, Government of the People’s Republic of Bangladesh, p 35
24.
go back to reference Mondal D, Alvar J, Hasnain MG, Hossain MS, Ghosh D, Huda MM et al (2014) Efficacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh: a feasibility study. Lancet Glob Health 2(1):e51–e57CrossRefPubMed Mondal D, Alvar J, Hasnain MG, Hossain MS, Ghosh D, Huda MM et al (2014) Efficacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh: a feasibility study. Lancet Glob Health 2(1):e51–e57CrossRefPubMed
25.
go back to reference Bhatia A, Daifalla NS, Jen S, Badaro R, Reed SG, Skeiky YA (1999) Cloning, characterization and serological evaluation of K9 and K26: two related hydrophilic antigens of Leishmania chagasi. Mol Biochem Parasitol 102(2):249–261CrossRefPubMed Bhatia A, Daifalla NS, Jen S, Badaro R, Reed SG, Skeiky YA (1999) Cloning, characterization and serological evaluation of K9 and K26: two related hydrophilic antigens of Leishmania chagasi. Mol Biochem Parasitol 102(2):249–261CrossRefPubMed
26.
go back to reference Goto Y, Coler RN, Guderian J, Mohamath R, Reed SG (2006) Cloning, characterization, and serodiagnostic evaluation of Leishmania infantum tandem repeat proteins. Infect Immun 74(7):3939–3945CrossRefPubMedCentralPubMed Goto Y, Coler RN, Guderian J, Mohamath R, Reed SG (2006) Cloning, characterization, and serodiagnostic evaluation of Leishmania infantum tandem repeat proteins. Infect Immun 74(7):3939–3945CrossRefPubMedCentralPubMed
27.
go back to reference Boelaert M, El-Safi S, Hailu A, Mukhtar M, Rijal S, Sundar S et al (2012) Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent. Trans R Soc Trop Med Hyg 102:32–40CrossRef Boelaert M, El-Safi S, Hailu A, Mukhtar M, Rijal S, Sundar S et al (2012) Diagnostic tests for kala-azar: a multi-centre study of the freeze-dried DAT, rK39 strip test and KAtex in East Africa and the Indian subcontinent. Trans R Soc Trop Med Hyg 102:32–40CrossRef
28.
go back to reference Riera C, Fisa R, Lopez P, Ribera E, Carrió J, Falcó V et al (2004) Evaluation of a latex agglutination test (KAtex) for detection of Leishmania antigen in urine of patients with HIV-Leishmania coinfection: value in diagnosis and post-treatment follow-up. Eur J Clin Microbiol Infect Dis 23:899–904PubMed Riera C, Fisa R, Lopez P, Ribera E, Carrió J, Falcó V et al (2004) Evaluation of a latex agglutination test (KAtex) for detection of Leishmania antigen in urine of patients with HIV-Leishmania coinfection: value in diagnosis and post-treatment follow-up. Eur J Clin Microbiol Infect Dis 23:899–904PubMed
29.
go back to reference Salam MA, Khan MGM, Mondal D (2011) Urine antigen detection by latex agglutination test for diagnosis and assessment of initial cure of visceral leishmaniasis. Trans R Soc Trop Med Hyg 105(5):269–272CrossRefPubMed Salam MA, Khan MGM, Mondal D (2011) Urine antigen detection by latex agglutination test for diagnosis and assessment of initial cure of visceral leishmaniasis. Trans R Soc Trop Med Hyg 105(5):269–272CrossRefPubMed
30.
go back to reference Chaouch M, Mhadhbi M, Adams ER, Schoone GJ, Limam S, Gharbi Z et al (2013) Development and evaluation of a loop-mediated isothermal amplification assay for rapid detection of Leishmania infantum in canine leishmaniasis based on cysteine protease B genes. Vet Parasitol 198(1–2):78–84CrossRefPubMed Chaouch M, Mhadhbi M, Adams ER, Schoone GJ, Limam S, Gharbi Z et al (2013) Development and evaluation of a loop-mediated isothermal amplification assay for rapid detection of Leishmania infantum in canine leishmaniasis based on cysteine protease B genes. Vet Parasitol 198(1–2):78–84CrossRefPubMed
31.
go back to reference Pourabbas B, Ghadimi Moghadam A, Pouladfar G, Rezaee Z, Alborzi A (2013) Quantification of Leishmania infantum kinetoplast DNA for monitoring the response to meglumine antimoniate therapy in visceral leishmaniasis. Am J Trop Med Hyg 88(5):868–871CrossRefPubMedCentralPubMed Pourabbas B, Ghadimi Moghadam A, Pouladfar G, Rezaee Z, Alborzi A (2013) Quantification of Leishmania infantum kinetoplast DNA for monitoring the response to meglumine antimoniate therapy in visceral leishmaniasis. Am J Trop Med Hyg 88(5):868–871CrossRefPubMedCentralPubMed
32.
go back to reference Patil RR, Muliyil JP, Nandy A, Addy A, Maji AK, Chatterjee P (2012) Dynamics of the antibodies in cohorts of cured cases of visceral leishmaniasis: its implication on the validity of serological test, value in prognosis and in post therapeutic assessment. Hum Vaccin Immunother 8(6):725–730CrossRefPubMed Patil RR, Muliyil JP, Nandy A, Addy A, Maji AK, Chatterjee P (2012) Dynamics of the antibodies in cohorts of cured cases of visceral leishmaniasis: its implication on the validity of serological test, value in prognosis and in post therapeutic assessment. Hum Vaccin Immunother 8(6):725–730CrossRefPubMed
33.
go back to reference Sundar S, Chatterjee M (2006) Visceral leishmaniasis—current therapeutic modalities. Indian J Med Res 123(3):345–352PubMed Sundar S, Chatterjee M (2006) Visceral leishmaniasis—current therapeutic modalities. Indian J Med Res 123(3):345–352PubMed
Metadata
Title
Specific antibody responses as indicators of treatment efficacy for visceral leishmaniasis
Authors
A. C. Vallur
A. Hailu
D. Mondal
C. Reinhart
H. Wondimu
Y. Tutterrow
H. W. Ghalib
S. G. Reed
M. S. Duthie
Publication date
01-04-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 4/2015
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-014-2282-9

Other articles of this Issue 4/2015

European Journal of Clinical Microbiology & Infectious Diseases 4/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.