Identification of Clinical Immunological Determinants in Asymptomatic VL and Post Kala-azar Dermal Leishmaniasis Patients
AbstractBackground: Visceral Leishmaniasis (VL) caused by protozoa belonging to the genus Leishmania, usually have anthroponotic mode of transmission and is issue of great public health importance in Indian subcontinent. Asymptomatic cases of VL and PKDL are subject of keen interest to find their role in the transmission of VL in epidemic areas. We evaluated the immunological cytokine determinants expressed in most clinical suspects of asymptomatic VL and PKDL (IL-10, IFN-γ, and TNF-α). Methods: Eighty-four participants were included at RMRIMS, Patna, India in 2016-17 out of which 64 asymptomatic individual positive for rK-39, without sign and symptoms of VL; 15 PKDL patient’s with past history of VL and 5 endemic healthy subjects were recruited from VL endemic areas. DAT and quantitative assessment of plasma cytokines was determined from the blood samples collected in a plain and sodium-EDTA vacutainer respectively from the subjects. Results: The mean level of IL-10 in DATposLOW of asymptomatic VL and PKDL was significantly higher than endemic healthy (P<0.05). The cytokine polarization index (IFN-γ versus IL-10) was significantly low in PKDL cases compared with asymptomatic VL cases in DATposLOW titre (P<0.05). This index was low again but statistically not significant in PKDL than in asymptomatic VL when TNF-α was considered against IL-10. The ratio of IFN-γ: IL-10 and TNF-α: IL-10 was observed decreased both in asymptomatic VL and PKDL cases than in healthy from endemic areas. Conclusion: Collectively we surmise from our data that asymptomatic VL can also play an important role like PKDL in transmission of VL.
Bates PA. Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies. International journal for parasitology. 2007;37(10):1097-106.
WALTERS LL. Leishmania differentiation in natural and unnatural sand fly hosts. Journal of Eukaryotic Microbiology. 1993;40(2):196-206.
Bora D. Epidemiology of visceral leishmaniasis in India. The National medical journal of India. 1999;12(2):62-8.
Desjeux P. Leishmaniasis: current situation and new perspectives. Comparative immunology, microbiology and infectious diseases. 2004;27(5):305-18.
Zijlstra E, Musa A, Khalil E, El Hassan I, El-Hassan A. Post-kala-azar dermal leishmaniasis. The Lancet infectious diseases. 2003;3(2):87-98.
Singh S, Kumari V, Singh N. Predicting kala-azar disease manifestations in asymptomatic patients with latent Leishmania donovani infection by detection of antibody against recombinant K39 antigen. Clinical and diagnostic laboratory immunology. 2002;9(3):568-72.
Bimal S, Das V, Sinha P, Gupta A, Verma N, Ranjan A, et al. Usefulness of the direct agglutination test in the early detection of subclinical Leishmania donovani infection: a community-based study. Annals of Tropical Medicine & Parasitology. 2005;99(8):743-9.
Schaefer K, Kurtzhals J, Gachihi G, Muller A, Kager P. A prospective sero-epidemiological study of visceral leishmaniasis in Baringo District, Rift Valley Province, Kenya. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1995;89(5):471-5.
Schallig H, Schoone G, Kroon C, Hailu A, Chappuis F, Veeken H. Development and application of'simple'diagnostic tools for visceral leishmaniasis. Medical microbiology and immunology. 2001;190(1):69-71.
Verma N, Singh D, Pandey K, Das VNR, Lal CS, Verma RB, et al. Comparative evaluation of PCR and imprint smear microscopy analyses of skin biopsy specimens in diagnosis of macular, Papular, and mixed Papulo-nodular lesions of post-Kala-Azar dermal Leishmaniasis. Journal of clinical microbiology. 2013;51(12):4217-9.
Allain DS, Kagan IG. A direct agglutination test for leishmaniasis. The American journal of tropical medicine and hygiene. 1975;24(2):232-6.
Harith A, Kolk A, Kager P, Leeuwenburg J, Muigai R, Kiugu S, et al. A simple and economical direct agglutination test for serodiagnosis and sero-epidemiological studies of visceral leishmaniasis. Transactions of the royal society of tropical medicine and hygiene. 1986;80(4):583-6.
El Safi S, Evans DA. A comparison of the direct agglutination test and enzyme-linked immunosorbent assay in the sero-diagnosis of leishmaniasis in the Sudan. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1989;83(3):334-7.
Verma N, Bimal S, Das VNR, Pandey K, Singh D, Lal CS, et al. Clinicopathological and immunological changes in Indian post kala-azar dermal leishmaniasis (PKDL) cases in relation to treatment: A retrospective study. BioMed research international. 2015;2015.
Meredith S, Kroon N, Sondorp E, Seaman J, Goris M, Van Ingen C, et al. Leish-KIT, a stable direct agglutination test based on freeze-dried antigen for serodiagnosis of visceral leishmaniasis. Journal of Clinical Microbiology. 1995;33(7):1742-5.
Sundar S, Singh R, Maurya R, Kumar B, Chhabra A, Singh V, et al. Serological diagnosis of Indian visceral leishmaniasis: direct agglutination test versus rK39 strip test. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2006;100(6):533-7.
Sundar S, Reed SG, Singh VP, Kumar PC, Murray HW. Rapid accurate field diagnosis of Indian visceral leishmaniasis. The Lancet. 1998;351(9102):563-5.
Bhatia A, Daifalla NS, Jen S, Badaro R, Reed SG, Skeiky YA. Cloning, characterization and serological evaluation of K9 and K26: two related hydrophilic antigens of Leishmania chagasi. Molecular and biochemical parasitology. 1999;102(2):249-61.
Singh S, Sivakumar R. Polypeptides for the diagnosis and therapy of Leishamaniasis. Google Patents; 2010.
Attar ZJ, Chance ML, el-Safi S, Carney J, Azazy A, El-Hadi M, et al. Latex agglutination test for the detection of urinary antigens in visceral leishmaniasis. Acta tropica. 2001;78(1):11-6.
Sarkari B, Chance M, Hommel M. Antigenuria in visceral leishmaniasis: detection and partial characterisation of a carbohydrate antigen. Acta tropica. 2002;82(3):339-48.
Ribeiro-de-Jesus A, Almeida RPd, Lessa H, Bacellar O, Carvalho E. Cytokine profile and pathology in human leishmaniasis. Brazilian journal of medical and biological research. 1998;31(1):143-8.
Costa-Pereira C, Moreira ML, Soares RP, Marteleto BH, Ribeiro VM, França-Dias MH, et al. One-year timeline kinetics of cytokine-mediated cellular immunity in dogs vaccinated against visceral leishmaniasis. BMC veterinary research. 2015;11(1):92.
Amit A, Dikhit MR, Mishra A, Singh AK, Das V, Das P, et al. Adenosine generated by ectonucleotidases modulates the host immune system during visceral leishmaniasis. Cytokine. 2017;91:170-9.
Cenini P, Berhe N, Hailu A, McGinnes K, Frommel D. Mononuclear cell subpopulations and cytokine levels in human visceral leishmaniasis before and after chemotherapy. Journal of Infectious Diseases. 1993;168(4):986-93.
Ansari NA, Saluja S, Salotra P. Elevated levels of interferon-γ, interleukin-10, and interleukin-6 during active disease in Indian kala azar. Clinical Immunology. 2006;119(3):339-45.
El Harith A, Kolk A, Leeuwenburg J, Muigai R, Huigen E, Jelsma T, et al. Improvement of a direct agglutination test for field studies of visceral leishmaniasis. Journal of clinical microbiology. 1988;26(7):1321-5.
Amit A, Dikhit MR, Pandey RK, Singh K, Mishra R, Das VR, et al. Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients. PloS one. 2016;11(5):e0154117.
Ganguly S, Das NK, Barbhuiya JN, Chatterjee M. Post‐kala‐azar dermal leishmaniasis–an overview. International journal of dermatology. 2010;49(8):921-31.
Singh R, Kumar D, Ramesh V, Negi NS, Singh S, Salotra P. Visceral leishmaniasis, or kala azar (KA): high incidence of refractoriness to antimony is contributed by anthroponotic transmission via post-KA dermal leishmaniasis. The Journal of infectious diseases. 2006;194(3):302-6.
Barral-Netto M, Barral AMP, Brownell CE, Skeiky YA, Ellingsworth LR, Twardzik DR, et al. Transforming Growth Factor-y in Leishmanial Infection: A Parasite Escape Mechanism. 1992.