Browsing by Author "Oghumu, S."

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In situ immune response to cutaneous leishmaniasis in Sri Lanka
(Sri Lanka Medical Association, 2017) Manamperi, N.H.; Oghumu, S.; Pathirana, N.; de Silva, M.V.C.; Abeyewickreme, W.; Satoskar, A.R.; Karunaweera, N.D.
INTRODUCTION & OBJECTIVES: Cutaneous leishmaniasis (CL) in Sri Lanka is caused by Leishmania donovani-MON 37, known to cause visceral leishmaniasis elsewhere. Localized immune response may play a role in disease outcome with T helper (Th) 1 response favouring lesion healing and Th2 response leading to disease progression in animal models. This study describes the localized host immune response to CL in Sri Lanka. METHOD: Skin punch biopsies from 58 patients with parasitologically confirmed CL and 25 healthy controls were quantified for cytokine gene expression of Th1 cytokines interferon (IFN)-γ, interleukin (IL)-12A and tumour necrosis factor (TNF)-α and Th2 cytokines, IL-4 and IL-10 by real-time RT-PCR. Relative copy numbers were calculated using the 2-ΔΔCt method. Non-parametric Mann-Whitney U test and the Spearman’s correlation test were used for statistical analysis. RESULTS: Study group consisted of 37 (63.8%) males and 21 (36.2%) females with a mean age of 35.0 years (SD=12.1, range=18-66), mean lesion duration of 6.75 ±9.1 months (range: 1-48) and a mean size of 176.59±185.76 mm2 (range: 12.6–908.3 mm2). Significant up regulation of IFN-γ (p<0.001) and down regulation of IL-4 (p<0.001) were seen in patients compared to healthy controls. Time taken for lesions to heal correlated significantly with in situ expression of IL-4 (Spearman’s r=0.321, p=0.034). CONCLUSION: Immune response to L. donovani induced CL in Sri Lanka tends to follow the typical Th1/Th2 convention with a Th2 biased milieu favouring poor responsiveness to antimony and delayed lesion healing.
In situ immunopathological changes in cutaneous leishmaniasis due to Leishmania donovani
(Oxford, Wiley, 2017) Manamperi, N.H.; Oghumu, S.; Pathirana, N.; de Silva, V.C.; Abeyewickreme, W.; Satoskar, A.R.; Karunaweera, N.D.
INTRODUCTION: Cutaneous leishmaniasis in Sri Lanka is a newly established parasitic disease caused by the usually visceralizing Leishmania donovani. Skin lesions manifest as non-itchy, non-tender papules, nodules or ulcers. In situ cytokine expression provides clues for immunopathogenesis of this localized form of disease. METHODS: Skin biopsies from 58 patients were analyzed for histological appearance and in situ cytokine expression of T- helper 1 (Th1) and T- helper 2 (Th2) cytokines, namely interferon (IFN)-γ, interleukin (IL)-12A, tumor necrosis factor (TNF)-α, IL-4 and IL-10 by real-time RT- PCR. RESULTS: Significant up regulation of the Th1 cytokine IFN-γ and down regulation of the Th2 cytokine IL-4 was seen in patients compared to healthy controls. Significantly elevated tissue expression of IFN-γ and TNF-α was seen in lesions that presented later than 6 months from the time of onset, while IL-4 expression was more prominent in lesions that responded poorly to antimony therapy. CONCLUSION: A prominent Th1 response appears to support resolving of lesions, whereas a Th2 biased milieu tends to favor poor responsiveness to antimony and delayed lesion healing in L. donovani infections in Sri Lanka. This article is protected by copyright. All rights reserved.
Pathogenesis of Leishmania donovani induced cutaneous leishmaniasis: role of Tumor Necrosis Factor α
(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2016) Manamperi, N.H.; Oghumu, S.; Pathirana, K.P.N.; Munidasa, U.A.D.D.; Somaratne, K.K.V.N.; Rathnayake, R.M.D.I.; Thilakaratne, S.M.; de Silva, M.V.C.; Pathmeswaran, A.; Abeyewickreme, W.; Satoskar, A.R.; Karunaweera, N.D.
BACKGROUND: Cutaneous leishmaniasis (CL) in Sri Lanka is caused by the usually visceralizing Leishmania donovani. Host immune response plays a key role in the clinical presentation of leishmaniasis. Role of cytokines in pathogenesis of local lesions has not been studied. OBJECTIVE: To describe tissue cytokine expression with lesion progression with time in CL due to Leishmania donovani. METHODS: Skin biopsies from fifty eight patients with parasitologically or histopathologically confirmed CL and 30 healthy controls were analyzed for local tissue expression of Interleukin (IL)-12A, IL-4, IL-10, Interferon-gamma (IFNg) and Tumor Necrosis Factor-alpha (TNF-α). Cytokine mRNA was quantified by real-time RT- PCR using SYBR green. Relative copy numbers were calculated for each gene by 2-ΔΔCt method using β-actin as the reference gene and healthy controls as the calibrator. Spearman correlation was used to determine the correlation between cytokines and duration of active skin lesions. RESULTS: The study group consisted of 37 males (63.8%) and 21 females (36.2%) with a mean age of 35 (SD=12.05) years which ranged between 18-66 years. Mean duration of lesions was 6.8 (SD=9.10) months with a range of 1-48 months. The Spearman correlation coefficient for relative copy numbers and lesion duration was 0.220, 0.077, 0.073, 0.235 and 0.295 for IL-12A, IL-4, IL-10, IFNg and TNF-α respectively. There was a significant positive correlation between expression of TNF-α and lesion duration (p= 0.024). CONCLUSIONS: Localized expression of TNF-α increases with time in CL due to L. donovani in Sri Lanka, which indicates development of a pro-inflammatory immune response at the site of infection as the disease progresses.