LOCALIZED CUTANEOUS LEISHMANIASIS DUE TO LEISHMANIA DONOVANI AND LEISHMANIA TROPICA: PRELIMINARY FINDINGS OF THE STUDY OF 161 NEW CASES FROM A NEW ENDEMIC FOCUS IN HIMACHAL PRADESH, INDIA

Abstract An endemic focus of cutaneous leishmaniasis (CL) is located in the Sutlej River Valley in Himachal Pradesh (India) in the north-western Himalaya where CL co-exists with visceral leishmaniasis (VL). In areas of the Indian subcontinent such as Rajasthan, cutaneous leishmaniasis is transmitted by Phlebotomus papatasi (Scopoli) and Phlebotomus salehi. In Himachal Pradesh, Phlebotomus longiductus (Parrot) is suspected to be the vector for CL. In the current study, sand flies were collected and tested for Leishmania infection and to confirm the vector species causing CL. Sand flies were collected during April and September of 2017–2019 from CL endemic villages of Rampur (Shimla), Nirmand (Kullu) and Nichar (Kinnaur) districts of Himachal Pradesh. The sand flies were identified as Phlebotomus (adlerius) longiductus (Parrot) and Phlebotomus (larrousisus) major (Annandale). The density of P. longiductus was found highest. The elevation of villages ranged from 947 m to 2,130 m and were far from the presence of subsoil water. Field collected sand flies tested positive (7.69%) for Leishmania donovani by PCR-RFLP. The L. donovani sequences detected from P. longiductus were 97% similar to L. donovani sequences reported from the cases of CL in Himachal Pradesh.The Leishmania positive sand flies were morphologically identified as Phlebotomus adlerious longiductus providing one step further evidence towards the vector status of CL in Himachal Pradesh. The findings of the study are of epidemiological significance for strategic planning of vector control for leishmaniasis in India.

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Mechanisms of acquired immunity in leishmaniasis

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1984.0111 ◽

1984 ◽

Vol 307 (1131) ◽

pp. 87-98 ◽

Cited By ~ 23

Keyword(s):

T Cells ◽

Cutaneous Leishmaniasis ◽

Leishmania Donovani ◽

Inbred Mouse ◽

Delayed Type Hypersensitivity ◽

Acquired Immunity ◽

Cell Mediated Immunity ◽

Leishmania Tropica ◽

Specific Suppression ◽

Heat Stable

Self-curing cutaneous leishmaniasis depends on T cell-mediated immune activation of infected macrophages. Failure of immune control in inbred mouse models of metastasizing mucocutaneous and visceralizing forms of the disease involves, respectively, insusceptibility of the parasite and the generation of T cells that suppress a potentially curative response. Prophylactic immunization in man has so far been restricted to cutaneous leishmaniasis and based on inducing infection under controlled conditions with virulent Leishmania tropica major promastigotes. The feasibility of immunization against visceral leishmaniasis merits reconsideration. BALB/c mice are genetically vulnerable to L. tropica major , which produces a fatal visceralizing type of disease involving specific suppression of cell-mediated immunity. Potent and lasting protection can be induced by repeated intravenous immunization with irradiated promastigotes. The efficacy of this ‘vaccine’ is relatively heat-stable (1 h at 56 °C). Immunity is not attributable to antibody but to the generation of Lyt-1 + 2 - T cells which, although possessing helper and macrophage-activating functions, do not express classical delayed-type hypersensitivity. The immunological features of this system and its relevance to the possibility of protection against human Leishmania donovani infection are considered.

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Phylogenetic position of Leishmania tropica isolates from an old endemic focus in south‐eastern Iran; relying on atypical cutaneous leishmaniasis

Transboundary and Emerging Diseases ◽

10.1111/tbed.13818 ◽

2020 ◽

Author(s):

Hajar Ziaei Hezarjaribi ◽

Mehdi Karamian ◽

Tahmineh Geran Orimi ◽

Abdol Sattar Pagheh ◽

Seyed Naser Emadi ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Phylogenetic Position ◽

Leishmania Tropica ◽

South Eastern ◽

Endemic Focus ◽

Eastern Iran

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Leptomonas seymouri Co-infection in Cutaneous Leishmaniasis Cases Caused by Leishmania donovani From Himachal Pradesh, India

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.00345 ◽

2020 ◽

Vol 10 ◽

Author(s):

Lovlesh Thakur ◽

Hemant Ritturaj Kushwaha ◽

Ajeet Negi ◽

Aklank Jain ◽

Manju Jain

Keyword(s):

Cutaneous Leishmaniasis ◽

Leishmania Donovani ◽

Himachal Pradesh

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An Insight Into Systemic Immune Response in Leishmania donovani Mediated Atypical Cutaneous Leishmaniasis in the New Endemic State of Himachal Pradesh, India

Frontiers in Immunology ◽

10.3389/fimmu.2021.765684 ◽

2022 ◽

Vol 12 ◽

Author(s):

Lovlesh Thakur ◽

Priyanka Madaan ◽

Aklank Jain ◽

Vinay Shankar ◽

Ajeet Negi ◽

...

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Expression Pattern ◽

Leishmania Donovani ◽

Parasite Species ◽

Himachal Pradesh ◽

Systemic Immune Response ◽

Immune Correlates ◽

Ifn Γ ◽

Endemic State

Leishmaniasis continues to afflict known and newer endemic sites despite global efforts towards its control and elimination. In this regard, the emergence of newer endemic sites with unusual disease formats is recognized wherein Leishmania donovani complex classically known to cause visceral disease is demonstrated to cause cutaneous manifestation. In this context, atypical cutaneous leishmaniasis (CL) cases caused by L. donovani genetic variants from the newer endemic state of Himachal Pradesh (HP) in India are beginning to be understood in terms of parasite determinants. The atypical CL manifestation further needs to be explored to define host immune correlates with a possible role in driving the unusual disease progression. In the given study, we performed comprehensive systemic-immune profiling of the atypical CL patients from the study area in HP, India, in comparison with the classical visceral leishmaniasis (VL) patients from the northeast region of India. The systemic immune response was studied using ELISA-based assessment of Th1, Th2, Th17, Treg, and Th22 specific plasma cytokine expression pattern and parasite-specific total serum IgG/IgG subclasses. The specified immune correlates are known to exhibit heterogeneous association with the different infecting parasite species, infection load, and co-lateral host immunopathology in classical CL and VL. In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-γ/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-γ/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response. Overall, the study highlights new knowledge on host immune correlates in terms of cytokine expression pattern and IgG subclasses that underline atypical disease manifestation such that L. donovani, a generally visceralizing parasite species cause skin localized cutaneous lesions.

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In VitroandIn VivoEfficacy of Novel Flavonoid Dimers against Cutaneous Leishmaniasis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02425-13 ◽

2014 ◽

Vol 58 (6) ◽

pp. 3379-3388 ◽

Cited By ~ 16

Author(s):

Iris L. K. Wong ◽

Kin-Fai Chan ◽

Yun-Fu Chen ◽

Zhao-Rong Lun ◽

Tak Hang Chan ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Leishmania Donovani ◽

Leishmania Major ◽

Leishmania Braziliensis ◽

Leishmania Tropica ◽

Content Type ◽

New Class ◽

Limited Efficacy ◽

Intralesional Administration ◽

Subcutaneous Inoculation

ABSTRACTTreatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. We previously reported that synthetic flavonoid dimers have potent antipromastigote and antiamastigote activity againstLeishmania donovani, the causative agent of visceral leishmaniasis. Here, we further investigate their leishmanicidal activities against cutaneousLeishmaniaspecies. One of the flavonoid dimers (compound 39) has marked antipromastigote (50% inhibitory concentrations [IC50s], 0.19 to 0.69 μM) and antiamastigote (IC50s, 0.17 to 2.2 μM) activities toward different species ofLeishmaniathat cause cutaneous leishmaniasis, includingLeishmania amazonensis,Leishmania braziliensis,Leishmania tropica, andLeishmania major. Compound 39 is not toxic to peritoneal elicited macrophages, with IC50values higher than 88 μM. In the mouse model of cutaneous leishmaniasis induced by subcutaneous inoculation ofL. amazonensisin mouse footpads, intralesional administration of 2.5 mg/kg of body weight of compound 39.HCl can reduce footpad thickness by 36%, compared with that of controls values. The amastigote load in the lesions was reduced 20-fold. The present study suggests that flavonoid dimer 39 represents a new class of safe and effective leishmanicidal agent against visceral and cutaneous leishmaniasis.

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Leishmanicidal Activity of Plant Extracts from Sefrou, a Moroccan Focus of Leishmaniasis, against Various Leishmania Parasites in the Promastigote Stage

Phytothérapie ◽

10.3166/phyto-2018-0085 ◽

2018 ◽

Vol 17 (2) ◽

pp. 83-89 ◽

Cited By ~ 1

Author(s):

I. Zeouk ◽

A. Et-Touys ◽

M. Balouiri ◽

H. Fellah ◽

A. El Ouali Lalami ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Plant Extracts ◽

Leishmania Infantum ◽

Leishmania Major ◽

Local Population ◽

Public Health Problem ◽

World Health ◽

Total Phenolic ◽

Leishmania Tropica ◽

Cistus Salviifolius

According to the World Health Organization, leishmaniasis remains a major worldwide public health problem. The province of Sefrou located in the center of Morocco is a focus of cutaneous leishmaniasis. The present study aims at evaluating the antileishmanial potential of Berberis sp.,Crataegus oxyacantha, Cistus salviifolius, Ephedra altissima and Lavandula dentatafrequently used by the local population. Methanolic extracts were tested against the promastigote form ofLeishmania tropica, Leishmania majorandLeishmania infantumusing tetrazolium-based colorimetric (MTT) assay. The total phenol and flavonoids content of all extracts were determined using the Folin–Ciocalteu reagent, aluminum chloride, and potassium acetate solutions respectively. The plant extracts exhibited antileishmanial activity with variability depending on the tested strain and the plant species compared to Glucantime® used as control (IC50 (the half maximal inhibitory concentration) > 1,000 μg/mL). The best inhibition was observed with Berberis sp., againstLeishmania major(IC50 = 394.40 ± 3.02 μg/ml), andEphedra altissima(reported for the first time) againstLeishmania infantum(IC50 = 490.84 ± 3.15 μg/mL).Leishmania tropicahas shown the same sensitivity behavior toward the five extracts (in average IC50 = 540 ± 11.20 μg/mL). The total phenolic content was higher forCrataegus oxyacanthaandCistus salviifolius(140.67 ± 3.17 μg eq Gallic Acid (GA)/ mg of Extract (E) and 133.83 ± 9.03 μg eq GA/mg of E respectively), while flavonoid was higher forCistus salviifoliusandLavandula dentata(57.92 ± 2.46 μg eq Quercetin (Que)/ mg of Extract (E) and 41.53 ± 1.74 μg eq Que/mg of E). All the tested extracts present some promising aspects that may cure cutaneous leishmaniasis in the center of Morocco; further bioguided assays are needed to isolate the fractions and the bioactive molecule.

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Complicated cutaneous leishmaniasis caused by an imported case of Leishmania tropica in Japan: a case report

Tropical Medicine and Health ◽

10.1186/s41182-021-00312-4 ◽

2021 ◽

Vol 49 (1) ◽

Author(s):

Hiroyuki Kitano ◽

Chizu Sanjoba ◽

Yasuyuki Goto ◽

Kazumasa Iwamoto ◽

Hiroki Kitagawa ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Skin Lesions ◽

Leishmania Tropica ◽

Case Presentation ◽

Imported Case ◽

Imported Cases ◽

History Of ◽

Hematoxylin And Eosin ◽

Polymerase Chain ◽

Positive Results

Abstract Background Leishmaniasis is not endemic in Japan, and imported cases are rare. However, there are increasing concerns regarding imported cases of cutaneous leishmaniasis from endemic countries to Japan. This report describes a case of imported cutaneous leishmaniasis that was diagnosed and treated in Japan. Case presentation A 53-year-old Pakistani man presented with skin lesions on both malleoli of his right ankle and the dorsum of the left foot. The skin lesions manifested as erythematous nodules surrounding an ulcer in the center of the lesion. The lesions of the malleoli of his right ankle each measured 3 × 3 cm, and the lesion on the top of his left foot measured 5 × 4 cm. He had been living and working in Japan but had a history of a visit to Pakistan for about 2 months in 2018. The skin lesions were biopsied. Giemsa and hematoxylin and eosin staining of biopsy samples showed amastigotes of Leishmania in macrophages, and the presence of Leishmania was confirmed by skin tissue culture. Polymerase chain reaction using biopsy specimens identified Leishmania parasites, and DNA sequence analysis revealed that the species was Leishmania tropica. The patient was treated with intravenous liposomal amphotericin B for 6 days. The erythema disappeared, and the erythematous nodules resolved within 3 weeks. Conclusion This is the first report of imported cutaneous leishmaniasis caused by L. tropica from Pakistan, and it is interesting that all three testing modalities showed positive results in this case.

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