Unresponsiveness to meglumine antimoniate in anthroponotic cutaneous leishmaniasis field isolates: analysis of resistance biomarkers by gene expression profiling

Oliaee, Razieh Tavakoli; Sharifi, Iraj; Afgar, Ali; Kareshk, Amir Tavakoli; Asadi, Arash; Heshmatkhah, Amireh; Bamorovat, Mehdi; Jafarzadeh, Abdollah; Mohammadi, Mohammad Ali; Daneshvar, Hamid

doi:10.1111/tmi.13062

Cited by 39 publications

(36 citation statements)

References 41 publications

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“…Numerous risk determinants have contributed to the recent rise in transmission, the incidence of cases and expansion to new geographical ranges. These include environmental changes, anthropogenic modifications, population displacement, climate change, global conflict, poor standards of living and drug resistance (Aflatoonian et al, ; Bamorovat, Sharifi, Aflatoonian, et al, ; Bamorovat et al, ; Desjeux, ; Nikonahad et al, ; Oliaee et al, ). In the presence of such pre‐existing risk factors, CL has become a dynamic disease, as has been documented by several reports (Bailey et al, ; Karimkhani et al, ; WHO, ).…”

Section: Introductionmentioning

confidence: 99%

Expansion of urban cutaneous leishmaniasis into rural areas of southeastern Iran: Clinical, epidemiological and phylogenetic profiles explored using 7SL high resolution melting‐PCR analysis

Razavinasab

Sharifi

Aflatoonian

et al. 2019

Transbound Emerg Dis

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Cutaneous leishmaniasis (CL) has increased remarkably in Iran and has expanded into new areas. The present study aimed to assess the emerging CL outbreak in southeastern Iran using high resolution melting-polymerase chain reaction (HRM-PCR) and phylogenetic analysis using the 7SL RNA gene marker. A cross-sectional and analytical survey was conducted during a house-to-house census of 11,021 inhabitants in Narmashir County in southeastern Iran in 2016. The cases were detected by direct smear microscopic examination and sequencing and were characterized using the 7SL RNA gene. All age groups and sexes were equally affected. Most were single lesions (70.7%). The hands (55.2%) and face (37.9%) were the main sites of involvement.The disease was more common among illiterate persons. Sequencing and HRM-PCR revealed that Leishmania tropica (accession no. MH632168 Qale-Shahid) was the principal causative agent of anthroponotic CL (ACL) in new areas of expansion. This is the first emergence of ACL in rural areas of Narmashir County. Based on the molecular data, the causative parasite species confirmed to be L. tropica. Sequencing and phylogenetic analysis indicated that a single clone of the organism derived from a single source has spread into the affected villages. Construction of a main road, population movement and recent urbanization in the area are likely the major factors associated with the establishment of this new outbreak. This study was essential to enable the planning of effective therapeutic and prophylactic measures to control the disease. K E Y W O R D S cutaneous leishmaniasis epidemic, HRM-PCR, Iran, Leishmania tropica | 1603 RAZAVINASAB et Al.

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Section: Introductionmentioning

confidence: 99%

Expansion of urban cutaneous leishmaniasis into rural areas of southeastern Iran: Clinical, epidemiological and phylogenetic profiles explored using 7SL high resolution melting‐PCR analysis

Razavinasab

Sharifi

Aflatoonian

et al. 2019

Transbound Emerg Dis

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“…Despite extensive efforts to prepare an appropriate vaccine for the control and treatment of leishmaniasis, this disease is still threatening the lives of human beings. Antimony compounds have been used for the treatment of this disease for years, and resistance against pentavalent antimony (SbV) has significantly been increased [23]. Achievement of an effective vaccine is essential for this disease.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a new live recombinant vaccine against cutaneous leishmaniasis in BALB/c mice

et al. 2020

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Background: Leishmaniasis is a serious health problem in some parts of the world. In spite of the many known leishmaniasis control measures, the disease has continued to increase in endemic areas, and no effective vaccine has been discovered. Methods: In this study, Leishmania tarentulae was used as a living factory for the production of two LACK and KMP11 immunogenic antigens in the mice body, and safety profiles were investigated. The sequences of the KMP11 and LACK L. major antigens were synthesized in the pLEXSY-neo 2.1 plasmid and cloned into E. coli strain Top10, and after being linearized with the SwaI enzyme, they were transfected into the genome of L. tarentolae. The L. tarentolae-LACK/ KMP11/EGFP in the stationary phase with CpG ODN as an adjuvant was used for vaccination in BALB/c mice. Vaccination was performed into the left footpad. Three weeks later, the booster was injected in the same manner. To examine the effectiveness of the injected vaccine, pathogenic L. major (MRHO/IR/75/ER) was injected into the right footpad of all mice three weeks following the booster vaccination. In order to assess humoral immunity, the levels of IgG1, and IgG2a antibodies before and 6 weeks after the challenge were studied in the groups. In addition, in order to investigate cellular immunity in the groups, the study measured IFN-γ, IL-5, TNF-α, IL-6 and IL-17 cytokines before, 3 weeks and 8 weeks after the challenge, and also the parasite load in the lymph node with real-time PCR. Results: The lowest level of the parasitic load was observed in the G1 group (mice vaccinated with L. tarentolae-LACK/KMP11/EGFP with CpG) in comparison with other groups (L. tarentolae-LACK/KMP11/EGFP +non-CpG (G2); L. tarentolae-EGFP + CpG (G3, control); L. tarentolae-EGFP + non-CpG (G4, control); and mice injected with PBS (G5, control). Moreover, the evaluation of immune response showed a delayed-type hypersensitivity towards Th1. Conclusions: According to the results of this study, the live recombinant vaccine of L. tarentolae-LACK/KMP11/EGFP with the CpG adjuvant reduced the parasitic load and footpad induration in infected mice. The long-term effects of this vaccine can be evaluated in volunteers as a clinical trial in future planning.

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“…Despite the high number of people affected, leishmaniasis control programs present difficulties not only with the diagnosis of cases and the control of vectors to reduce transmission but also with the treatment, given that the therapeutic response with the available drugs is becoming poorer due to incomplete treatments or the development of resistance in the parasites (Oliaee et al, 2018). Unfortunately, the confirmation of a definitive cure is complicated by the possibility of relapses after an initial cure, making necessary long follow-up periods (up to 6 or 12 months).…”

Section: Introductionmentioning

confidence: 99%

Label-free quantitative proteomic analysis reveals potential biomarkers for early healing in cutaneous leishmaniasis

Montoya

López

Vélez

et al. 2019

PeerJ

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BackgroundLeishmaniasis is a parasitic disease caused by more than 20 species of the Leishmania genus. The disease is globally distributed and is endemic in 97 countries and three territories in the tropical and subtropical regions. The efficacy of the current treatments is becoming increasingly low either due to incomplete treatment or resistant parasites. Failure of treatment is frequent, and therefore, the search for early biomarkers of therapeutic response in cutaneous leishmaniasis (CL) is urgently needed.ObjectiveThe aim of this study was to compare the proteomic profiles in patients with CL before and after 7 days of treatment and identify early biomarkers of curative response.MethodsFour patients with a parasitological diagnosis of leishmaniasis with confirmation of species by PCR-RFLP were recruited. All patients had a single lesion, and a protein from the middle of the ulcer was quantified by liquid chromatography and mass spectrometry.ResultsA total of 12 proteins showed differential expression in the comparative LC-electrospray ionization MS/MS (LC-ESI-MS/MS) triplicate analysis. Seven of them were up-regulated and five of them were down-regulated. Calcium binding proteins A2, A8, and A9 and hemoglobin subunits alpha-2 and delta showed high correlation with epidermis development and immune response.ConclusionWe identified changes in the profiles of proteins that had a positive therapeutic response to the treatment. The proteins identified with differential expression are related to the reduction of inflammation and increased tissue repair. These proteins can be useful as biomarkers for early monitoring of therapeutic response in CL.

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Unresponsiveness to meglumine antimoniate in anthroponotic cutaneous leishmaniasis field isolates: analysis of resistance biomarkers by gene expression profiling

Abstract: In cases of inconclusive outcomes of resistance tests in clinical isolates, expression analysis of a set of influential genes can be beneficial to identify distinctive biomarkers between antimony-unresponsive and responsive parasites.

Cited by 39 publications

References 41 publications

Expansion of urban cutaneous leishmaniasis into rural areas of southeastern Iran: Clinical, epidemiological and phylogenetic profiles explored using 7SL high resolution melting‐PCR analysis

Expansion of urban cutaneous leishmaniasis into rural areas of southeastern Iran: Clinical, epidemiological and phylogenetic profiles explored using 7SL high resolution melting‐PCR analysis

Evaluation of a new live recombinant vaccine against cutaneous leishmaniasis in BALB/c mice

Label-free quantitative proteomic analysis reveals potential biomarkers for early healing in cutaneous leishmaniasis

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