Dexamethasone: Insights into Pharmacological Aspects, Therapeutic Mechanisms, and Delivery Systems.

Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded nanoformulations that ameliorate adverse disease effects inhibiting advancements in scientific research. Various nanoparticles have been developed to selectively deliver drugs without destroying healthy cells or organs in recent years. In the present review, we have summarized some of the most attractive applications of DEX-loaded delivery systems, including liposomes, polymers, hydrogels, nanofibers, silica, calcium phosphate, and hydroxyapatite. This review provides our readers with a broad spectrum of nanomedicine approaches to deliver DEX safely.

Fifty years of struggle to control cutaneous leishmaniasis in the highest endemic county in Iran: A longitudinal observation inferred with interrupted time series model.

Negligible data are available following major social activities and environmental changes on leishmaniasis. Therefore, how interactions between these events influence cutaneous leishmaniasis (CL) risk is not well-known. This longitudinal study was undertaken to explore the impact of interventions conducted between 1971 and 2020 in Bam county, which has had the highest disease burden in Iran. Only confirmed CL cases during this period were taken into account. Data were analyzed by SPSS 22 using the X2 test to assess the significance of the difference between proportions. Moreover, we used interrupted time series (ITS) to assess the impact of three environmental events during this period. Overall, 40,164 cases of CL occurred in the past five decades. Multiple complex factors were among the leading causes that synergistically induced the emergence/re-emergence of CL outbreaks in Bam. The main factors attributed negatively to CL control were cessation of malaria spraying activity, expansion of the city spaces, and a massive earthquake creating new breeding potentials for the vectors. The highest impact on CL incidence during these years was related to the earthquake [coefficient = 17.8 (95% CI: 11.3, 22.7); p-value < 0.001]. Many factors can contribute to CL outbreaks in endemic foci. They also can cause new foci in new areas. Since humans are the single reservoir for CL in this area, early detection and effective management significantly contribute to controlling CL to reduce the disease burden. However, essential evidence gaps remain, and new tools are crucial before the disease can ultimately be controlled. Nevertheless, sustained funding and more trained task forces are essential to strengthen surveillance and case management and monitor the interventions' impact.

Voltammetric Determination of Isoniazid in the Presence of Acetaminophen Utilizing MoS2-Nanosheet-Modified Screen-Printed Electrode.

We used MoS2 nanosheets (MoS2 NSs) for surface modification of screen-printed electrode (MoS2NSs-SPE) aimed at detecting isoniazid (INZ) in the presence of acetaminophen (AC). According to analysis, an impressive catalytic performance was found for INZ and AC electro-oxidation, resulting in an appreciable peak resolution (~320 mV) for both analytes. Chronoamperometry, differential pulse voltammetry (DPV), linear sweep voltammogram (LSV), and cyclic voltammetry (CV) were employed to characterize the electrochemical behaviors of the modified electrode for the INZ detection. Under the optimal circumstances, there was a linear relationship between the peak current of oxidation and the various levels of INZ (0.035-390.0 µM), with a narrow limit of detection (10.0 nM). The applicability of the as-developed sensor was confirmed by determining the INZ and AC in tablets and urine specimens, with acceptable recoveries.

Green Synthesis of Zeolitic Imidazolate Frameworks: A Review of Their Characterization and Industrial and Medical Applications.

Metal organic frameworks (MOF) are a class of hybrid networks of supramolecular solid materials comprising a large number of inorganic and organic linkers, all bound to metal ions in a well-organized fashion. Zeolitic imidazolate frameworks (ZIFs) are a sub-group of MOFs with imidazole as an organic linker to metals; it is rich in carbon, nitrogen, and transition metals. ZIFs combine the classical zeolite characteristics of thermal and chemical stability with pore-size tunability and the rich topological diversity of MOFs. Due to the energy crisis and the existence of organic solvents that lead to environmental hazards, considerable research efforts have been devoted to devising clean and sustainable synthesis routes for ZIFs to reduce the environmental impact of their preparation. Green chemistry is the key to sustainable development, as it will lead to new solutions to existing problems. Moreover, it will present opportunities for new processes and products and, at its heart, is scientific and technological innovation. The green chemistry approach seeks to redesign the materials that make up the basis of our society and our economy, including the materials that generate, store, and transport our energy, in ways that are benign for humans and the environment and that possess intrinsic sustainability. This study covers the principles of green chemistry as used in designing strategies for synthesizing greener, less toxic ZIFs the consume less energy to produce. First, the necessity of green methods in today's society, their replacement of the usual non-green methods and their benefits are discussed; then, various methods for the green synthesis of ZIF compounds, such as hydrothermally, ionothermally, and by the electrospray technique, are considered. These methods use the least harmful and toxic substances, especially concerning organic solvents, and are also more economical. When a compound is synthesized by a green method, a question arises as to whether these compounds can replace the same compounds as synthesized by non-green methods. For example, is the thermal stability of these compounds (which is one of the most important features of ZIFs) preserved? Therefore, after studying the methods of identifying these compounds, in the last part, there is an in-depth discussion on the various applications of these green-synthesized compounds.

Chitosan: A versatile bio-platform for breast cancer theranostics.

Breast cancer is considered one of the utmost neoplastic diseases globally, with a high death rate of patients. Over the last decades, many approaches have been studied to early diagnose and treat it, such as chemotherapy, hormone therapy, immunotherapy, and MRI and biomarker tests; do not show the optimal efficacy. These existing approaches are accompanied by severe side effects, thus recognizing these challenges, a great effort has been done to find out the new remedies for breast cancer. Main finding: Nanotechnology opened a new horizon to the treatment of breast cancer. Many nanoparticulate platforms for the diagnosis of involved biomarkers and delivering antineoplastic drugs are under either clinical trials or just approved by the Food and Drug Administration (FDA). It is well known that natural phytochemicals are successfully useful to treat breast cancer because these natural compounds are safer, available, cheaper, and have less toxic effects. Chitosan is a biocompatible and biodegradable polymer. Further, it has outstanding features, like chemical functional groups that can easily modify our interest with an exceptional choice of promising applications. Abundant studies were directed to assess the chitosan derivative-based nanoformulation's abilities in delivering varieties of drugs. However, the role of chitosan in diagnostics and theranostics not be obligated. The present servey will discuss the application of chitosan as an anticancer drug carrier such as tamoxifen, doxorubicin, paclitaxel, docetaxel, etc. and also, its role as a theranostics (i.e. photo-responsive and thermo-responsive) moieties. The therapeutic and theranostic potential of chitosan in cancer is promising and it seems that to have a good potential to get to the clinic.

Photodynamic therapy for leishmaniasis: Recent advances and future trends.

Leishmaniasis has infected more than 12 million people worldwide. This neglected tropical disease, causing 20,000-30,000 deaths per year, is a global health problem. The emergence of resistant parasites and serious side effects of conventional therapies has led to the search for less toxic and non-invasive alternative treatments. Photodynamic therapy is a promising therapeutic strategy to produce reactive oxygen species for the treatment of leishmaniasis. In this regard, natural and synthetic photosensitizers such as curcumin, hypericin, 5-aminolevulinic acid, phthalocyanines, phenothiazines, porphyrins, chlorins and nanoparticles have been applied. In this review, the recent advances on using photodynamic therapy for treating Leishmania species have been reviewed.

Electrochemical Detection of Hydrazine by Carbon Paste Electrode Modified with Ferrocene Derivatives, Ionic Liquid, and CoS2-Carbon Nanotube Nanocomposite.

The electrocatalytic performance of carbon paste electrode (CPE) modified with ferrocene-derivative (ethyl2-(4-ferrocenyl[1,2,3]triazol-1-yl)acetate), ionic liquid (n-hexyl-3-methylimidazolium hexafluorophosphate), and CoS2-carbon nanotube nanocomposite (EFTA/IL/CoS2-CNT/CPE) was investigated for the electrocatalytic detection of hydrazine. CoS2-CNT nanocomposite was characterized by field emission scanning electron microscopy, X-ray powder diffraction, and transmission electron microscopy. According to the results of cyclic voltammetry, the EFTA/IL/CoS2-CNT-integrated CPE has been accompanied by greater catalytic activities for hydrazine oxidation compared to the other electrodes in phosphate buffer solution at a pH 7.0 as a result of the synergistic impact of fused ferrocene-derivative, IL, and nanocomposite. The sensor responded linearly with increasing concentration of hydrazine from 0.03 to 500.0 µM with a higher sensitivity (0.073 µA µM-1) and lower limit of detection (LOD, 0.015 µM). Furthermore, reasonable reproducibility, lengthy stability, and excellent selectivity were also attained for the proposed sensor. Finally, EFTA/IL/CoS2-CNT/CPE was applied for the detection of hydrazine in water samples, and good recoveries varied from 96.7 to 103.0%.

A long-lasting emerging epidemic of anthroponotic cutaneous leishmaniasis in southeastern Iran: population movement and peri-urban settlements as a major risk factor.

BACKGROUND: Epidemics of cutaneous leishmaniasis (CL) are occurring more frequently and spreading faster and farther than before in many areas of the world. The present study aimed to assess a long-lasting emerging epidemic (2005-2019) of 5532 cases with anthroponotic CL (ACL) in peri-urban areas of Kerman city in southeastern Iran. METHODS: This descriptive-analytical study was carried out for 15 years in Kerman province, southeastern Iran. The data were passively obtained through the health surveillance system and the Kerman Leishmaniasis Research Center. Every subject was diagnosed using direct smear microscopy. The representative causative agent was further examined by ITS1-PCR, PCR-RFLP, 7SL RNA gene sequencing and phylogenetic analyses. For each subject, a case report form designating demographic and clinical data was recorded. RESULTS: A different pattern of ACL incidence was found in peri-urban areas compared to that in the city of Kerman. The incidence rate of ACL cases has significantly increased (P < 0.001) from 2005 to 2016 in new settlements with a gradual decline after that. The overall average risk of contracting the disease was 7.6 times higher in peri-urban areas compared to Kerman city, an old endemic focus. All isolates consisting of six variants were confirmed to be Leishmania tropica. The overall pattern of the ACL infection indicates that the etiological agent of ACL is propagated and transmitted by the bite of female Phlebotomus sergenti sandflies from person to person from dissimilar clones as reflected by the complexity of the migrants' backgrounds in the province. CONCLUSIONS: The movement of populations and establishment of new settlements in peri-urban areas close to endemic areas are major risk factors for and are directly linked to CL. The underlying factors of this emerging ACL epidemic caused by L. tropica were disasters and droughts, among others. A robust commitment to a multilateral approach is crucial to make improvements in this area. This will require decisive coordinated actions through all governmental factions and non-governmental organizations. Furthermore, active and passive case detection strategies, early diagnosis, and effective treatment could help control the disease.

Evaluation of Different Attractive Traps for Capturing Sand Flies (Diptera: Psychodidae) in an Endemic Area of Leishmaniasis, Southeast of Iran.

BACKGROUND: The attraction of phlebotomine sand flies to plant and animal hosts is due to the produced chemical compounds, affecting the olfactory receptors of the insects. Therefore, novel and effective methods, such as Attractive Toxic Sugar Baits (ATSB) and Attractive Toxic Baits (ATB), are based on the effective materials that attract sand flies toward the host. The present study was designed to identify the attractive materials in plants and animals for using in ATSB and ATB. METHODS: This cross-sectional study was carried out in July 2018 on endemic areas of leishmaniasis in Iran. Different baits, including mango, nectarine, grape, banana, melon and watermelon, defibrinated blood of cattle, sheep, goat and chicken, urine of cattle, sheep, goat and ultimately, simple and complex chemicals, such as CO2, 1-octanol, lactic acid and human sweat were placed inside the traps, and the rate of the sand flies attraction to these materials was studied. Furthermore, data were analyzed using the Kruskal-Wallis test and Mann Whitney U test. RESULTS: There was a significant difference in the sand flies attraction between the traps containing watermelon, urine of cattle, and sheep, and chemicals such as CO2 and human sweat and the control trap (p< 0.05). CONCLUSION: This study showed that watermelon and CO2 are the potential candidates for using in ATSB and ATB, respectively.

Modelling and evaluating the risk of zoonotic cutaneous leishmaniasis in selected areas of Kerman Province, south of Iran.

Cutaneous leishmaniasis (CL) remains a public health problem in the world, particularly in tropical and sub-tropical countries. This study aimed to determine the hotspots of CL in Kerman Province of Iran and model their potential for the establishment of new disease foci. All documents related to studies conducted in Kerman Province on CL published between 1978 and 2017 were retrieved and categorized. Spatial distributions of the vector, reservoir and human infection of CL were mapped. MaxEnt ecological model was used to predict the environmental suitability of the vector and reservoir(s) of zoonotic cutaneous leishmaniasis (ZCL). The most hazardous sites with the potential for the establishment of new disease foci were determined for field operations. Statistics of new cases of CL was obtained from the Center for Disease Control (CDC) of the ministry of health for the period 2011-2016. A total of 6,056 cases of CL were recorded, while we found a decreasing pattern in the incidence of CL from 46.48 per 100,000 inhabitants to 22.97. The best ecological niches for Phlebotomus papatasi are located in the central, western, northwest and southwest regions of the province. Also, environmental suitability for the reservoirs was highest in the central, southern and southwestern regions. The model predicted the gerbils can be present in some foci of anthroponotic cutaneous leishmaniasis (ACL). However, this result should be confirmed through a precise field study, and if validated, plans should be made to prevent the emergence of new foci of ZCL in the risk areas.

Diversity of Phlebotomine sand flies (Diptera: Psychodidae) in mountainous and plain areas of an endemic focus of anthroponotic cutaneous leishmaniasis in Iran

Objective: To determine the diversity of sand flies in different biotopes of mountainous and plain areas of Bam County as the most infected focus of anthroponotic cutaneous leishmaniasis in southeast Iran, and synanthropic index of Phlebotomus sergenti Parrot, and Phlebotomus papatasi Scopoli as the main vectors of cutaneous leishmaniasis in Iran.Methods: Sand flies were captured once a month using sticky traps in domestic, peri-domestic, agricultural, and sylvatic biotopes in the plain and mountainous areas. Alpha diversity indices, including richness, evenness, Shannon-Wiener; beta diversity indices (Jaccard's and Sorensen's similarity indices) and synanthropic index were calculated. Results: A total of 2664 specimens of 9 sand fly species were collected from mountainous (47％) and plain (53％) areas. Species richness, species evenness, and Shannon-Wiener indices were obtained as 9, 0.637, and 1.399, respectively in the mountainous area. Phlebotomus sergenti and Phlebotomus papatasi were constant species with the synanthropic index of -18.463 and -29.412, respectively. In addition, species richness, species evenness, and Shannon-Wiener indices were 4, 0.690, and 0.956, respectively in the plain area. Phlebotomus sergenti and Phlebotomus papatasi were dominant species with the synanthropic index of +9.695 and +36.207, respectively. Similarity indices were low among different biotopes of plain and mountainous areas. Conclusions: A basic knowledge about the diversity of sand flies in various biotopes is essential to design sound control programs. Biodiversity and synanthropic indices of sand flies are different in plain and mountainous areas due to the difference in biotic and abiotic factors between the two areas.

Associated-risk determinants for anthroponotic cutaneous leishmaniasis treated with meglumine antimoniate: A cohort study in Iran.

BACKGROUND: The control of cutaneous leishmaniasis (CL) is facilitated by knowledge of factors associated with the treatment failures in endemic countries. The aim of this evaluation was to identify the potential risk determinants which might affect the significance of demographic and clinical characteristics for the patients with anthroponotic CL (ACL) and the outcome of meglumine antimoniate (MA) (Glucantime) treatment. METHODOLOGY/PRINCIPAL FINDINGS: This current was executed as a cohort spanning over a period of 5 years which centered in southeastern part of Iran. Altogether, 2,422 participants were evaluated and 1,391 eligible volunteer patients with ACL caused by Leishmania tropica were included. Overall, 1,116 (80.2%) patients received MA intraleisionally (IL), once a week for 12 weeks along with biweekly cryotherapy, while 275 (19.8%) patients received MA alone (20 mg/kg/day for 3 weeks) (intramuscular, IM). The treatment failure rate in ACL patients was 11% using IL combined with cryotherapy plus IM alone, whilst 9% and 18.5% by IL along with cryotherapy or IM alone, respectively. Multivariate logistic regression model predicted 5 major associated-risk determinants including male (odds ratio (OR) = 1.54, confidence interval (CI) = 1.079-2.22, p = 0.018), lesion on face (OR = 1.574, CI = 1.075-2.303, p = 0.02), multiple lesions (OR = 1.446, CI = 1.008-2.075, p = 0.045), poor treatment adherence (OR = 2.041, CI = 1.204-3.46, p = 0.008) and disease duration > 4 months (OR = 2.739, CI = 1.906-3.936, p≤0.001). CONCLUSIONS/SIGNIFICANCE: The present study is the original and largest cohort of ACL patients who treated with MA. A comprehensive intervention and coordinated action by the health authorities and policy-makers are crucial to make sure that patients strictly follow medical instructions. Early detection and effective therapy < 4 months following the onset of the lesion is critical for successful treatment of the patients. Since a significant number of patients are still refractory to MA, reducing man-vector exposure and development of new effective alternative drugs are essential measures against ACL due to L. tropica.

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

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.

Species Composition of Sand Flies (Diptera: Psychodidae) and Modeling the Spatial Distribution of Main Vectors of Cutaneous Leishmaniasis in Hormozgan Province, Southern Iran.

Cutaneous Leishmaniasis (CL) is one of the main neglected vector-borne diseases in the Middle East, including Iran. This study aimed to map the spatial distribution and species composition of sand flies in Hormozgan Province and to predict the best ecological niches for main CL vectors in this area. A database that included all earlier studies on sand flies in Hormozgan Province was established. Sand flies were also collected from some localities across the province. Prediction maps for main vectors were developed using MaxEnt model. A total of 27 sand fly species were reported from the study area. Phlebotomus papatasi Scopoli, Phlebotomus sergenti s.l. Parrot, Phlebotomus alexandri Sinton, Sergentomyia sintoni Pringle, Sergentomyia clydei Sinton, Sergentomyia tiberiadis Adler, and Sergentomyia baghdadis Adler (Diptera: Psychodidae) had the widest distribution range. The probability of their presence as the main vectors of CL was calculated to be 0.0003-0.9410 and 0.0031-0.8880 for P. papatasi and P. sergenti s.l., respectively. The best ecological niches for P. papatasi were found in the central south, southeast, and a narrow area in southwest, whereas central south to northern area had better niches for P. sergenti s.l. The endemic areas are in Bandar-e Jask, where transmission occurs, whereas in Bastak, the cases were imported from endemic foci of Fars province. In conclusion, proven and suspected vectors of CL and VL were recorded in this study. Due to the existence of endemic foci of CL, and favorite ecological niches for its vectors, there is potential risk of emerging CL in new areas.

Baseline Susceptibility of Filarial Vector Culex quinquefasciatus (Diptera: Culicidae) to Five Insecticides with Different Modes of Action in Southeast of Iran.

BACKGROUND: Culex quinquefasciatus (Diptera: Culicidae) is an important vector for many human diseases. The aim of this study was to evaluate the susceptibility level of larval and adult stages of Cu. quinquefasciatus to different groups of WHO recommended insecticides for vector control. METHODS: Larval stages of the Culex mosquitoes were collected from their natural habitats in Rafsanjan County at Kerman Province, southeast of Iran in 2016. Insecticide susceptibility status of adult female Cx. quinquefasciatus against DDT (4%), deltamethrin (0.05%), malathion 5%, and bendiocarb (0.1%) were determined using WHO standard insecticide susceptibility test. Additional test was carried out to determine the susceptibility status of larvae of Cx. quinquefasciatus to temephos. Bioassay data were analyzed by Probit program. RESULTS: Cx. quinquefasciatus adults showed resistance to all four groups of the tested insecticides according to the WHO criteria for resistance evaluation. The lethal concentrations for 50% mortality (LC50) and 90% mortality (LC90) of temephos against Cx. quinquefasciatus larvae were 0.18mg/l and 0.78mg/l, respectively. This finding also confirms resistance to temephos based on the WHO recommended instructions for resistance evaluation. CONCLUSION: Resistance to all groups of the tested insecticides should be considered for future vector control investigations in the study area.

A comprehensive review of cutaneous leishmaniasis in kerman province, southeastern iran-narrative review article.

BACKGROUND: Cutaneous leishmaniasis (CL) remains a serious public health concern in Kerman Province, eastern Iran. This study was aimed to conduct a comprehensive review and highlights various aspects of CL in the province of Kerman. METHODS: This article mainly focuses on the studies published in the past 26 years on CL in the province. Current data for the present status were obtained through the provincial health system. RESULTS: Bam was the most infected district (63.6%), followed by Kerman (24.7%) and other districts to a less extent. Leishmania tropica is the major causative agent (95.5%) of CL in Kerman province, however, L. major accounts for 4.5% of the total cases. Bam, Kerman and southern districts of Kerman province were purely anthroponotic CL (ACL), while Rafsanjan, Baft, and Sirjan showed both ACL and zoonotic CL (ZCL). In contrast, Orzoieh district was merely endemic to ZCL type. Phlebotomus sergenti was the main vector in ACL foci while Ph. papatasi was the major vector in the ZCL district of Orzoieh. Localized CL was the most prevalent form (80%) of the disease, while leishmaniasis recidivans was the most uncommon clinical manifestation (18.7%). CONCLUSION: Due to recent rises in CL disease both in regard of increases in incidence rate and expansion of the disease to new foci, and presence of various risk factors in the province, control measures and health strategies should have high priorities to help treat the existing cases and prevent the expansion of the disease to new areas.

The present status of cutaneous leishmaniasis in a recently emerged focus in South-west of kerman province, iran.

BACKGROUND: The objective of this study was to assess the magnitude of the cutaneous leishmaniasis (CL) disease and identification of the causative agent by nested-PCR for current control strategy. METHODS: This study was carried out as descriptive house-to-house visits in Orzoieh district in Kerman Province, south-east Iran, during 2011-2012. A questionnaire was completed for each individual consisting of demographic and clinical data. Suspected individuals were examined by direct smear microscopy and subsequent identification by nested-PCR. X(2) -test was used for any significance (P<0.05). RESULTS: A total of 18308 inhabitants (mean age; 22.7 yr) consisting of 9011 males (49.2%) and 9297 females (50.8%) were examined for the presence of active or chronic lesions. The overall prevalence was 4.7%, including 30 cases of active and 839 cases of scar, distributed more significantly (P<0.01) in females (5.2%) than males (4.3%). Individuals <10 years of age showed the highest (6.3%) and >50 years the lowest rate of CL disease, respectively (P<0.001). The proportion of infection was the highest in Soltanabad (14.7%), followed by Vakilabad (6.8%), Dolatabad (3.2%) and Shahmaran (2.8%). The majority of cases had 2 lesions (mean; 2.1 lesions). Hand was the most common site of involvement (35%), and then face (26%), and multiple locations (39%). Nested-PCR displayed 29 isolates as Leishmania major and one isolate L. tropica. The CL disease first emerged in 1998 as epidemic in the area and appeared endemics, thereafter. CONCLUSION: L. major was the sole species caused ZCL. These findings are necessary for future control programs and strategic planning.