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Anthroponotic cutaneous leishmaniais (ACL) and zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania tropica and Leishmania major, respectively, are endemic vector-borne diseases in southern Saudi Arabia. In 2021, an outbreak of cutaneous leishmaniasis occurred in the province of Asir. The main objective of our investigation was to analyze the epidemiological features of CL in southern Saudi Arabia. The ministry of health recorded 194 CL patients between January and December 2021 from the Asir province. Our findings showed that the majority of CL patients (87.1%) originated from the governorates of Khamis-Mushait and Abha. Most of the patients were males (62.3%). While CL affected all age groups, those under 13 years old were the most affected (38.1%). For both genders, CL patients were mostly Saudi citizens (90.7%) compared to non-Saudi expatriates. The majority of CL patients (75.2%) suffered from a single lesion, and the majority of lesions (61.3%) were located on the face. The seasonal prevalence of CL showed two peaks, a small one in July-August and a larger one in March. Of a total of 194 Giemsa slides samples, 188 showed positive amplification of Leishmania ITS1 gene. Based on PCR-RFLP and PCR-HMR, 183 patients showed positive amplification of L. tropica and five patients showed positive amplification of L. major. Phylogenetic analysis revealed a clear distinct separation between L. major and L. tropica sequences. Our results provided strong evidence of the pre-domination of L. tropica, the main etiological agent of ACL in Asir province. We reported for the first time the presence of L. major, an etiological agent of ZCL in the study areas. The co-circulation of ACL and ZCL highlighted the complexity of the epidemiology of CL in southern Saudi Arabia, and subsequently, further studies to identify competent vectors and reservoir hosts for the establishment of control strategies are needed.
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The appearance of resistance to pentavalent antimony, as the mainline of treatment for Cutaneous Leishmaniasis (CL) has been reported from Iran. According to the patients' laboratory and clinical history, 96 archived slides of patients infected with Leishmania tropica (L. tropica) treated with Meglumine Antimoniate (Glucantime®) were selected. After microscopic examination, Nested Polymerase Chain Reaction (Nested-PCR) and Restriction Fragment Length Polymorphism (RFLP) assays were done for each sample. In Nested-PCR, all positive samples were characterized as L. tropica. Additionally, some positive products of sensitive, resistant, and recidivans cases were selected to check their differentiations by sequencing software. In RFLP, various patterns of schizodemes were detected according to the reference patterns. Most sensitive cases of L. tropica (treated with Glucantime®) were categorized as schizodeme B, and most resistant cases were identified as schizodeme B and D. In recidivans cases, 91% of specimens categorized as schizodeme A and B. However, study on the type of L. tropica isolates that are resistant or sensitive to Glucantime® could be helpful before drug therapy.
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BACKGROUND: Leishmaniases are a vector-borne disease, re-emerging in several regions of the world posing a burden on public health. As other vector-borne diseases, climate change is a crucial factor affecting the evolution of leishmaniasis. In Morocco, anthroponotic cutaneous leishmaniasis (ACL) is widespread geographically as many foci across the country, mainly in central Morocco. The objective of this study is to evaluate the potential impacts of climate change on the distribution of ACL due to Leishmania tropica, and its corresponding vector Phlebotomus sergenti in Morocco. METHODS: Using Ecological Niche Modeling (ENM) tool, the estimated geographical range shift of L. tropica and P. sergenti by 2050 was projected under two Representative's Concentration's Pathways (RCPs) to be 2.6 and RCP 8.5 respectively. P. sergenti records were obtained from field collections of the laboratory team and previously published entomological observations, while, epidemiological data for L. tropica were obtained from Moroccan Ministry of Health reports. RESULTS: Our models under present-day conditions indicated a probable expansion for L. tropica as well as for its vector in Morocco, P. sergenti. It showed a concentrated distribution in the west-central and northern area of Morocco. Future predictions anticipate expansion into areas not identified as suitable for P. sergenti under present conditions, particularly in northern and southeastern areas of Morocco. L. tropica is also expected to have high expansion in southern areas for the next 30 years in Morocco. CONCLUSION: This indicates that L. tropica and P. sergenti will continue to find suitable climate conditions in the future. A higher abundance of P. sergenti may indeed result in a higher transmission risk of ACL. This information is essential in developing a control plan for ACL in Morocco. However, future investigations on L. tropica reservoirs are needed to confirm our predictions.
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Leishmania tropica , Leishmaniasis Cutánea , Phlebotomus , Psychodidae , Animales , Cambio Climático , Insectos Vectores , Leishmaniasis Cutánea/epidemiología , Marruecos/epidemiologíaRESUMEN
Clinical resistance to pentavalent antimonial compounds has long been recognized as a major problem in the treatment of human leishmaniasis. Trypanothione metabolism, the main form of thiol, has shown to play a central role in antimony resistance of laboratory-generated resistant Leishmania spp. and field-isolated resistant L. donovani; but the mechanism of antimony resistance in the clinical isolates of L. tropica causing anthroponotic cutaneous leishmaniasis (ACL) is less studied. Patients were selected among confirmed positive ACL cases who referred to Pasteur Institute of Iran, Tehran, from endemic regions of north-east and south of Iran. L. tropica clinical isolates were collected from patients who were either treatment-responsive (MAS=S1 to S5) or unresponsive (MAR=R1 to R4) to Glucantime® (meglumine antimoniate=MA). Isolates were tested for sensitivity to trivalent antimony (SbIII) in promastigotes and to pentavalent antimony (SbV) in intracellular amastigotes stages. Intracellular thiol levels were assayed and trypanothione-dependent components, including trypanothione reductase (TR) and tryparedoxin peroxidase I (TryP) were analysed at protein level and enzymatic activity in isolates. The MAR isolates had an approximate two fold increase in the levels of intracellular thiols (P< 0.05) accompanied by an average 5-10 fold increase in in vitro resistance to antimony. TryP was amplified at the protein level in all MAR strains as compared to the MAS strains (range: 2.8-5.6 fold). All MAR isolates metabolized H2O2 at higher rates than MAS isolates (8.55±0.75 nmol/min/mg vs. 3.14±0.36 nmol/min/mg) (P< 0.05). In addition, levels of TryR protein were also markedly elevated in 3 out of 4 MAR isolates (range: 2.2-4.1 fold). This was accompanied by overexpressed TryR activity (mean level of 46.83±2.43 for extracts of MAR vs. 20.98±3.02 for MAS strains) (P< 0.05). Elevated levels of TryP, active enzyme in peroxide detoxification, were observed in MAR parasites resulting in an increased metabolism of H2O2. TryR activity was overexpressed on average in extracts of MAR strains, but not in all isolates. Enhanced anti-oxidant defenses through thiol metabolism may play a significant role in clinical resistance of ACL patients to Glucantime.
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Antiprotozoarios , Leishmania tropica , Leishmaniasis Cutánea , Antimonio/farmacología , Antimonio/uso terapéutico , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Resistencia a Medicamentos , Humanos , Peróxido de Hidrógeno/uso terapéutico , Irán , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Antimoniato de Meglumina/uso terapéutico , NADH NADPH Oxidorreductasas , Peroxidasas , Extractos Vegetales/uso terapéutico , Proteínas Protozoarias , Compuestos de SulfhidriloRESUMEN
Anthroponotic cutaneous leishmaniasis (ACL) due to Leishmania tropica is spreading to new areas in Morocco. Exposure to the vector, Phlebotomus sergenti, is the only proven risk factor. Our objective was to compare the densities and genetic characteristics of P. sergenti populations in two nearby localities in Morocco, one in an ACL endemic area (El Borouj) and another in a nonendemic area (Sidi Hajjaj). P. sergenti density was significantly higher in the endemic area than in the nonendemic town (p = 0.032). A different predominant P. sergenti mitochondrial lineage was evidenced in each one of the two localities, and for the first time, the P. sergenti lineage acting as a vector of L. tropica has been identified. Bioclimatic differences were detected between both localities. In conclusion we found differences in both the density and the mitochondrial lineage of P. sergenti populations that may explain the different epidemiological situation. Given that the density of P. sergenti in the locality without ACL cases seems sufficient to allow transmission, the main factor that would justify its nonendemic character could be the absence of P. sergenti Lineage IV, which seems to prefer warmer and drier climates.
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Leishmania tropica , Leishmaniasis Cutánea , Phlebotomus , Animales , Leishmania tropica/genética , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/veterinaria , Marruecos/epidemiologíaRESUMEN
Cutaneous leishmaniasis (CL), caused by Leishmania tropica, is the main causative agent of CL in the Herat province, western Afghanistan. In CL patients, one of the most important indicators for reducing the amount of body damage and the choice of treatment is the number of dermal lesions, but there is no strong evidence in this regard. Therefore, using count regression models, the main objective of this historical cohort study was to identify the distribution of the number of dermal lesions and determine the associated factors among CL patients referring to leishmaniasis reference laboratory in Herat province, from January 2012 to December 2013. In a total of 4,127 clinically suspected CL cases, 50.20% were female and 49.80% male. Based on the results of ZINB model, which is the best model suggested by goodness-of-fit criteria, age variables (IRR = 1.007), duration of lesion (6-12 weeks compared to < 6 weeks with IRR = 1.36 and >12 weeks with IRR = 1.39 compared to <6 weeks), type of lesion(both nodule and ulcer compared to papule with IRR = 2.03), location of lesion (trunk with IRR = 1.90, upper with IRR = 1.66, lower with IRR = 1.61 and mix with IRR = 10.35 compared to head/neck/ears) and type of lesion (ulcer compared to papule with IRR = 0.50, nodule and lupoid, respectively, as IRR = 0.72 and IRR = 0.51 compared to papule) had a significant effect on the mean number of dermal lesions (p < .05). Also, our results showed that among four models used, the ZINB model represented a better performance to determine the associated probable factors about the number of dermal lesions in ACL patients. Moreover, there was a direct association between age and number of dermal lesions; in addition, duration of lesion, type of lesion and location of lesion had a significant effect on the number of dermal lesions. Therefore, a comprehensive planning is necessary for controlling and reducing the number of dermal lesions.
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Leishmaniasis Cutánea/patología , Piel/patología , Adolescente , Adulto , Afganistán , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Leishmania tropica/fisiología , Masculino , Persona de Mediana Edad , Modelos Teóricos , Estudios Retrospectivos , Adulto JovenRESUMEN
The objective of the present study was to compare the host's immune responses between unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis (ACL) treated by meglumine antimoniate. A case-control study was carried out in an endemic focus in Iran. Blood samples were taken from patients and peripheral blood mononuclear cells (PBMCs) were isolated. Two wells were considered for each isolate of unresponsive and responsive patients; one was exposed to L. tropica (Lt-stimulated cells) and the other remained non-exposed (non-stimulated cells). After 24â¯h of incubation, whole RNA was extracted from each sample. Real-time quantitative PCR was carried out to confirm the differences in expression levels of IL-12 P40, IFN-γ, IL-1ß, IL-4 and IL-10 among isolates. Data were analyzed and Pâ¯<â¯0.05 was considered to be statistically significant. In our study, Lt-stimulated cells and non-stimulated cells in unresponsive groups demonstrated significantly lower expression levels of IL-1ß, IL-12 P40 and IFN-γ genes and higher expression levels of IL-4 and IL-10 genes, compared to Lt-stimulated cells and non-stimulated cells in responsive groups. There was a negative correlation between IL-12 P40 with IL-10 and IL-1ß with IL-10 in ACL Lt-stimulated cells in unresponsive group, while a positive correlation between IL-12 P40 with IL-1ß and IL-12 P40 with IFN-γ in ACL Lt-stimulated cells in responsive group. Probably, different immune responses caused by various factors play a major role in the pathogenesis and development of unresponsiveness in ACL patients. The profile and timing of cytokine production correlated well with the treatment outcome of Leishmania infection.
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Antiprotozoarios/uso terapéutico , Leishmania tropica/fisiología , Leishmaniasis Cutánea/tratamiento farmacológico , Leucocitos Mononucleares/efectos de los fármacos , Antimoniato de Meglumina/uso terapéutico , Estudios de Casos y Controles , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Enfermedades Endémicas , Femenino , Regulación de la Expresión Génica , Humanos , Mediadores de Inflamación/metabolismo , Irán , Leucocitos Mononucleares/fisiología , Masculino , Células TH1/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: All types of the Old World's leishmaniasis were endemic on the territory of the South regions of ex-USSR. Epidemiological situation was well under control during the USSR era, due to implementation of complex anti-leismaniasis measures. These interventions were dramatically stopped as a result of the collapse of the USSR. METHODS: Most relevant publications on epidemiology and control of leishmaniases in the Republics of Central Asia and Transcaucasia of the ex-USSR were screened. RESULTS: Within the endemic area, the foci of different kinds of leishmaniasis are often overlapped thus calling for deployment of integrated measures. The anthroponotic cutaneous leishmaniasis (ACL) was reported in settlements and towns of Central Asia and Transcaucasia of the ex-USSR. The natural foci of cutaneous leishmaniasis were widespread in the desert of Turkmenistan, Uzbekistan, Kazakhstan and Tajikistan. The northern boundary of the zoonotic cutaneous leishmaniasis (ZCL) area coincided with the northern boundary of the distribution of great gerbils - the main reservoir of this infection in the ex-USSR. Visceral leishmaniasis (VL) occurred in the Central Asian Republics and in the republics of the Transcaucasia. Holistic approach was adopted by the programs targeting the source of infection, vector(s) and man. CONCLUSION: The presence rise in the number of cases of different types of leishmaniasis in the ex-USSR strongly necessitates that health authorities should consider these diseases as an important public health problem. The immediate task would be rebuilding a comprehensive surveillance system consisting of active and passive case detection mechanism along with immediate treatment of the patients.
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Anthroponotic cutaneous leishmaniasis (ACL), caused by Leishmania tropica, is the main cause of cutaneous leishmaniasis (CL) in the Herat province, Western Afghanistan. We investigated the role of environmental factors on ACL distribution in Herat. Epidemiological data from 2457 patients were retrieved from the local WHO sub-office. Shapefile layers of districts, cities, villages, land cover, soil type and digital elevation model (DEM) of the Herat province were used to assess, by logistic regression modelling, the effects of land cover, soil types, elevation, and proximity to the Harirud river on the distribution of ACL. The key determinants of distribution were: (i) close proximity to the Harirud river, (ii) elevation between 700 and 1200m, (iii) intensive and intermittent irrigated cultivated land, and (iv) Haplocalcids with Torriorthents and Torrifluvents soil types. No ACL cases were found below 700m, and a few cases were present at >1200m in irrigated areas around the Harirud river. These findings suggest that moist soil and the humidity from irrigated areas found between 700 and 1200m provide suitable breeding sites of Phlebotomus sergenti, the main sandfly vector of L. tropica in Afghanistan. The effect of elevation also explains the predominance of ACL over ZCL in this region. The present study showed that distribution of ACL is strongly associated with environmental factors in West Afghanistan where the political and socio-economic conditions may also affect the epidemiology of CL.
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Leishmania tropica , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/parasitología , Adolescente , Adulto , Afganistán/epidemiología , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Reservorios de Enfermedades , Femenino , Humanos , Humedad , Lactante , Insectos Vectores , Leishmaniasis Cutánea/transmisión , Masculino , Persona de Mediana Edad , Phlebotomus , Suelo , Adulto JovenRESUMEN
BACKGROUND: Establishment of sand flies laboratory colonies is essential to understand various biological aspects of Phlebotominae sand flies. The aims of the current study were to establish the colony of Phlebotomus sergenti Parrot (1917), the main vector of anthroponotic cutaneous leishmaniasis in old world, and to study biological parameters of this species. METHODS: The sand flies were reared at 26-28 °C temperature, 14:10 (light: dark) photoperiod and 70-80% relative humidity. Larval diet was a composted mixture of rabbit faces and rabbit pellets which is prepared through a special process. First to fifth generations of P. sergenti were used to define biological parameters. RESULTS: Results showed that, P. sergenti blood feeding percentage were 42% on chicken, 21% on BALB/c and 37% on golden hamster. Average time of blood digestion, egg incubation, 1st instar larva, pupa and adult emerging was recorded at 3.4, 8.7, 15, 33.3 and 41.2 days after blood feeding, respectively. Mean number of laid eggs was 55.1 and retained eggs were 35 per a female. Fecundity and production rate were 61.6%, and 42.2% respectively. Average longevity recorded at 15.2 days for females and 14.8 days for males. CONCLUSION: Colony of P. sergenti has been established for the first time in Iran. Average interval time from egg to adult of this species was 32.5 days. Chicken and golden hamster were recommended as a blood source for colony initiation and routine blood feeding, respectively.
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A simple efficacious topical treatment for cutaneous leishmaniasis (CL) is still an unresolved challenge. This study aimed to evaluate the efficacy of the topical use of thioxolone plus benzoxonium chloride (Thio-Ben) tincture in combination with cryotherapy in comparison with intralesional meglumine antimoniate (Glucantime) along with cryotherapy in treating anthroponotic CL (ACL). The study was conducted in Leishmaniasis Center in Dadbin Health Care Clinic, Kerman, Iran. Sixty-four CL lesions were randomly assigned to receive Thio-Ben plus cryotherapy (TC) (n = 32) or Glucantime plus cryotherapy (GC) (n = 32). Thio-Ben was used topically every other day and Glucantime was used intralesionally once a week for a maximum of 3 months. In both study groups, cryotherapy was administered using liquid nitrogen once every 2 weeks. Of 64 recruited lesions, 47 lesions completed the study protocol. Twenty lesions (91%) in TC group and 23 lesions (92%) in GC group showed complete cure. TC group showed faster clinical response. Pain, hypersensitivity reaction, dizziness, and nausea were only seen in GC group. This study showed that the topical use of Thio-Ben combined with cryotherapy has a good efficacy in treating ACL with the benefit that Thio-Ben has more patient compliance and less side effects than intralesional Glucantime.
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Antiinfecciosos Locales/administración & dosificación , Compuestos de Benzalconio/administración & dosificación , Crioterapia , Lactonas/administración & dosificación , Leishmaniasis Cutánea/terapia , Adolescente , Adulto , Antiprotozoarios/administración & dosificación , Niño , Preescolar , Terapia Combinada , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Irán , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/parasitología , Masculino , Meglumina/administración & dosificación , Antimoniato de Meglumina , Datos de Secuencia Molecular , Compuestos Organometálicos/administración & dosificación , Cooperación del Paciente , Recurrencia , Inducción de Remisión , Método Simple Ciego , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The objective of this study was to assess the epidemiological characteristics of a new emerging focus of cutaneous leishmaniasis (CL) in southern villages of Bam District, southeastern Iran, 2010. METHODS: A house-to- house census survey of 5544 individuals were interviewed and physically examined for the presence of active lesions or scars. Diagnosis was confirmed by direct smears, cultures and identification by PCR. The data were entered into a computer and SPSS ver. 15. RESULTS: Overall, 1.2% of the inhabitants were infected, 0.5% active and 0.7% scars and females were more significantly infected (1.7%) than males (0.8%), (P= 0.003). All age groups were equally affected. Most of the lesions were on the face and majority had single lesion. Most of the cases appeared from 2006 to 2008 during the CL epidemic in the city of Bam. PCR indicated L. tropica as the causative agent. CONCLUSION: The presence of non-immune individuals along with suitable ecological conditions could induce a new emerging focus of ACL in villages.