Cases Of Anthroponotic Cutaneous Leishmaniasis Research Articles

Involvement of tryparedoxin peroxidase (TryP) and trypanothione reductase (TryR) in antimony unresponsive of Leishmania tropica clinical isolates of Iran

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.

Understanding the factors that determine the emergence of anthroponotic cutaneous leishmaniasis due to Leishmania tropica in Morocco: Density and mitochondrial lineage of Phlebotomus sergenti in endemic and free areas of leishmaniasis.

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.

Differential inflammatory responses associated with Leishmania major and Ltropica in culture.

Anthroponotic cutaneous leishmaniasis (ACL) due to Leishmania tropica and zoonotic CL (ZCL) due to Lmajor have different clinical and epidemiological features. To determine whether pro-inflammatory cytokines are involved in diverse pathogenicity of Leishmania species causing CL. The capacity of Lmajor/Ltropica to modulate expression of IL-1β, IL-8 (CXCL8), IFN-γ, TNF-α and MCP-1 (CCL2) in peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) was evaluated by real-time RT-PCR technique. PBMCs from both ZCL and ACL cases expressed significantly higher IFN-γ (P<.001) and TNF-α (P<.05) compared with healthy controls (HC). PBMCs from ACL patients expressed significantly higher IL-1β and IL-8 compared with ZCL patients and HC when stimulated with live Lmajor or Ltropica promastigotes (P<.001). After 4 and 10hours, Lmajor-infected MDMs expressed significantly higher IFN-γ (P<.05), and after 10hours, Ltropica-infected MDMs expressed significantly higher IL-1β, IFN-γ and IL-8 compared with noninfected cells (P<.05). This study shows differential parasite-mediated stimulations of the inflammatory response with Lmajor vs Ltropica ex vivo. Pro-inflammatory cytokines particularly IL-8 (CXCL8) and IL-1β might contribute in diverse clinical features of CL such as longer duration of lesion persistence in ACL patients.

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

BackgroundEpidemics 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.MethodsThis 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.ResultsA 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.ConclusionsThe 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.Graphical

Epidemiological Features of Cutaneous Leishmaniasis in Zliten (North West of Libya)

Cutaneous Leishmaniasis is endemic in north-west of Libya for long time and it’s spread to other new foci continues to involve new areas like Taurgha, Sirt and recently, Zliten. Most of the patients in north-west of Libya were infected with zoonotic Cutaneous Leishmaniasis, which caused by leishmania major, although some cases of anthroponotic cutaneous leishmaniasis caused by leishmania tropica were also reported. Zliten is a coastal city in the north west of Libya; with more than 289000 people; and now is known to be a new focus since 2016 when the sudden increase of the number of patients with Cutaneous Leishmaniasis had occurred.&#x0D; Aims: This study was performed to observe epidemiological changes about incidence, age of patients, geographical distribution in Zliten city over a period of last 2 year (2017 and 2018(.&#x0D; Study Design: Cross-sectional study as retrospective study over time of two years, involving all patients, who were presented or referred, to get management of Cutaneous Leishmaniasis, in three accredited outpatient departments for cutaneous leishmania (in Zliten). The data were collected and analyzed in Zliten Teching Hospital.&#x0D; Place and Duration of Study: Outpatient Department of Dermatology and Venereology of Zliten Teaching Hospital between 1st January 2017 and 31st December 2018.&#x0D; Methodology: The study included all patients (different gender and from all age groups) with Cutaneous Leishmaniasis, who sought medical advice in dermatology reference clinics in Zliten, over the period of 2 years (2017 and 2018). The main collected data were age, sex, number of lesions, and affected sites in the body, residency of the patients, year and month of presentation. The analysis of data was made with the use of Statistical Package for the Social Sciences (SPSS 25).&#x0D; Results: Eight hundred thirty nine patients were included in this study. The majority of patients came from Zliten and these represented 95.6%, while the most of them came from Majer (south eastern part of Zliten City with more than 25000 people living in it) and represented 45.5% of total patients with CL included in this study, followed by Al-juma (south western part of Zliten with around 52000 people), represented (28%) of total patients with CL.&#x0D; Males were found to be more affected, with male to female ratio, 2.4:1. The most affected age group were these less than forty with peak incidence at age group (20 yrs to 30 yrs). The registered patients in 2017 were 397, this number had increased slightly to be 440 in the following year (2018).&#x0D; The distribution of patients had shown seasonal variations, with steep increase in the number of cases in December, November and January.&#x0D; Conclusion: Cutaneous Leishmaniasis is remained to be a major health problem in Zliten, affecting a large number of population every year and need further study to determine molecular identification of parasites, and more efforts are needed to control the vector and reservoir.

Laboratory transmission of an Asian strain of Leishmania tropica by the bite of the southern European sand fly Phlebotomus perniciosus

Imported cases of anthroponotic cutaneous leishmaniasis due to Leishmania tropica are increasingly documented in Europe. We investigated the ability of Phlebotomus perniciosus, a competent vector of Leishmania infantum widespread in southwestern Europe, to support the growth and transmissibility of an Asian strain of L. tropica recently isolated from a refugee. Parasite growth behavior was investigated in laboratory-reared sand flies fed artificially with promastigotes as well as in sand flies infected after biting on footpad lesions induced in hamsters by promastigote inoculation. The evolution of infection was checked by gut microscopy and quantitative real-time PCR, and it was found to be similar between promastigote- and amastigote-initiated infections. In 80% of infected sand flies, despite survival and flourishing growth of promastigotes after blood digestion and defecation, either the parasites died, or failed to migrate to the foregut and/or to mature into infective forms. However, in the remaining 20% L. tropica developed into abundant metacyclic promastigotes. The quantitative real-time PCR assay detected variable loads of gut promastigotes irrespective of morphological evidence of viability or progressive/final death. Parasite transmissibility was investigated by exposing naive hamsters to P. perniciosus previously infected on chronic lesions induced in hamsters which survived to take a second blood meal. Two months post exposure, lesions developed in skin sites bitten by sand flies confirmed to harbor metacyclic promastigotes; in the following months, the presence of viable and transmissible L. tropica parasites in lesions was demonstrated by xenodiagnosis assays. Our findings support the hypothesis that, in particular epidemiological situations, P. perniciosus may play the role of an occasional L. tropica vector.

Distribution pattern of anthroponotic cutaneous leishmaniasis caused by Leishmania tropica in Western Afghanistan during 2013-2014

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.

Differential ecological traits of two Phlebotomus sergenti mitochondrial lineages in southwestern Europe and their epidemiological implications.

The introduction of leishmaniasis in a new area requires a well-established population of the sandfly vector species of the parasite. No autochthonous cases of anthroponotic cutaneous leishmaniasis have been detected in southwestern Europe, and Leishmania infantum is the only causative agent of leishmaniasis in this area. Phlebotomus sergenti, the main vector of Leishmania tropica, is commonly found in the Iberian Peninsula at sufficient densities to be able to act as a vector. It is characterised by high genetic diversity and classified in four mitochondrial lineages. Our aim was to analyse the composition and distribution of P. sergenti mitochondrial lineages in southwestern Europe given the possibility of phenotypic differences of biomedical importance between them. Sandflies were captured in the Iberian Peninsula and on the Canary and Balearic Islands. Mitochondrial lineage identification of 137 P. sergenti was performed using a novel PCR-RFLP that avoids the necessity of gene sequencing. Two lineages were evidenced, the typical Iberian one (lineage I) and another, held in common with North Africa (lineage III), that show a distinctive distribution. P. sergenti lineage I shows a better correlation to the bioclimatic diversity in southwestern Europe. Conversely, P. sergenti lineage III prefers warmer temperatures and less precipitation, which are typical of the Mediterranean. Lineage I seems to have adaptive advantages given its wider tolerance to temperature and altitude than lineage III, and it would seem more suitable to lead a potential geographical expansion towards the rest of Europe.

Epidemiological study on acute cutaneous leishmaniasis in Morocco

ObjectiveTo describe and compare the epidemiological features of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica, and zoonotic cutaneous leishmaniasis (ZCL) due to Leishmania major in Morocco. MethodsWe performed a retrospective study of ZCL and ACL cases reported during the last ten years in Morocco (2004–2013). Epidemiological data were analyzed by using Pearson's correlation method as well as Tukey test and digital maps were produced for incidence repartition calculated by using ArcMap GIS version 10. ResultsA total of 41656 cases of cutaneous leishmaniasis were notified between 2004 and 2013 in Morocco. The mean incidence was 139 cases/100000 population/10 years and it was significantly higher in 2010. In the spatial context, ACL form was the most common in Morocco, while ZCL was the most important in terms of the number of reported cases. For both forms, the highest incidence occurred in females and children (0–14 years). When analyzed according to the number of cases in each province, Errachidia (8728 cases) and Azilal (3523 cases) were the most affected by ZCL and ACL, respectively, while the highest incidence was noted in Zagora (231 cases/100000 population/10 years) and in Chichaoua (97 cases/100000 population/10 years), for ZCL and ACL, respectively. Maps of incidence repartition were performed to identify the risk area of ZCL and ACL. ConclusionsZCL and ACL are still major health problems in Morocco. We highlight the spatiotemporal change of cutaneous leishmaniasis incidence through the country during the last ten years and we underline the correlation between ZCL incidence and the percentage of rural population in Morocco.

An Exploratory Comparative Study of Recent Spatial and Temporal Characteristics of Cutaneous Leishmaniasis in the Hashemite Kingdom of Jordan and Syrian Arab Republic pre-Arab Spring and Their Health Policy Implications

Despite the worldwide spread of cutaneous leishmaniasis (CL) and its well-known impacts, it is still a highly neglected disease. The emergence and spread of CL could be affected by a multitude of social, economic, and environmental factors, which could be exacerbated by political instability as the case in the most recent Arab Spring. The present study aimed at studying in a retrospective manner the spatial and temporal characteristics of CL in the years from 1999 to 2010 pre-Arab Spring in two neighboring Middle East countries, namely the Hashemite Kingdom of Jordan (Jordan) and Syrian Arab Republic (Syria), in which Arab Spring has emerged with different responses from pro- and anti-governments groups and displacements of refugees occurred. Furthermore, discussion of health policy implications was incorporated in a concluding section. Descriptive non-spatial and spatial statistics analysis, trend surface analysis, clusters mapping analysis, and time-series analysis showed that the risk of CL varied remarkably spatially and temporally in both countries. Overall, the patterns of the disease in Jordan could be described as relatively low and heterogeneous while those in Syria were relatively much higher and less heterogeneous. Moreover, the northwestern parts of Syria formed a relatively hotspot while the southern parts of Syria and northern parts of Jordan formed a relatively cold spot. Also, in both countries the risk of acquiring CL showed general temporal trends of increase although in Syria the trend was much faster than that in Jordan. In addition, it was found that the number of CL cases reported in winter was much higher than those reported in summer in both countries. However, the onset of the Arab Spring might lead to modifications of these patterns through increasing the risk of the disease spatially and temporally and modifying the major forms of the disease as more anthroponotic CL cases might be reported in Jordan and more zoonotic CL cases might be reported in Syria. Therefore, there is an urgent need for developing scientifically-based, standardized, and informed national health policies and action plans for combating CL in both countries. As the Syrian crisis is not only affecting Jordan but also other neighboring countries in the Middle East, it is important to study the situation with respect to CL in the whole Middle East pre- and post-Arab Spring and also develop integrated national health policies and action plans for combating the disease in the region.

Spatial distribution of phlebotomine sand flies in the Aydin Mountains and surroundings: the main focus of cutaneous leishmaniasis in western Turkey

An entomological survey was conducted to determine the spatial distribution of phlebotomine fauna and understand the effect of environmental factors. The entomological survey was carried out during 2006-2007 in a study area in the rural area of Aydin province, near the Kusadasi town where VL, CL, and canine leishmaniasis (CanL) are endemic. In 2006 and 2007, 132 locations were sampled using sticky traps mainly on embankments. Detailed environmental and meteorological information was also collected for each location. The results of entomological studies indicated that the probable vectors are Phlebotomus tobbi and P. neglectus for VL and CanL, and P. similis for CL in this western leishmaniasis focus. The data revealed a correlation between their presence and spatial variables such as altitude, sampling site location, and humidity. The distribution areas of probable vector species in this study area allowed the identification of risk levels, which may provide useful information to guide the leishmaniasis research in endemic regions.

Zoonotic cutaneous leishmaniasis outbreak in Mazar-e Sharif, northern Afghanistan: An epidemiological evaluation

In 2005, 200 cases of zoonotic cutaneous leishmaniasis (ZCL) were recorded among International Security Assistance Force (ISAF) troops stationed in the Mazar-e Sharif airport area. Within the local population, investigations revealed 3782 cases of ZCL, 174 cases of anthroponotic cutaneous leishmaniasis (ACL), and 2 cases of visceral leishmaniasis (VL) in the period from March 21, 2004 to March 20, 2005, and 4045 cases of ZCL, 198 cases of ACL, and no cases of VL from March 21, 2005 to March 20, 2006. The previously unknown transmission dynamics of ZCL, and differing seasonal distribution of ZCL and ACL, are here defined, thus permitting quantification and prediction of infection rates in deployed troops for the first time. At Mazar-e Sharif, Phlebotomus papatasi and Rhombomys opimus occurred in the highest densities yet observed, together with record-high Leishmania major infection rates. Data indicate the existence of high-density, anthropogenically induced ZCL in Afghanistan.

Zoonotic Cutaneous Leishmaniasis, Afghanistan

Zoonotic Cutaneous Leishmaniasis, Afghanistan

Anthroponotic cutaneous leishmaniasis in Tunisia: Presence of Leishmania killicki outside its original focus of Tataouine

The first three documented cases of anthroponotic cutaneous leishmaniasis due to Leishmania killicki are reported from locations outside the original focus of Tataouine in southeast Tunisia. Three strains were isolated from three patients from Gafsa, Sidi Bouzid and Seliana indicating an extension of this parasite's range towards the centre and the north of Tunisia.

Epidemiology of anthroponotic cutaneous leishmaniasis in Afghan refugee camps in northwest Pakistan

During November and December 1998, 16 Afghan refugee camps were surveyed for anthroponotic cutaneous leishmaniasis (ACL). Prevalence of active lesions and scars amongst the population was 2.7% and 2.4%, respectively. Between camps the prevalence of active lesions varied from 0.3 to 8.8% and that of scars from 0.3 to 5.8%. Random-effects logistic regression indicated that risk of active ACL was associated with age but not gender. This model also indicated a significant clustering at the household level. The average annual force of ACL infection was estimated to be 0.046 per year (4.6 cases/1000 persons/year) over the past 10 years. Based on the evidence from this study an intervention strategy was formulated for all camps with reported ACL cases. This includes targeting of active cases with insecticide-treated nets, sold at a highly subsidised price.

A randomized controlled trial of insecticide-treated bednets and chaddars or top sheets, and residual spraying of interior rooms for the prevention of cutaneous leishmaniasis in Kabul, Afghanistan

Anthroponotic cutaneous leishmaniasis (ACL) is a significant public health problem in many towns and cities of south central Asia and the Middle East, resulting in disfigurement and disability which warrants preventive action. A randomized controlled trial was conducted in 1997/98 amongst a non-immune study population of 3666 people in Kabul, Afghanistan, to compare the efficacy of insecticide-treated nets (ITNs), insecticide-treated Islamic cloth wraps ( chaddars) used to sleep in, and residual pyrethroid spraying of individual houses for the prevention of ACL. Dosages of insecticide were: ITNs with permethrin, 0·5 g/m 2; chaddars with permethrin, 1 g/m 2; rooms with lambdacyhalothrin, 30 mg/m 2. Cases of ACL were diagnosed on clinical criteria. At the end of the trial period (15 months) the incidence of ACL amongst controls was 7·2%, amongst ITN users 2·4% (OR 0·31, 95% CI 0·2–0·5), amongst impregnated chaddar users 2·5% (OR 0·33, 95% CI 0·2–0·6) and amongst residents of sprayed houses 4·4% (OR 0·60, 95% CI 0·3–0·95). ITNs and impregnated chaddars were equally effective, providing about 65% protective efficacy, with approximately 40% protective efficacy attributable to individual house spraying. No significant differences for age or sex were found between new cases in the intervention and control groups. No serious side-effects were reported and interventions were generally popular; ITNs were the most popular, followed by residual spraying and then impregnated chaddars.

Serodiagnosis and epidemiology of visceral leishmaniasis in Turkey.

Infantile Mediterranean visceral leishmaniasis (IVL) and anthroponotic cutaneous leishmaniasis (ACL) have long been known to exist in the western and southeastern Turkey, respectively. To further study these and other related diseases, a recombinant antigen (rK39) specific to VL was used in an ELISA for serodiagnosis of selected patients and for screening dog reservoir populations in several endemic sites. Among 24 confirmed VL cases from western Turkey, the rK39 ELISA proved to be more sensitive than a combination of cultivation and microscopy of bone marrow aspirates. The specificity of rK39 for leishmaniasis was demonstrated by its lack of cross-reactivity with sera from other human diseases in the same sites. Interestingly, six of the 83 parasitologically proven ACL cases from southeast Turkey were also rK39 positive. The end point titers of the positive VL and CL cases vary from 10(-2) to 10(-5) and from 10(-2) to 10(-3), respectively. The rK39 ELISA was also used to screen 494 apparently healthy dogs from Urfa in southeast Turkey, Manisa/Alasehir near the Aegean Sea, and Karabuk near the Black Sea. Eighteen rK39-positive cases (3.6%), all from the latter two areas, were found to have varying endpoint titers (10(-2)-10(-4)). The high titers predicted increased severity and frequency of the clinical symptoms (i.e., lymphadenopathy, depilation, skin lesion, weight loss and/or death), which were manifested subsequently in 16 of these 18 cases. In addition, more positive canine cases were diagnosed by the rK39 ELISA preclinically than the procedures to detect parasites postsymptomatically in the lymph node aspirates. The use of the rK39 ELISA as a sensitive tool makes it possible to demonstrate coendemicity of canine and human VL, as expected in the case of IVL. The results also point to the possible presence of additional VL types in western Turkey and cutanovisceral type in the southeast part of this country.