Zoonotic Cutaneous Leishmaniasis Cases Research Articles

Seasonal Patterns of Zoonotic Cutaneous Leishmaniasis Caused by L. major and Transmitted by Phlebotomus papatasi in the North Africa Region, a Systematic Review and a Meta-Analysis

In North African countries, zoonotic cutaneous leishmaniasis (ZCL) is a seasonal disease linked to Phlebotomus papatasi, Scopoli, 1786, the primary proven vector of L. major dynamics. Even if the disease is of public health importance, studies of P. papatasi seasonal dynamics are often local and dispersed in space and time. Therefore, a detailed picture of the biology and behavior of the vector linked with climatic factors and the framework of ZCL outbreaks is still lacking at the North African countries' level. Our study aims to fill this gap via a systematic review and meta-analysis of the seasonal incidence of ZCL and the activity of P. papatasi in North African countries. We address the relationship between the seasonal number of declared ZCL cases, the seasonal dynamic of P. papatasi, and climatic variables at the North African region scale. We selected 585 publications, dissertations, and archives data published from 1990 to July 2022. The monthly incidence data of ZCL were extracted from 15 documents and those on the seasonal dynamic of P. papatasi from 11 publications from four North African countries. Our analysis disclosed that for most studied sites, the highest ZCL incidence is recorded from October to February (the hibernal season of the vector), while the P. papatasi density peaks primarily during the hot season of June to September. Overall, at the North African region scale, two to four months laps are present before the apparition of the scars reminiscent of infection by L. major. Such analysis is of interest to regional decision-makers for planning control of ZCL in North African countries. They can also be a rationale on which future field studies combining ZCL disease incidence, vector activity, and climatic data can be built.

An outbreak of cutaneous leishmaniasis due to Leishmania major in an endemic focus in central Iran.

Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania major is an important endemic disease and a major public health concern in Iran. Following an outbreak of leishmaniasis in 2013 in one of the important foci in Iran, the researchers were prompted to determine the underlying causes of the epidemic. Adult sand flies were collected using sticky traps and aspirating tubes and infection with Leishmania parasites was evaluated. Also, rodents were captured using Sherman live traps and stray dogs were hunted and were tested for the presence of leishmanial infection. Active case detection was also conducted and data related to each household were recorded using a researcher-designed form. Nested PCR and PCR-RLFP techniques were employed to determine Leishmania infection in the samples. Phlebotomus papatasi was the most dominant species among the 7 different species of sand flies collected in this study. Sergentomyia clydei, Sergentomyia theodori, and Sergentomyia grekovi were identified for the first time in the study area. 20% of collected Ph. papatasi species and one Meriones libycus were infected with Leishmania major. Stray dogs demonstrated no lesions on different parts of their body. The relative frequency of active lesions and scars on the dogs were respectively 5.49% and 1.23% in 2013 and 5.82% and 0.56% in 2014. The highest number of ZCL cases due to L. major was recorded in Ardestan city. Phlebotomus papatasi is the main vector and M. libycus seems to be the primary reservoir host of ZCL in the suburbs of this city. Furthermore, due to the low density of rodent reservoir hosts in the study area, we support the hypothesis that humans may have had a role in maintaining the parasite cycle in the population.

Spatial modeling of zoonotic cutaneous leishmaniasis with regard to potential environmental factors using ANFIS and PCA-ANFIS methods

This study compares two adaptive neuro-fuzzy inference system (ANFIS) and principal component analysis (PCA)-ANFIS techniques for spatial modeling and forecasting of zoonotic cutaneous leishmaniasis (ZCL) cases in rural districts of Golestan province, Iran. We collected and prepared data on ZCL cases and climatic, topographic, vegetation, and human population factors. By applying the PCA algorithm, the parameters affecting the ZCL incidence were decomposed into principal components (PCs), and their dimensions were reduced. Then, PCs were used to train the ANFIS model. To evaluate the proposed approaches in model assessment phase, we used test data in 2016. In this phase, we showed that PCA-ANFIS model with values ​​of R2 = 0.791, MAE = 0.681, RMSE = 0.904 compared to ANFIS model with values ​​of R2 = 0.705, MAE = 0.827, RMSE = 1.073 has better performance in prediction of the ZCL cases. Actual and predicted maps of ZCL cases in 2016 by both models demonstrated that the high-risk regions of the disease are located in the northeastern, northern parts, and some central rural districts of Golestan province. Sensitivity analysis of the ANFIS model showed that population, vegetation, average wind speed, elevation, and average soil temperature, respectively, are the most significant factors in predicting the ZCL cases. The findings indicated the importance of machine learning (ML) techniques (ANFIS and PCA-ANFIS) in medical geography studies. By using these approaches, with less cost and shorter time, high-risk areas of diseases can be predicted, and the most effective factors on the spatial prediction of diseases can be identified. Public health policymakers can use these useful tools to control and prevent the disease and to allocate resources to disease-prone areas.

The study of P-glycoprotein A, G-glutamylcysteine synthetase 1, and aquaglyceroporin 1 genes expression in non-healing zoonotic cutaneous leishmaniasis cases

Background and aims: Regarding the increasing numbers of clinical antimonial-resistant Leishmaniasis, understanding the reasons for drug resistance is helpful. This study aimed to find the expression level of the genes related to resistance, P-glycoprotein A (PgpA), G-glutamylcysteine synthetase 1 (Gsh1), and aquaglyceroporin 1 (Aqp1) in antimonial-resistant clinical isolates. Methods: Samples were isolated from leishmaniasis ulcers of 10 non-healing patients and the species were identified by the nested-polymerase chain reaction (PCR) method. In vitro experiments were performed using the amastigote-macrophage model by J774 cell line, and in vivo studies were conducted by animal model, the Balb/c mice. Finally, the values of genes expression were determined by quantitative-reverse transcription (q-RT) real-time PCR method and then compared with non-resistant Leishmania major (MRHO/IR/75/ER). Results: Molecular identification showed that all isolated protozoa were L. major. The isolated samples from clinical resistant patients represented no increase in expression in the tested resistance genes (P>0.05). Finally, it was found that the lack of improvements in patients was not associated with the increased expression of resistance genes. Conclusion: In general, no inherent resistance was observed in the tested samples neither a correlation between the healing of lesions and the level of genes expression.

Risk Assessment of the Role of the Ecotones in the Transmission of Zoonotic Cutaneous Leishmaniasis in Central Tunisia.

Zoonotic cutaneous leishmaniasis (ZCL), endemic in Central and Southern Tunisia, is caused by Leishmania major (Kinetoplastida: Trypanosomatidae), which is transmitted by the sand fly Phlebotomus papatasi. In Tunisia, the fat sand rat Psammomys obesus and the desert jird Meriones shawi are the principal reservoir hosts of L. major. The presence of the P. papatasi vector of the L. major etiologic agent of ZCL was assessed in the vicinity of villages in endemic areas of Central Tunisia. The study was performed from September through October 2019, a period corresponding to the main peak of activity of P. papatasi. Sand flies were collected from rodent burrows located at the ecotone level, which is the transition zone between the natural environment and human settlement. Sand flies were identified to species level and tested for the presence of L. major by PCR. Our entomological survey showed that P. papatasi is the most abundant sand fly species associated with rodent burrows, and this abundance is even higher in ecotones primarily occupied by P. obesus in comparison to ecotones occupied by M. shawi. Infections with Leishmania major were detected only in P. papatasi, with an overall minimum infection rate (MIR) of 2.64%. No significant difference was observed between the MIRs in ecotones of P. obesus and of M. shawi. Incidence of ZCL in the studied areas ranged from 200 to 700 cases per 100,000 inhabitants, with a mean incidence of 385.41 per 100,000. Higher ZCL incidence was identified in ecotones of M. shawi compared to ecotones of P. obesus. ZCL cases are positively correlated with the MIRs. Considering the short flight range of P. papatasi, increases in its densities associated with burrows of P. obesus or M. shawi at the ecotone level expand the overlap of infected vectors with communities and subsequently increase ZCL incidence. Therefore, control measures should target P. papatasi populations at the ecotones.

Zoonotic cutaneous leishmaniasis and Leishmania infection among Meriones shawi population in Setif Province, Algeria

Abstract. Fellahi A, Djirar N, Cherief A, Boudrissa A, Eddaikra N. 2021. Zoonotic cutaneous leishmaniasis and Leishmania infection among Meriones shawi population in Setif Province, Algeria. Biodiversitas 22: 2547-2554. Zoonotic cutaneous leishmaniasis (ZCL) is the most endemic disease in Algeria. Leishmania major is the causative agent, and Gerbils Meriones shawi and Psammomys obesus are the main reservoir hosts. The Province of Setif in Algeria has become a very active focus for this zoonosis. Our study was carried out from January 2017 until January 2019 in ten representative stations of the study area, with an aim to identify the association between zoonosis and reservoir host species. Eighty-six (86) specimens of M. shawi and three (3) specimens of P. obesus were captured and determined. Superficial lesions were subjected to Giemsa stained smears. In addition, Livers and spleens were tested for Leishmania DNA using ITS1 PCR. The results showed the presence of M. shawi in almost all communities of Setif Province and the highest population with 50 specimens (58.13%) was in the center and south. The microscopic and molecular detection of Leishmania showed high infestation in most specimens of Meriones (32/86) with a rate of 37.20 %, however, no infestation in Psammomys has been detected. The PCA results showed a negative association between rainfall and ZCL cases; however, positive association was found between temperature and the human CL cases. Also, positive association was demonstrated between ZCL in south and center of Setif Province and Meriones captured. Our finding, confirm that M. shawi is the principal reservoir host (76.78%) of the ZCL in Setif Province, since P. obesus was nearly absent (2.67%).

Spatiotemporal Variability of Zoonotic Cutaneous Leishmaniasis Based on Sociodemographic Heterogeneity. The Case of Northeastern Iran, 2011-2016.

Zoonotic cutaneous leishmaniasis (ZCL) is one of the most prevalent zoonoses in Iran, especially in central and northeastern Iran. This research aimed to examine whether there were spatiotemporal clusters of ZCL cases, and if so, whether there were differences in clustering according to age, sex, area of residence, and occupation. Spatial analysis, including global and local spatial autocorrelations, inverse distance weighting, and space-time scan statistics, were used to determine potential clusters in the villages of Golestan from 2011-2016. Several spatially significant (p < 0.05) clusters were observed in the north and northeastern regions, and most persisted until the last year of the study period. Children (0-10 years) living in rural settings were more likely to have an infection than those living in other areas. Although the disease was centered in the northern regions, housekeepers, females, and patients aged 21-30 and 41-50 years were found to be the high-risk groups in the southern areas. The seasonal pattern indicated that the outbreak mainly began in late summer, peaked in October, and diminished in December. By exploring spatiotemporal variations of ZCL by sociodemographic information, this study was able to identify priority areas for decision-makers in healthcare and resource allocation.

Innovative approach to control Zoonotic cutaneous leishmanisis: An Early warning system to predict ZCL outbreaks in Tunisia

Purpose: Tunisia is one of the most exposed countries to climate change. The increase in temperature and degree of moisture is a favorable condition for the development of vectors of several diseases. Thus, the zoonotic cutaneous leishmaniasis (ZCL), vector-borne disease highly sensitive to climatic conditions, has seen a dramatic resurgence in parts of the country as Sidi Bouzid, taking advantage of the warming in recent decades. The aim of this work was to build a regression model of ZCL cases to identify the relationship between ZCL occurrence and possible risk factors, and to develop a predicting model for ZCL's control and prevention purposes. Methods & Materials: We used monthly reported ZCL cases from an active surveillance system which was implemented in three rural areas. Bioclimatic variables were monthly data between July 2009 and June 2015, recorded from a private station implemented. We used a generalized additive model (GAM) and a generalized additive mixed model (GAMM) to assess the relation between ZCL incidence and climate factors (temperature, rainfall, relative humidity, wind speed and rodents’ density). Coefficients from the best fit model were used to predict monthly ZCL number for the next season and were compared to observed ones. Results: There were a total of 1019 notified ZCL cases from July 2009 to June 2015. The best-fit model showed significant associations between ZCL incidence and accumulated rainfall lagged 1 month, average temperature lagged 4 months, relative humidity with 4 months lag and rodent's density lagged 2 months. Prediction from GAMM approach gives a good prediction accuracy. The Pearson correlation coefficient value was 0.81. Conclusion: Understanding the role of the environmental and bioclimatic factors in ZCL occurrence can help to guide government policy-makers towards the creation and implementation of more effective policies to tackle the disease, and has important implications for prevention measures.

Immunity Against Leishmania major Infection: Parasite-Specific Granzyme B Induction as a Correlate of Protection

Zoonotic cutaneous leishmaniasis (ZCL) caused by Leishmania (L.) major infection is characterized by different clinical presentations which depend in part on the host factors. In attempt to investigate the impact of the host's immune response in the outcome of the disease, we conducted a prospective study of 453 individuals living in endemic foci of L. major transmission in Central Tunisia. Several factors were assessed at the baseline including (i) the presence of typical scars of ZCL, (ii) in vivo hypersensitivity reaction to leishmanin, and (iii) the in vitro release of granzyme B (Grz B) by peripheral blood mononuclear cells (PBMC) in response to stimulation with live L. major promastigotes. After one season of parasite's transmission, repeated clinical examinations allowed us to diagnose the new emerging ZCL cases. Heterogeneity was observed in terms of number of lesions developed by each individual as well as their size and spontaneous outcome, which led us to establish the parameter “severity of the disease.” The efficacy of the presence of typical ZCL scar, the leishmanin skin test (LST) positive reactivity and the high levels of Grz B (≥2 ng/ml), in the protection against the development of ZCL were 29, 15, and 22%, respectively. However, these factors were more efficient against development of intermediate or severe forms of ZCL. Levels of Grz B >2 ng/ml showed the best efficacy of protection (equals to 72.8%) against development of these forms of ZCL. The association of such parameter with the positivity of the LST exhibited a better efficacy (equals to 83.6%). In conclusion, our results support the involvement of Leishmania-specific cytotoxic cellular immune response in host protection against Leishmania-infection. This factor could be of great interest in monitoring the success of vaccination against human leishmaniasis.

Forecasting zoonotic cutaneous leishmaniasis using meteorological factors in eastern Fars province, Iran: a SARIMA analysis.

To predict the occurrence of zoonotic cutaneous leishmaniasis (ZCL) and evaluate the effect of climatic variables on disease incidence in the east of Fars province, Iran using the Seasonal Autoregressive Integrated Moving Average (SARIMA) model. The Box-Jenkins approach was applied to fit the SARIMA model for ZCL incidence from 2004 to 2015. Then the model was used to predict the number of ZCL cases for the year 2016. Finally, we assessed the relation of meteorological variables (rainfall, rainy days, temperature, hours of sunshine and relative humidity) with ZCL incidence. SARIMA(2,0,0) (2,1,0)12 was the preferred model for predicting ZCL incidence in the east of Fars province (validation Root Mean Square Error, RMSE = 0.27). It showed that ZCL incidence in a given month can be estimated by the number of cases occurring 1 and 2 months, as well as 12 and 24 months earlier. The predictive power of SARIMA models was improved by the inclusion of rainfall at a lag of 2 months (β = -0.02), rainy days at a lag of 2 months (β = -0.09) and relative humidity at a lag of 8 months (β = 0.13) as external regressors (P-values < 0.05). The latter was the best climatic variable for predicting ZCL cases (validation RMSE = 0.26). Time series models can be useful tools to predict the trend of ZCL in Fars province, Iran; thus, they can be used in the planning of public health programmes. Introducing meteorological variables into the models may improve their precision.

Risk Assessment of Zoonotic Cutaneous Leishmaniasis Cases among Manual Workers in Egypt

Risk Assessment of Zoonotic Cutaneous Leishmaniasis Cases among Manual Workers in Egypt

Modeling zoonotic cutaneous leishmaniasis incidence in central Tunisia from 2009-2015: Forecasting models using climate variables as predictors.

Transmission of zoonotic cutaneous leishmaniasis (ZCL) depends on the presence, density and distribution of Leishmania major rodent reservoir and the development of these rodents is known to have a significant dependence on environmental and climate factors. ZCL in Tunisia is one of the most common forms of leishmaniasis. The aim of this paper was to build a regression model of ZCL cases to identify the relationship between ZCL occurrence and possible risk factors, and to develop a predicting model for ZCL's control and prevention purposes. Monthly reported ZCL cases, environmental and bioclimatic data were collected over 6 years (2009–2015). Three rural areas in the governorate of Sidi Bouzid were selected as the study area. Cross-correlation analysis was used to identify the relevant lagged effects of possible risk factors, associated with ZCL cases. Non-parametric modeling techniques known as generalized additive model (GAM) and generalized additive mixed models (GAMM) were applied in this work. These techniques have the ability to approximate the relationship between the predictors (inputs) and the response variable (output), and express the relationship mathematically. The goodness-of-fit of the constructed model was determined by Generalized cross-validation (GCV) score and residual test. There were a total of 1019 notified ZCL cases from July 2009 to June 2015. The results showed seasonal distribution of reported ZCL cases from August to January. The model highlighted that rodent density, average temperature, cumulative rainfall and average relative humidity, with different time lags, all play role in sustaining and increasing the ZCL incidence. The GAMM model could be applied to predict the occurrence of ZCL in central Tunisia and could help for the establishment of an early warning system to control and prevent ZCL in central Tunisia.

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.

Identification and frequency distribution of Leishmania (L.) major infections in sand flies from a new endemic ZCL focus in southeast Iran

Zoonotic cutaneous leishmaniasis (ZCL) is an important public health challenge in Iran. It is often caused by the protozoan parasite, Leishmania major. This pathogen is principally transmitted by the infectious bites of adult female phlebotomine sand flies which belong to the subgenus Phlebotomus (Phlebotomus) Rondani and Berte (Diptera: Psychodidae). A recent outbreak of clinical ZCL cases in the rural district of Jask, Hormozgan province, southern Iran prompted the identification of sand flies naturally infected with L. major using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). A total of 8,123 wild sand flies were caught using sticky paper traps indoors and outdoors in seven villages of Jask from March 2007 to February 2008. About 120 trap-nights per month were carried out during peak seasonal density. Eight sand fly species of two distinct genera were morphologically identified. The most abundant species, Phlebotomus papatasi (≈60%) and Phlebotomus salehi (17%), had simultaneous population peaks in May and October. The anthropophilic index of P. papatasi was approximately twice that of P. salehi. PCR reactivity of L. major infections in P. salehi was weaker than those in P. papatasi. This is discussed with regard to their role in the natural transmission cycle of ZCL. This study provided the first PCR and ELISA evidence on P. salehi as a vector of L. major parasites in a new endemic region of ZCL in southeast Iran.

Molecular Detection of Leishmania major kDNA from Wild Rodents in a New Focus of Zoonotic Cutaneous Leishmaniasis in an Oriental Region of Iran

Human cutaneous leishmaniasis is one of the most challenging public health issues in many tropical and subtropical countries of the world, including Iran. More than half (54%) of the new zoonotic cutaneous leishmaniasis (ZCL) cases among the Eastern Mediterranean countries were reported from Iran in 2008. The detection of Leishmania parasites in rodents is essential to incriminate them as probable reservoir hosts of ZCL infection. As a result of the annual detection of about 200-250 clinical ZCL cases in the Jask district of southern Iran, feral rodents were trapped, identified to species level, and examined for Leishmania presence by preparing routine blood smears on microscopic slides from 2007 to 2008. Overall, 27 Tatera indica, 17 Gerbillus nanus, 29 Meriones persicus, 26 M. hurrianae, and 7 M. libycus were identified. Females of T. indica, M. hurrianae, and G. nanus appeared to be naturally infected with the protozoan parasite, L. major. This is the first report of microscopic and molecular detection of this trypanosomatid parasite infecting these three rodents reported from Hormozgan province in southeast Iran. More than three-quarters (82%) of the parasite-infected rodents came from the eastern plain of this province, but none of the other rodents were found to be smear-positive or kinetoplast DNA-positive by PCR. M. hurrianae, G. nanus, and T. indica are therefore incriminated as three potential reservoir hosts of L. major in Oriental parts of Iran.

Zoonotic cutaneous leishmaniasis in central Tunisia: spatio temporal dynamics

Zoonotic cutaneous leishmaniasis (ZCL) is endemic in many rural areas of the Southern and Eastern Mediterranean region where different transmission patterns of the disease have been described. This study was carried out in a region located in Central Tunisia and aimed to investigate the spatio-temporal dynamics of the disease from 1999 to 2004. Incident ZCL cases were defined by clinical diagnosis, confirmed by a positive skin test and/or parasitological examination. Annual ZCL rates were calculated for 94 regional sectors that comprise the study region of Sidi-Bouzid. Spatial and temporal homogeneity were initially investigated by chi-squared tests. Next, spatial scan statistics were used to identify spatial, temporal and spatio-temporal clusters that display abnormally high incidence rates. A hierarchical Bayesian Poisson regression model with spatial effects was fitted to signify explanatory socio-geographic factors related to spatial rate variability. Temporal ZCL dynamics for the 94 sectors were described via a linear mixed model. A total of 15 897 ZCL cases were reported in the 6-year study period, with an annual incidence rate of 669.7/100 000. An outbreak of the disease was detected in 2004 (1114/100 000). Spatial clustering is evident for the whole time period. The most likely cluster according to the spatial scan statistic, contains seven sectors with abnormally high incidence rates and approximately 5% of the total population. ZCL rates per sector are mostly related to the urban/rural index; sectoral population density and the number of inhabitants per household do not appear to contribute much to the explanation of rate variability. The dynamics of the disease within the study period are satisfactorily described by quadratic curves that differ for urban and rural areas. ZCL rates vary across space and time; rural/urban areas and environmental factors may explain part of this variation. In the study region, the Sidi Saâd dam-constructed in the early eighties and identified by previous studies as a major reason for the first outbreak of the disease-seems to be still related to increased ZCL rates. The most likely spatial cluster of high incidence rates contains regions located close to the dam. Our findings of increased incidences in urban areas support the hypothesis of increased incidences in peri-urban environments due to changes in sandfly/rodent living habits over recent years.

Zoonotic Cutaneous Leishmaniasis, Afghanistan

Zoonotic Cutaneous Leishmaniasis, Afghanistan