Domestic dog ownership in Iran is a risk factor for human infection with Leishmania infantum.

One explanation proposed for the widespread failure to control zoonotic visceral leishmaniasis by culling infected domestic dogs is that wild canids or humans play significant roles in transmission. The aim of this study was to determine the importance of domestic dogs as the reservoir hosts of visceral leishmaniasis in northwest Iran. A random sample of 3,872 children and 199 dogs in 38 villages was surveyed by the direct agglutination test. Dog ownership details among these households were collected by questionnaire. Parasites isolated from 16 patients and 12 dogs were characterized as Leishmania infantum MON-1. Average seroprevalence in dogs (21.6%) was much higher than in children (7%). Child seropositivity increased significantly with village dog density in absolute terms (P < 0.001) and in relation to dog/human ratios (P = 0.028). Dog ownership within villages also was a significant risk factor for child seropositivity (P = 0.003)

Incidence and Disability-Adjusted Life Years (Dalys) Attributable to Leishmaniasis In Iran, 2013

Background: Leishmaniasis covers a range of clinical manifestations. Estimation of the burden of leishmaniasis may help guide healthcare management personnel and policy-makers in applying effective interventions. The present study aimed to calculate the incidence and burden of cutaneous and visceral leishmaniasis in Iran in 2013.Methods: To evaluate the epidemiological aspects of the disease in Iran, published studies over the past 20 years were searched and the viewpoints of relevant  specialists in Iran were obtained. Data were collected from the Ministry of Health and from the Tehran University of Medical Sciences. To calculate years of life lost due to premature death, standard expected years of life lost was used. Standard life table of Global Burden of Disease (GBD) 2010 with the life expectancy of 86.02 years for both sexes was used to calculate the remaining potential years of life at any age from death.Results: The overall incidence of cutaneous and visceral leishmaniasis was  calculated as 22 and 0.092 per 100000 population of Iran, respectively. The  burden of leishmaniasis was 99.5 years: 95.34 and 4.16 years for cutaneous and visceral, respectively. Sensitivity was analyzed and deaths predicted by the  Institute of Health Metrics and Evaluation added, the burden of visceral  leishmaniasis was 726 years.Conclusion: The share of leishmaniasis burden in Iran is lower than the global burden of the disease. GBD 2010 standard method is recommended to calculate the burden of leishmaniasis in different countries and set local priorities on the basis of these measures.Keywords: Incidence, Disability-adjusted life years, Cutaneous leishmaniasis, Visceral leishmaniasis, Ira

Unresponsiveness to Glucantime Treatment in Iranian Cutaneous Leishmaniasis due to Drug-Resistant Leishmania tropica Parasites

BACKGROUND: Recent circumstantial evidence suggests that an increasing number of Iranian patients with cutaneous leishmaniasis are unresponsive to meglumine antimoniate (Glucantime), the first line of treatment in Iran. This study was designed to determine whether the clinical responses (healing, or non-healing) were correlated with the susceptibility of Leishmania parasites to Glucantime. METHODS AND FINDINGS: In vitro susceptibility testing was first performed on 185 isolated parasites in the intracellular mouse peritoneal macrophage model. A strong correlation between the clinical outcome and the in vitro effective concentration 50% (EC (50)) values was observed. Parasites derived from patients with non-healing lesions had EC (50) values at least 4-fold higher than parasites derived from lesions of healing patients. A selection of these strains was typed at the molecular level by pulsed-field gels and by sequencing the pteridine reductase 1 (PTR1) gene. These techniques indicated that 28 out of 31 selected strains were Leishmania tropica and that three were Leishmania major. The L. major isolates were part of a distinct pulsed-field group, and the L. tropica isolates could be classified in three related additional pulsed-field groups. For each pulsed-field karyotype, we selected sensitive and resistant parasites in which we transfected the firefly luciferase marker to assess further the in vitro susceptibility of field isolates in the monocyte cell line THP1. These determinations confirmed unequivocally that patients with non-healing lesions were infected with L. tropica parasites resistant to Glucantime. Additional characterization of the resistant isolates showed that resistance is stable and can be reversed by buthionine sulfoximine, an inhibitor of glutathione biosynthesis. CONCLUSIONS: To the authors' knowledge, this is the first report of proven resistant parasites contributing to treatment failure for cutaneous leishmaniasis and shows that primary Glucantime-resistant L. tropica field isolates are now frequent in Iran

Iranian Native Plants on Treatment of Cutaneous Leishmaniosis: A Narrative Review

Background: Chemotherapy still relies on the use of pentavalent antimonials, amphotericin B, paromomycin, miltefosin, and allopurinol. In this study, we explained about the native plant that grows in different regions of Iran and used as anti-leishmanial in Iran and even many other countries. Methods: This narrative review covers all information about local herbal medicine in Iran that used in treatment of cutaneous leishmaniasis in all the worlds, published in local and international journals from 1996 to 2015 using various databases including PubMed, SID, Google Scholar, Scopus, and Science Direct. Results: Overall, 150 articles in databases were identified. Many local plants grown in some places of Iran were used to treat this endemic disease. Conclusion: The cutaneous leishmaniasis is also a major health problem in Iran, especially in Mashhad (Northeast of Iran). Therefore, many patients seek for herbal therapy that is cheaper and readily available. This review provides information regarding plant that exists in Iran and exhibiting effects on anti- Leishmania activity. Among the anti-leishmanial mentioned in this review, most have never been tested for cytotoxicity and very few have been tested for in vivo activity

Spironucleus muris and Eperythrozoon coccoides in Rodents from Northwestern Iran: Rare Infections

Background: Rodents perform a crucial role in dispersal of zoonosis causes globally. We aimed to investigation about infection levels of parasitic agents in rodents’ population in Meshkinshahr areas, northwest of Iran from Apr to Sep 2014. Methods: Two hundred four rodents were trapped and anaesthetized. A sample of blood was collected via cardi­opuncture from each one. Thin and thick blood smears were prepared and stained with Giemsa. All stained smear were examined under light microscopy with high magnification by two expert microscopists. Every suspected uni­cellular observed were measured microscopically and compared with key references to diagnose. Results: Captured rodents were identified as three genera including Meriones persicus, Mus musculus, Cricetulus migraturius. Protozoa identified in this study were included of Spironucleus muris and Eperythrozoon coccoides, these parasites were observed in blood smear of 0.98% of rodents. S. muris and E. coccoides were seen in M. mus­culus and C. migraturius, respectively. Conclusion: The present study increases awareness about Eperythrozoonosis in rodents and its potential transmis­sion to domestic animals and even to human in rural districts in Iran. Moreover, the attack of Spironucleus on the mucus of colon and its systemic risk was confirmed

Epidemiological aspects of canine visceral leishmaniosis in the Islamic Republic of Iran

An epidemiological study to examine the sero-prevalence of zoonotic visceral leishmaniosis (ZVL) among domestic and wild canines in endemic foci of Iran was carried out during 1999-2003 to assess the distribution of the disease and the possible association between infection in dogs, wild canines and people. Anti-leishmanial antibodies were detected by the direct agglutination test (DAT). Parasitological study was performed for all captured wild canines and were detected in some of the seropositive dogs with specific clinical signs (n = 107). Serum samples (n = 1568) were collected from domestic dogs in villages that are known endemic foci of human visceral leishmaniosis (HVL). Wild canine sera were collected from jackals (Canis aureus, n = 10), foxes (Vulpes vulpes, n = 10) and wolves (Canis lupus, n = 10). Of the 1568 serum sampled collected from domestic dogs, 222 (14.2%) were positive by DAT (1:320 and above). No statistically significant difference was found between male (15.2%) and female (11.8%) sero-prevalence (P = 0.083). Dogs of 8 years and above showed the highest sero-prevalence (40.6%). Only 23.9% of the seropositive domestic dogs had clinical signs. Parasitology and serology tests that were performed in 30 wild canines showed 10% these animals were infected by Leishmania infantum. Ten out of 11 Leishmania spp. isolated from the dogs and wild canines were identified as L infantum and one other as L. tropica by molecular and biochemical techniques. For the first time in Iran, L. infantum and L. tropica were isolated from viscera of both a wolf and a domestic dog. (c) 2005 Elsevier B.V. All rights reserved

Seroprevalence Survey of Visceral Leishmaniasis among Children up to 12 Years old and Domestic Dogs in Rural Areas of Dehloran District, Ilam Province of West Part of Iran, 2014

Background: Visceral leishmaniasis (VL), caused by Leishmania infantum (L. infantum), is a life-threatening vector-borne parasitic disease is distributed in some parts of the world. The disease is endemic in some parts of Iran. This study was aimed to determine the seroprevalence of VL among children and domestic dogs (as a reservoir of the parasite) in Dehloran, west of Iran.Materials and Methods: This cross-sectional study was carried out in Dehloran County. The blood samples of 872 children up to 12 years old and 52 dogs were collected from 10 villages of Dehloran using randomly-clustered sampling method. Sera were separated from all peripheral blood samples and tested by direct agglutination test (DAT). Anti-Leishmania infantum antibodies at titers of ≥1:800 and ≥1:80 were considered as Leishmania infantum infection in human and dog, respectively.Results: In general, among 872 human samples, 1.03% of samples had anti-Leishmania antibody with 1:1600 titers and 1.26% had 1:800 titers. In addition, from 52 dog samples, 21.15% of dogs had a titer of ≥1:320 and 25% had 1:80 and 1:160 titers.Conclusion: Our findings indicate that the seropositive dogs in the studied areas are considerable and L. infantum may be circulated between human and domestic dog in the studied area. Further study of isolation and molecular identification of Leishmania spp. is recommended

IgG Avidity ELISA Test for Diagnosis of Acute Toxoplasmosis in Humans

Serum samples, 100 in the total number, were collected from different laboratories in Tehran, Iran and tested for anti-Toxoplasma specific IgG and IgM antibodies using indirect immunofluorescent antibody test (IFAT). Using the IgG (chronic) and IgM (acute) positive samples, the IgG avidity test was performed by ELISA in duplicate rows of 96-well microtiter plates. One row was washed with 6 M urea and the other with PBS (pH 7.2), then the avidity index (AI) was calculated. Sixteen out of 18 (88.9%) sera with acute toxoplasmosis showed low avidity levels (AI≤50), and 76 out of 82 (92.7%) sera in chronic phase of infection showed high avidity index (AI>60). Six sera had borderline ranges of AI. The results showed that the IgG avidity test by ELISA could distinguish the acute and chronic stages of toxoplasmosis in humans

Inhibition of pteridine reductase 1 (PTR1) expression in Leishmania promastigotes using a full-length antisense construct

Leishmania exhibit many unusual features, one of which is the pteridine metabolic pathway essential for the growth for these parasites. Leishmania have evolved a complex and versatile pteridine salvage network capable of scavenging a wide array of conjugated and unconjugated pteridines. The L. major PTR1 gene was cloned into pcDNA3 digested with KpnI and BamHI. The gene was cloned antiparallel to the promoter and named pcDNA-Rptr. L. major promastigotes were divided into two groups. One group was transfected with 50 &#x3bc;g of pcDNA-Rptr, whereas the other group was electroporated with pcDNA3. Mentioned cells were cultured and plated onto semi-solid media.Western blotting was performed on extracts from transfected promastigotes of L. major using an leishmania major PTR1 antibody. The PTR1 protein was not expressed in pcDNA-Rptr-tansfected promastigotes, &#x27;Our results indicate that our system may be useful for studying the pteridine salvage pathway in Leishmania as a possible drug target

Molecular Identification and Intra-species Variations among Leishmania infantum Isolated from Human and Canine Visceral Leishmaniasis in Iran

Background: In Iran, both forms of cutaneous (CL) and visceral leishmaniasis (VL) have been re-ported; so the accurate species identification of the parasite(s) and the analysis of genetic diversity are necessary. Methods: The investigation was conducted from 2014 to 2015 in the northwest and south of Iran, where VL is endemic (7 provinces). Blood samples of patients and infected dogs were collected and sera separated for serologic examinations (DAT, rK39). Spleen or bone marrow samples from infected dogs were also collected to confirm the infection. DNAs of 70 samples amplified by targeting a partial sequence of ITS (18S rRNA–ITS1–5.8S rRNA–ITS2) gene. All the amplicons were sequenced and analyzed with restriction fragment length polymorphism (RFLP) using the TaqI enzyme. Results: The cause of all 70 VL cases, were L. infantum, so, the dominant specie is L. infantum. The sequencing results of all VL cases and RFLP analysis corroborate each other. Discrimination of Iranian Leishmania isolates using ITS gene gives us this opportunity to detect, identify and construct the phylogenetic relationship of Iranian isolates. In addition, detection and differentiation of Leishmania spp. DNA was confirmed by amplification of variable area of the minicircle kDNA (conserved sequence blocks (CSB)). Conclusion: Low divergence and high likelihood were seen among L. infantum isolates of human and dogs from Iran with a very slight divergence was seen between isolates from northwest and south of Iran, thus grouped in a unique clad. No correlation was observed between intraspecies divergence and geographic distribution of the isolates