scholarly journals Molecular detection of Leishmania donovani, Leishmania major, and Trypanosoma spp. in Sergentomyia squamipleuris sandflies from a visceral leishmaniasis focus in Merti sub-County, eastern Kenya

2020 ◽  
Author(s):  
Barrack O. Owino ◽  
Jackline Milkah Mwangi ◽  
Steve Kiplagat ◽  
Hannah Njiriku Mwangi ◽  
Johnstone M. Ingonga ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Mus Musculus ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Control Measures ◽  
Health Concern ◽  
Coi Gene ◽  
Pcr Analysis ◽  
Mechanical Transmission ◽  
Reservoir Hosts

AbstractBackgroundVisceral leishmaniasis (VL) and zoonotic cutaneous leishmaniasis (ZCL) are of public health concern in Merti sub-County, Kenya, but epidemiological data on transmission, vector abundance, distribution, and reservoir hosts remains limited. To better understand the disease and inform control measures to reduce transmission, we investigated the abundance and distribution of sandfly species responsible for Leishmania transmission in the sub-County, and their blood-meal hosts.MethodsWe conducted an entomological survey in five villages with reported cases of VL in Merti sub-County, Kenya, using CDC miniature light traps and castor oil sticky papers. Sandflies were dissected and identified to the species level using standard taxonomic keys and PCR analysis of the cytochrome c oxidase subunit 1 (COI) gene. Leishmania parasites were detected and identified by PCR and sequencing of internal transcribed spacer 1 (ITS1) genes. Bloodmeal sources of engorged females were identified by high-resolution melting analysis of vertebrate cytochrome b (cyt-b) gene PCR products.ResultsWe sampled 526 sandflies consisting of eight species, Phlebotomus orientalis (1.52%; n = 8) and seven Sergentomyia spp. Sergentomyia squamipleuris was the most abundant sandfly species (78.71%; n = 414) followed by Sergentomyia clydei (10.46%; n = 55). Leishmania major, Leishmania donovani, and Trypanosoma DNA were detected in S. squamipleuris specimens. Humans were the main sources of sandfly bloodmeals. However, we also detected mixed bloodmeals; one S. squamipleuris specimen had fed on both human and mouse (Mus musculus) blood, while two Ph. orientalis specimens fed on human, hyrax (Procavia capensis), and mouse (Mus musculus) blood.ConclusionsOur findings implicate the potential involvement of S. squamipleuris in the transmission of Leishmania and question the dogma that human leishmaniases in the Old World are exclusively transmitted by sandflies of the Phlebotomus genus. The presence of Trypanosoma spp. may indicate mechanical transmission, whose efficiency should be investigated. Host preference analysis revealed the possibility of zoonotic transmission of leishmaniasis and other pathogens in the sub-County. Leishmania major causes ZCL while L. donovani is responsible for VL. However, the reservoir status of the parasites is not uniform. Further studies are needed to determine the reservoir hosts of Leishmania spp. in the area.

scholarly journals Molecular detection of Leishmania donovani, Leishmania major, and Trypanosoma species in Sergentomyia squamipleuris sand flies from a visceral leishmaniasis focus in Merti sub-County, eastern Kenya

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Barrack O. Owino ◽  
Jackline Milkah Mwangi ◽  
Steve Kiplagat ◽  
Hannah Njiriku Mwangi ◽  
Johnstone M. Ingonga ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Mus Musculus ◽  
Blood Meal ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Sand Fly ◽  
Health Concern ◽  
Sand Flies ◽  
Reservoir Hosts ◽  
Blood Meals

Abstract Background Visceral leishmaniasis (VL) and zoonotic cutaneous leishmaniasis (ZCL) are of public health concern in Merti sub-County, Kenya, but epidemiological data on transmission, vector abundance, distribution, and reservoir hosts remain limited. To better understand the disease and inform control measures to reduce transmission, we investigated the abundance and distribution of sand fly species responsible for Leishmania transmission in the sub-County and their blood-meal hosts. Methods We conducted an entomological survey in five villages with reported cases of VL in Merti sub-County, Kenya, using CDC miniature light traps and castor oil sticky papers. Sand flies were dissected and identified to the species level using standard taxonomic keys and PCR analysis of the cytochrome c oxidase subunit 1 (cox1) gene. Leishmania parasites were detected and identified by PCR and sequencing of internal transcribed spacer 1 (ITS1) genes. Blood-meal sources of engorged females were identified by high-resolution melting analysis of vertebrate cytochrome b (cyt-b) gene PCR products. Results We sampled 526 sand flies consisting of 8 species, Phlebotomus orientalis (1.52%; n = 8), and 7 Sergentomyia spp. Sergentomyia squamipleuris was the most abundant sand fly species (78.71%; n = 414) followed by Sergentomyia clydei (10.46%; n = 55). Leishmania major, Leishmania donovani, and Trypanosoma DNA were detected in S. squamipleuris specimens. Humans were the main sources of sand fly blood meals. However, we also detected mixed blood meals; one S. squamipleuris specimen had fed on both human and mouse (Mus musculus) blood, while two Ph. orientalis specimens fed on human, hyrax (Procavia capensis), and mouse (Mus musculus) blood. Conclusions Our findings implicate the potential involvement of S. squamipleuris in the transmission of Leishmania and question the dogma that human leishmaniases in the Old World are exclusively transmitted by sand flies of the Phlebotomus genus. The presence of Trypanosoma spp. may indicate mechanical transmission, whose efficiency should be investigated. Host preference analysis revealed the possibility of zoonotic transmission of leishmaniasis and other pathogens in the sub-County. Leishmania major and L. donovani are known to cause ZCL and VL, respectively. However, the reservoir status of the parasites is not uniform. Further studies are needed to determine the reservoir hosts of Leishmania spp. in the area.

scholarly journals Novel Arylimidamides for Treatment of Visceral Leishmaniasis

2010 ◽  
Vol 54 (6) ◽  
pp. 2507-2516 ◽  
Author(s):  
Michael Zhuo Wang ◽  
Xiaohua Zhu ◽  
Anuradha Srivastava ◽  
Qiang Liu ◽  
J. Mark Sweat ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Oral Treatment ◽  
Antileishmanial Activity ◽  
Repeat Dose ◽  
Lead Discovery ◽  
Preclinical Development

ABSTRACT Arylimidamides (AIAs) represent a new class of molecules that exhibit potent antileishmanial activity (50% inhibitory concentration [IC50], <1 μM) against both Leishmania donovani axenic amastigotes and intracellular Leishmania, the causative agent for human visceral leishmaniasis (VL). A systematic lead discovery program was employed to characterize in vitro and in vivo antileishmanial activities, pharmacokinetics, mutagenicities, and toxicities of two novel AIAs, DB745 and DB766. They were exceptionally active (IC50 ≤ 0.12 μM) against intracellular L. donovani, Leishmania amazonensis, and Leishmania major and did not exhibit mutagenicity in an Ames screen. DB745 and DB766, given orally, produced a dose-dependent inhibition of liver parasitemia in two efficacy models, L. donovani-infected mice and hamsters. Most notably, DB766 (100 mg/kg of body weight/day for 5 days) reduced liver parasitemia in mice and hamsters by 71% and 89%, respectively. Marked reduction of parasitemia in the spleen (79%) and bone marrow (92%) of hamsters was also observed. Furthermore, these compounds distributed to target tissues (liver and spleen) and had a moderate oral bioavailability (up to 25%), a large volume of distribution, and an elimination half-life ranging from 1 to 2 days in mice. In a repeat-dose toxicity study of mice, there was no indication of liver or kidney toxicity for DB766 from serum chemistries, although mild hepatic cell eosinophilia, hypertrophy, and fatty changes were noted. These results demonstrated that arylimidamides are a promising class of molecules that possess good antileishmanial activity and desirable pharmacokinetics and should be considered for further preclinical development as an oral treatment for VL.

scholarly journals Molecular and serological detection of Leishmania spp. in captive wild animals from Ilha Solteira, SP, Brazil

2011 ◽  
Vol 20 (3) ◽  
pp. 219-222 ◽  
Author(s):  
Márcia Mariza Gomes Jusi ◽  
Wilma Aparecida Starke-Buzetti ◽  
Trícia Maria Ferreira de Sousa Oliveira ◽  
Michely da Silva Tenório ◽  
Lúcio de Oliveira de Sousa ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Urban Areas ◽  
Leishmania Donovani ◽  
Complex Analysis ◽  
Fluorescent Antibody ◽  
Mammalian Species ◽  
Health Concern ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Animals ◽  
Leishmania Spp

Leishmaniasis is a zoonotic disease that affects 12 million people worldwide. Several mammalian species can serve as a reservoir for this disease. Dogs are the main reservoir for visceral leishmaniasis in urban areas, which has become a serious public health concern in Brazil. The aim of this study was to evaluate the presence of Leishmania spp. in captive wild animals from Ilha Solteira, São Paulo, Brazil. Blood and various tissues samples were collected from animals of five different species: Speothos venaticus, Chrysocyon brachyurus, Cerdocyon thous, Pseudalopex vetulus, and Procyon cancrivorus. Antibodies against Leishmania spp. were detected in three wild canids by indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). PCR analyses of blood and bone marrow from all animals were negative, but Leishmania DNA was found in the tissues and skin of seropositive animals. Positive PCR samples were also positive for Leishmania donovani complex. Analysis of sequenced PCR products showed similarities with different regions of Leishmania (Leishmania) infantum and Leishmania (Leishmania) chagasi kinetoplastids. Measures to control visceral leishmaniasis in wild animals kept in Brazilian zoos should be established, as no disease control programs are currently available.

scholarly journals Preclinical validation of a second generation leishmanization vaccine against vector transmitted fatal visceral leishmaniasis

2020 ◽  
Author(s):  
Subir Karmakar ◽  
Nevien Ismail ◽  
Fabiano Oliveira ◽  
James Oristian ◽  
Wen Wei Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Protective Efficacy ◽  
Sand Fly ◽  
Endemic Region ◽  
Cytokines And Chemokines ◽  
Human Leishmaniasis ◽  
Strong Candidate

AbstractVisceral Leishmaniasis (VL) is fatal if untreated. There is no licensed vaccine available against human leishmaniasis. We recently demonstrated protection in mice against L. major infection using a CRISPR genome edited attenuated Leishmania major strain (LmCen−/−). Here, as a pre-clinical step, we evaluated the protective efficacy of LmCen−/− against VL induced by sand fly transmitted Leishmania donovani in hamsters. Intradermal immunization of hamsters with LmCen−/− did not develop any lesion; while still priming a pro-inflammatory immune response. When challenged with L. donovani either by intradermal needle injection or by infected sand flies, LmCen−/−-immunized hamsters were protected, not showing spleen or liver pathology averting VL fatality compared to control animals. Spleen cells from LmCen−/− immunized and infected sand fly challenged hamsters produced significantly higher Th1-associated cytokines and chemokines including IFN-γ and TNF-α, and significantly reduced expression of the anti-inflammatory cytokines IL-10 and IL-21, compared to non-immunized challenged animals. We further developed a GLP-grade LmCen−/− which showed equal protection as laboratory-grade LmCen−/− parasites in hamsters. Importantly, GLP-grade LmCen−/− parasites also induced a proinflammatory immune response in the PBMCs isolated from healthy people living in non-endemic and endemic for VL as well as cured VL people living in endemic region. Together, this study demonstrates that the LmCen−/− parasites are safe and efficacious against VL and it is a strong candidate vaccine to be tested in a human clinical trial.

scholarly journals Outbreak of autochthonous canine visceral leishmaniasis in Santa Catarina, Brazil

2013 ◽  
Vol 33 (4) ◽  
pp. 490-496 ◽  
Author(s):  
Mário Steindel ◽  
Álvaro Menin ◽  
Tatiane Evangelista ◽  
Patrícia H. Stoco ◽  
Mariel A. Marlow ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Control Measures ◽  
Health Concern ◽  
Canine Visceral Leishmaniasis ◽  
Southern Brazil ◽  
Santa Catarina ◽  
Control Center ◽  
Spleen And Lymph Nodes ◽  
And Control ◽  
Autochthonous Transmission

The present study reports the first outbreak of autochthonous canine visceral leishmaniasis in Florianópolis, Santa Catarina, southern Brazil. Following the report of two cases of CVL, the Control Center of Zoonotic Diseases conducted a serological survey by ELISA and IFAT assays in seven districts of the Santa Catarina Island. Eleven seropositive dogs of autochthonous transmission were used in the present study. Infection by Leishmania sp. was confirmed by parasitological examination of bone marrow, liver, spleen and lymph nodes, culture in Schneider's medium and PCR. Leishmania sp. isolates were characterized by PCR-RFLP and hybridization with specific probes, allowing for the identification of Leishmania infantum. Autochthonous transmission of this disease in an area with high tourist traffic presents a major public health concern and signifies the emergence of an important zoonosis in southern Brazil. Therefore, the implementation of surveillance and control measures is imperative to prevent the spread of the disease among the canine population as well as transmission to the human population.

scholarly journals Preclinical validation of a live attenuated dermotropic Leishmania vaccine against vector transmitted fatal visceral leishmaniasis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Subir Karmakar ◽  
Nevien Ismail ◽  
Fabiano Oliveira ◽  
James Oristian ◽  
Wen Wei Zhang ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Intradermal Injection ◽  
Human Clinical Trial ◽  
Endemic Region ◽  
Tnf Α ◽  
Good Laboratory ◽  
Ifn Γ ◽  
Strong Candidate

AbstractVisceral Leishmaniasis (VL), a potentially fatal disease is caused by Leishmania donovani parasites with no vaccine available. Here we produced a dermotropic live attenuated centrin gene deleted Leishmania major (LmCen−/−) vaccine under Good Laboratory Practices and demonstrated that a single intradermal injection confers robust and durable protection against lethal VL transmitted naturally via bites of L. donovani-infected sand flies and prevents mortality. Surprisingly, immunogenicity characteristics of LmCen−/− parasites revealed activation of common immune pathways like L. major wild type parasites. Spleen cells from LmCen−/− immunized and L. donovani challenged hamsters produced significantly higher Th1-associated cytokines including IFN-γ, TNF-α, and reduced expression of the anti-inflammatory cytokines like IL-10, IL-21, compared to non-immunized challenged animals. PBMCs, isolated from healthy people from non-endemic region, upon LmCen−/− infection also induced more IFN-γ compared to IL-10, consistent with our immunogenicity data in LmCen−/− immunized hamsters. This study demonstrates that the LmCen−/− parasites are safe and efficacious against VL and is a strong candidate vaccine to be tested in a human clinical trial.

scholarly journals “Risk Factors for Visceral Leishmaniasis in Selected High Endemic Areas of Morang District, Nepal”: A case control study

2019 ◽  
Author(s):  
Punam Kumari Mandal ◽  
Rajendra Raj Wagle ◽  
Ajoy Kumar Thakur ◽  
Surendra Uranw
Keyword(s):  
Risk Factors ◽  
Socioeconomic Status ◽  
Visceral Leishmaniasis ◽  
Case Control Study ◽  
Health Sector ◽  
Case Control ◽  
Extensive Study ◽  
Control Measures ◽  
Health Concern ◽  
Control Study

AbstractVisceral leishmaniasis is a major public health concern in Nepal. During the last few years, several KA outbreaks have been reported from Tarai region including Morang district. A case control study was conducted to assess the risk factors associated with VL in 5 endemic VDC of Morang district with 62 cases already treated from BPKIHS and Koshi zonal hospital and 248 controls selected randomly from the same village. Data collected using semi structured questionnaire from September to November 2013. This study revealed that people living in thatched house, sleeping in ground floor, ownership of animal, history of migration to India (Bihar and Jharkhand) and proximity to other KA cases within 50 m distance of household were strong risk factors for VL. Education remains protective (OR 0.39,95 % CI 0.19-0.79). The association with socioeconomic status showed clear dose – response effect. The odds for VL consistently decreased as the level of socioeconomic status increased (OR 4.26, 3.81). Strengthening surveillance system for early diagnosis and treatment, awareness programme and further extensive study is needed on risk factor, vector and control measures.Author SummaryThis study aims to explore the risk factors for visceral leishmaniasis. Based on findings there is a need to educate people in high-transmission areas how to realize, reduce or avoid environmental factors that favor the survival of the vector in the community. Similarly introduction of more exact surveillance tools in order to improve morbidity and mortality surveillance by health sector. People living in mud thatched houses need to be aware about cracks and crevices in the mud walls, their function as breeding places and how they can be controlled, for example by plastering with lime and mud․. However, a primary condition is that people need to understand the purpose of all these efforts in order to be motivated to put them into practice.

scholarly journals Metagenomic Analysis Identifying a Rare Leishmania Infection in an Adult With AIDS

2021 ◽  
Vol 11 ◽  
Author(s):  
Pingping Song ◽  
Shuai Chen ◽  
Xiaoyu Tan ◽  
Yanjun Gao ◽  
Juanjuan Fu ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Health Concern ◽  
Leishmania Infection ◽  
Protozoan Parasites ◽  
Hiv Coinfection ◽  
Bone Marrow Specimen ◽  
And Control ◽  
Reservoir Hosts ◽  
Generation Sequencing

Leishmania belongs to a genus of the protozoan parasites that causes leishmaniasis, and includes cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). In this case, Leishmania amastigotes were found on cytomorphology examination of the bone marrow specimen, followed by 1,076 Leishmania donovani reads using metagenomic next generation sequencing (mNGS). Since being definitely diagnosed with VL/HIV coinfection, the patient was treated with liposomal amphotericin B as the parasite-resistant therapy and was discharged after clinical cure. But nearly a year later, on the mNGS follow-up, L. donovani was detected in the patient’s blood plasma specimen with 941 reads, suggesting that a relapse of leishmaniasis had occurred. These results indicate that leishmaniasis still exists in China and may represent a public health concern. This case could be helpful in the differential diagnosis of leishmaniasis, and for determining disease progression, prevention, and control of vectors and reservoir hosts.

scholarly journals The Egyptian mongoose,Herpestes ichneumon, is a possible reservoir host of visceral leishmaniasis in eastern Sudan

Parasitology ◽  
2001 ◽  
Vol 122 (5) ◽  
pp. 531-536 ◽  
Author(s):  
D. A. ELNAIEM ◽  
M. M. HASSAN ◽  
R. MAINGON ◽  
G. H. NURELDIN ◽  
A. M. MEKAWI ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Reservoir Host ◽  
Infection Rates ◽  
Sensitive Polymerase Chain Reaction ◽  
Polymerase Chain ◽  
Egyptian Mongoose ◽  
Herpestes Ichneumon ◽  
Reservoir Hosts ◽  
Eastern Sudan

Investigations were made on possible reservoir hosts ofLeishmania donovaniin 2 zoonotic foci of visceral leishmaniasis (VL) in Dinder National Park (DNP) and the peri-domestic habitats of adjacent villages of eastern Sudan. Animals were captured, in November 1997–1998 and April–May 1999 and examined forL. donovaniinfection using light microscopy and 2 sensitive Polymerase Chain Reaction (PCR) systems. Microscopy and PCR investigations were also used to determine the infection rates ofL. donovaniinPhlebotomus orientaliscaptured from the uninhabited site of DNP. Infections ofL. donovaniwere detected in 2 out of 14 Egyptian mongooses (Herpestes ichneumon), 1 out of 168Arviconthus niloticusand 1 out of 8Mastomys natalensis. Samples from 68 other animals captured from the study area were all negative for the infection. Active zoonotic transmission ofL. donovaniat the time of animal sampling in the uninhabited site of DNP was demonstrated by finding the parasite in 3.4% (7 out of 184) and 3.2% (5 out of 157) of flies collected in March 1998 and May 1999, respectively. We suggest that the Egyptian mongoose is a possible reservoir host ofL. donovani. The importance of other animals in maintaining the infection is also discussed.

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