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1.
Parasitol Res ; 123(10): 346, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39384662

ABSTRACT

The European badger (Meles meles) is a common mustelid species known as a significant reservoir for various human and animal diseases. Studies investigating Leishmania infection in European badgers across Mediterranean regions have yielded inconsistent findings. In Spain, results are particularly controversial: some studies confirm the presence of Leishmania in badgers, while others do not. Our study aimed to conduct a retrospective histopathological and immunohistochemical analysis to detect Leishmania in tissues of nine European badgers from northeastern Spain, a region previously unevaluated for Leishmania infection in this species. Microscopic examination revealed lesions indicative of leishmaniosis in the lymph nodes and spleens of six badgers. In one of them, Leishmania-like structures were identified in multiple organs and confirmed via immunohistochemistry. Parasites were detected in the lymph nodes, spleen, adrenal glands, and pancreas. The parasite load was high in the adrenal glands, moderate in the lymph nodes and spleen, and low in the pancreas. No parasites were found in other examined organs. This finding represents a frequency of 11.11% (1/9) of Leishmania infection among the badgers we studied. Further investigation of wildlife and atypical reservoirs can enhance our understanding of the pathogenesis of this significant zoonotic disease.


Subject(s)
Immunohistochemistry , Leishmania infantum , Leishmaniasis, Visceral , Mustelidae , Spleen , Animals , Mustelidae/parasitology , Leishmania infantum/isolation & purification , Spain , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/veterinary , Leishmaniasis, Visceral/pathology , Spleen/parasitology , Spleen/pathology , Lymph Nodes/parasitology , Lymph Nodes/pathology , Female , Retrospective Studies , Male , Parasite Load , Disease Reservoirs/parasitology
2.
BMC Vet Res ; 20(1): 448, 2024 Oct 04.
Article in English | MEDLINE | ID: mdl-39363300

ABSTRACT

BACKGROUND: Dogs may be infected with species of Leishmania parasites that are disseminated through blood circulation and invade the internal organs. In this study, we aim to detect the parasite in the blood of dogs using the PCR technique. The present work was performed from February 2022 to May 2023 in Fars Province, southern Iran, where the disease is endemic. RESULTS: In total, 7(5.1%) out of 135 blood samples, six were identified as Leishmania tropica and one as Leishmania major. We found no trace of Leishmania infantum, which is always known for visceral infection. In addition, no sign of cutaneous lesions or a significant disease was seen in the animals infected with both species. Of 48 dogs with anemia, two were Leishmania positive. The mean value of hematological parameters in the infected dogs was within the normal range except for a significant reduction in the platelet measures (p < 0.05). CONCLUSIONS: Our data revealed that both Leishmania species, tropica and major, may manifest as viscerotropic leishmaniasis. More investigations are needed to understand the conditions under which these species choose the type of infection. Moreover, our data emphasize the role of asymptomatic dogs in carrying these parasites, a crucial factor in spreading the disease.


Subject(s)
Dog Diseases , Leishmania major , Leishmania tropica , Animals , Leishmania tropica/isolation & purification , Dogs , Dog Diseases/parasitology , Dog Diseases/blood , Leishmania major/isolation & purification , Iran/epidemiology , Male , Female , Polymerase Chain Reaction/veterinary , Leishmaniasis, Cutaneous/veterinary , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Cutaneous/blood , Leishmaniasis, Visceral/veterinary , Leishmaniasis, Visceral/blood , Leishmaniasis, Visceral/parasitology
3.
PLoS One ; 19(10): e0311314, 2024.
Article in English | MEDLINE | ID: mdl-39365771

ABSTRACT

Visceral Leishmaniasis (VL) is a deadly, vector-borne, parasitic, neglected tropical disease, particularly prevalent on the Indian subcontinent. Sleeping under the long-lasting insecticide-treated nets (ITNs) was considered an effective VL prevention and control measures, until KalaNet, a large trial in Nepal and India, did not show enough supporting evidence. In this paper, we adapt a biologically accurate, yet relatively simple compartmental ordinary differential equations (ODE) model of VL transmission and explicitly model the use of ITNs and their role in VL prevention and elimination. We also include a game-theoretic analysis in order to determine an optimal use of ITNs from the individuals' perspective. In agreement with the previous more detailed and complex model, we show that the ITNs coverage amongst the susceptible population has to be unrealistically high (over 96%) in order for VL to be eliminated. However, we also show that if the whole population, including symptomatic and asymptomatic VL cases adopt about 90% ITN usage, then VL can be eliminated. Our model also suggests that ITN usage should be accompanied with other interventions such as vector control.


Subject(s)
Insecticide-Treated Bednets , Leishmaniasis, Visceral , Leishmaniasis, Visceral/prevention & control , Leishmaniasis, Visceral/transmission , Leishmaniasis, Visceral/epidemiology , Humans , India/epidemiology , Insecticide-Treated Bednets/statistics & numerical data , Models, Theoretical , Animals , Nepal/epidemiology
4.
Parasite Immunol ; 46(10): e13063, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39360782

ABSTRACT

Interleukin 27 (IL-27) is a cytokine that regulates susceptibility to Leishmania infantum infection in humans and experimental models. This cytokine has not yet been described in canine leishmaniasis (CanL). Therefore, we investigated whether IL-27 has a regulatory role in CanL. The EBI3 and p28 subunits of IL-27 were measured in splenic leukocytes culture supernatant from dogs with CanL and compared to control dogs. We also correlated EBI3 and p28 levels with IL-21, anti-L. infantum antibodies and parasite loads. We performed functional assays followed by IL-27 blockade and measured parasite loads, production of cytokines in splenic leukocytes culture supernatant, and the expression of PD-1, CTLA-4, phospho-Stat-1/3, T-bet, GATA3 and nitric oxide production (NO). Both IL-27 subunits increased in the supernatant of dogs with CanL compared to control dogs. EBI3 and p28 levels showed a moderate positive correlation with IL-21 (r = 0.67, p < 0.0001 and r = 0.45, p < 0.012, respectively), and the EBI3 subunit was positively associated with anti-L. infantum IgG antibodies (r = 0.38, p < 0.040) and parasite load (r = 0.47, p < 0.009). IL-27 and IL-21 participate of immune responses in CanL. IL-27 may be associated with the failure of immunity to control parasite replication via upregulation of the expression of PD-1, CTLA-4, T-bet and NO in splenic leukocytes from dogs with CanL. These findings suggest that the pathways regulated by IL-27 are involved in CanL pathogenesis in the host, and may be targets for new therapies.


Subject(s)
Dog Diseases , Interleukin-27 , Leishmania infantum , Leishmaniasis, Visceral , Parasite Load , Animals , Dogs , Dog Diseases/immunology , Dog Diseases/parasitology , Leishmania infantum/immunology , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/veterinary , Leishmaniasis, Visceral/parasitology , Interleukin-27/metabolism , Adaptive Immunity , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Male , Spleen/immunology , Spleen/parasitology , Interleukins/metabolism , Interleukins/immunology , Female , Cytokines/metabolism , Leukocytes/immunology , Leukocytes/parasitology
5.
Front Immunol ; 15: 1402539, 2024.
Article in English | MEDLINE | ID: mdl-39359727

ABSTRACT

L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates. Clinical manifestations such as post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis-mimic (VL-associated HLH-mimic) further contribute to the diversity of clinical manifestations. These clinical variations are intricately influenced by the complex interplay between the host's immune response and the parasite's escape mechanisms. This narrative review aims to elucidate the underlying immunological mechanisms associated with each clinical manifestation, drawing from published literature within the last 5 years. Specific attention is directed toward viscerotropic Leishmania sinfection in patients with inborn errors of immunity and acquired immunodeficiencies. In VL, parasites exploit various immune evasion mechanisms, including immune checkpoints, leading to a predominantly anti-inflammatory environment that favors parasite survival. Conversely, nearly 70% of individuals are capable of mounting an effective pro-inflammatory immune response, forming granulomas that contain the parasites. Despite this, some patients may experience reactivation of the disease upon immunosuppression, challenging current understandings of parasite eradication. Individuals living with HIV and those with inborn errors of immunity present a more severe course of infection, often with higher relapse rates. Therefore, it is crucial to exclude both primary and acquired immune deficiencies in patients presenting disease relapse and VL-associated HLH-mimic. The distinction between VL and HLH can be challenging due to clinical similarities, suggesting that the nosological entity known as VL-associated HLH may represent a severe presentation of symptomatic VL and it should be considered more accurate referring to this condition as VL-associated HLH-mimic. Consequently, excluding VL in patients presenting with HLH is essential, as appropriate antimicrobial therapy can reverse immune dysregulation. A comprehensive understanding of the immune-host interaction underlying Leishmania infection is crucial for formulating effective treatment and preventive strategies to mitigate the disease burden.


Subject(s)
Leishmaniasis, Visceral , Humans , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Animals , Host-Parasite Interactions/immunology , Leishmania donovani/immunology , Leishmania infantum/immunology , Leishmania/immunology
6.
Molecules ; 29(17)2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39274889

ABSTRACT

Leishmania infantum is the vector-borne trypanosomatid parasite causing visceral leishmaniasis in the Mediterranean basin. This neglected tropical disease is treated with a limited number of obsolete drugs that are not exempt from adverse effects and whose overuse has promoted the emergence of resistant pathogens. In the search for novel antitrypanosomatid molecules that help overcome these drawbacks, drug repurposing has emerged as a good strategy. Nitroaromatic compounds have been found in drug discovery campaigns as promising antileishmanial molecules. Fexinidazole (recently introduced for the treatment of stages 1 and 2 of African trypanosomiasis), and pretomanid, which share the nitroimidazole nitroaromatic structure, have provided antileishmanial activity in different studies. In this work, we have tested the in vitro efficacy of these two nitroimidazoles to validate our 384-well high-throughput screening (HTS) platform consisting of L. infantum parasites emitting the near-infrared fluorescent protein (iRFP) as a biomarker of cell viability. These molecules showed good efficacy in both axenic and intramacrophage amastigotes and were poorly cytotoxic in RAW 264.7 and HepG2 cultures. Fexinidazole and pretomanid induced the production of ROS in axenic amastigotes but were not able to inhibit trypanothione reductase (TryR), thus suggesting that these compounds may target thiol metabolism through a different mechanism of action.


Subject(s)
Leishmania infantum , Nitroimidazoles , Leishmania infantum/drug effects , Leishmania infantum/metabolism , Nitroimidazoles/pharmacology , Nitroimidazoles/chemistry , Animals , Mice , Humans , RAW 264.7 Cells , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Free Radicals/metabolism , Hep G2 Cells , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/drug therapy , Cell Death/drug effects , Reactive Oxygen Species/metabolism , Cell Survival/drug effects , High-Throughput Screening Assays , NADH, NADPH Oxidoreductases
7.
Trop Med Int Health ; 29(10): 904-912, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39229674

ABSTRACT

BACKGROUND: Visceral leishmaniasis (VL) is a severe parasitic disease transmitted by phlebotomine sandflies. VL is endemic in West Pokot County, Kenya, where effective strategies to interrupt transmission are impeded by the limited understanding of VL risk factors. Therefore, this case-control study aimed to explore environmental, behavioural and household determinants of VL in West Pokot. METHODS: From November 2022 to January 2023, a structured questionnaire was administered to 36 symptomatic primary VL cases attending Kacheliba Sub-County Hospital in West Pokot and to 50 healthy controls from local villages. The VL status of all participants was confirmed using an rK39 rapid diagnostic test. Associations between questioned determinants and VL were investigated by means of age-corrected univariate logistic regression analysis. RESULTS: Significant associations were found between VL and housing characteristics, such as window presence and floor type. VL cases more frequently reported the presence of cattle, dogs and sheep in their house yards. VL was also associated with cutting down trees in the house yard and house proximity to several Acacia tree species. Furthermore, outdoor activities, including travelling outside the residence for more than 2 weeks, activities near termite mounds, and forest activities during the rainy season, increased the risk of VL. CONCLUSIONS: This work reports a number of previously undescribed risk factors for VL in the understudied West Pokot focus. The results suggest VL transmission occurs both peri-domestically at night and outdoors during the day, particularly when sandfly resting sites are disturbed. Our findings warrant further research into sandfly ecology and potential zoonotic parasite reservoirs in West Pokot.


Subject(s)
Leishmaniasis, Visceral , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/transmission , Humans , Kenya/epidemiology , Case-Control Studies , Risk Factors , Male , Female , Adult , Animals , Child , Adolescent , Young Adult , Child, Preschool , Middle Aged , Dogs , Housing , Surveys and Questionnaires
8.
Cell Rep ; 43(9): 114720, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39244752

ABSTRACT

Macrophages are major host cells for the protozoan Leishmania parasite. Depending on their activation state, they either contribute to the detection and elimination of Leishmania spp. or promote parasite resilience. Here, we report that the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of the NOX2/reactive oxygen species (ROS) axis in early Nrf2 activation and, subsequently, prostaglandin E2 (PGE2)/EP2r signaling in the sustenance of Nrf2 activation upon infection. Moreover, we establish a ferroptosis-like process within macrophages as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of L. infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of therapeutic approaches for the treatment of visceral leishmaniasis.


Subject(s)
Ferroptosis , Leishmania infantum , Leishmaniasis, Visceral , Macrophages , NF-E2-Related Factor 2 , Reactive Oxygen Species , NF-E2-Related Factor 2/metabolism , Macrophages/metabolism , Macrophages/parasitology , Animals , Mice , Reactive Oxygen Species/metabolism , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/metabolism , Leishmaniasis, Visceral/pathology , Signal Transduction , Cell Death , NADPH Oxidase 2/metabolism , NADPH Oxidase 2/genetics , Humans , Mice, Inbred C57BL , Dinoprostone/metabolism , Female
9.
PLoS Negl Trop Dis ; 18(9): e0012000, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39348450

ABSTRACT

Human immunodeficiency virus (HIV) co-infection is a major challenge for visceral leishmaniasis (VL) control, particularly in Ethiopia where the incidence of both pathogens is high. VL-HIV often leads to high rates of antileishmanial treatment failure and recurrent VL disease relapses. Considering the high prevalence of HIV and Leishmania in the Ethiopian population, preventing the progression of asymptomatic Leishmania infection to disease would be a valuable asset to VL disease control and to the clinical management of people living with HIV (PLWH). However, such a strategy requires good understanding of risk factors for VL development. In immunocompetent individuals living in Brazil, India, or Iran, the Human Leukocyte Antigen (HLA) gene region has been associated with VL development. We used NanoTYPE, an Oxford Nanopore Technologies sequencing-based HLA genotyping method, to detect associations between HLA genotype and VL development by comparing 78 PLWH with VL history and 46 PLWH that controlled a Leishmania infection, all living in a VL endemic region of North-West Ethiopia. We identified an association between HLA-A*03:01 and increased risk of VL development (OR = 3.89). These data provide candidate HLA alleles that can be further explored for inclusion in a potential Leishmania screen-and-treat strategy in VL endemic regions.


Subject(s)
Coinfection , HIV Infections , Leishmaniasis, Visceral , Leishmaniasis, Visceral/epidemiology , Humans , Ethiopia/epidemiology , HIV Infections/complications , HIV Infections/epidemiology , Male , Adult , Female , Coinfection/epidemiology , Genotype , Young Adult , Middle Aged , HLA-A Antigens/genetics , Adolescent , Alleles , Genetic Predisposition to Disease
10.
Parasitology ; 151(7): 753-761, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39311405

ABSTRACT

Visceral leishmaniasis (VL) is a severe infectious disease caused by protozoan parasites of the Leishmania donovani complex. Blood cytokine concentrations in VL patients can inform us about underlying immunopathogenesis and may serve as a biomarker for treatment effectiveness. However, cytokine levels have not yet been studied in VL patients from Kenya, where case load is high. This study measured the serum cytokine profile, blood parasite load and clinical and haematological features of VL patients from West Pokot County, Kenya, over the course of treatment with sodium stibogluconate and paromomycin (SSG-PM). VL patients recruited at the hospital presented with splenomegaly and weight loss, and frequently had pancytopenia and anaemia. Median Leishmania parasite load in blood, determined with real-time polymerase chain reaction, was 2.6 × 104 parasite equivalents mL−1. Compared to endemic healthy controls, serum interferon gamma (IFN-γ), interleukin 5 (IL-5), IL-6, IL-10, IL-12p70, IL-17A and IL-27 were significantly elevated in untreated VL patients. Severe VL was associated with higher IL-10 and lower IFN-γ levels. After 17 daily injections with SSG-PM, disease symptoms disappeared, leukocyte and thrombocyte counts significantly increased, and blood parasite load decreased to undetectable levels in all VL patients. There was a significant decrease in IL-10 and IL-6, whereas IL-17A levels increased; the remaining cytokines showed no significant concentration change during treatment. In conclusion, the results suggest that SSG-PM treatment of VL patients from West Pokot was effective. Moreover, both inflammatory and regulatory immune responses appeared to decrease during treatment, although the increase in IL-17A could reflect a partial continuation of immune activation.


Subject(s)
Antimony Sodium Gluconate , Antiprotozoal Agents , Cytokines , Leishmania donovani , Leishmaniasis, Visceral , Parasite Load , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/blood , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/epidemiology , Humans , Cytokines/blood , Kenya/epidemiology , Male , Female , Adult , Antimony Sodium Gluconate/therapeutic use , Adolescent , Leishmania donovani/immunology , Leishmania donovani/physiology , Antiprotozoal Agents/therapeutic use , Child , Young Adult , Paromomycin/therapeutic use , Child, Preschool , Middle Aged
11.
PLoS Negl Trop Dis ; 18(9): e0012500, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39325693

ABSTRACT

Visceral leishmaniasis (VL) is a severe and potentially fatal infection, with over 90% of reported cases occurring in East African countries including Chad, Djibouti, Eritrea, Ethiopia, Kenya, Somalia, South Sudan, Sudan, and Uganda, affecting mainly impoverished individuals, and creating a significant economic burden. Currently, the intravenous single-dose liposomal amphotericin B is the first choice for the treatment of VL. Recently, WHO and DNDi have suggested a combination of intravenous liposomal amphotericin B and oral miltefosine as a potential approach to treat VL. However, miltefosine availability is uncertain, and its side effects frequently cause treatment to be discontinued. Furthermore, due to the difficult route of liposomal amphotericin B administration by intravenous infusion, the lack of formulation's tropical stability, accessibility, injection toxicity, and cost have prevented this injectable formulation of amphotericin B from reaching the most infected populations, particularly the pediatric population. To solve this problem, the development of a solid oral amphotericin B formulation that is cost-effective, safe, tropically stable, and easy to swallow, making it more accessible to children, particularly in rural communities having limited access to medical clinics or trained healthcare professionals is imperative. This viewpoint will discuss the opportunities and challenges of developing an oral amphotericin B formulation for a pediatric population.


Subject(s)
Amphotericin B , Antiprotozoal Agents , Leishmaniasis, Visceral , Amphotericin B/administration & dosage , Amphotericin B/adverse effects , Humans , Leishmaniasis, Visceral/drug therapy , Administration, Oral , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/adverse effects , Child , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/administration & dosage , Phosphorylcholine/adverse effects , Phosphorylcholine/therapeutic use , Child, Preschool , Africa, Eastern
12.
Vet Parasitol ; 331: 110299, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39232468

ABSTRACT

Canine Visceral Leishmaniasis (CVL) is the most fatal form of Leishmania infection in dogs and is caused by L. infantum in the Americas. This parasite follows a zoonotic life cycle, raising concerns within domestic households, where dogs act as the primary reservoir of the parasite. Accurately detecting infected dogs is vital for effective epidemiological control in both canine and human populations. However, existing diagnostic methods in Brazil have limitations, particularly in detecting asymptomatic and oligosymptomatic dogs, leading to ineffective disease control. To address this challenge, we evaluated a novel recombinant antigen from L. infantum, the rLiNTPDase2. Previous studies have confirmed its high performance via ELISA, leading us to assess its suitability for a Lateral Flow Immunochromatographic Assay (LFIA), which is ideal for point-of-care testing. Standardization of the assay involved testing two nitrocellulose membranes (HF135 and HF120, Millipore), three blocking protocols, and five sample dilutions (1:10, 1:20, 1:40, 1:80, and 1:160). Following the chosen conditions (HF120 membrane, 1-minute blocking protocol, and 1:80 sample dilution), we validated our assay with a sample size of 78 dogs, comprising 32 negatives and 46 positives, including symptomatic (n=23), oligosymptomatic (n=17), and asymptomatic (n=6) cases. The results revealed a sensitivity of 86.9 %, specificity of 62.5 %, and accuracy of 76.9 %, which is consistent with ELISA performance for the same samples. Compared to DPP-LVC, our assay demonstrated promising results in detecting asymptomatic and oligosymptomatic cases. This study underscores the suitability of the rLiNTPDase2 antigen for the LFIA format, suggesting its potential as a novel point-of-care diagnostic test for CVL.


Subject(s)
Antigens, Protozoan , Dog Diseases , Leishmaniasis, Visceral , Sensitivity and Specificity , Animals , Dogs , Leishmaniasis, Visceral/veterinary , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/parasitology , Dog Diseases/diagnosis , Dog Diseases/parasitology , Antigens, Protozoan/immunology , Antigens, Protozoan/analysis , Chromatography, Affinity/veterinary , Chromatography, Affinity/methods , Leishmania infantum/enzymology , Leishmania infantum/immunology , Recombinant Proteins/immunology , Enzyme-Linked Immunosorbent Assay/veterinary , Enzyme-Linked Immunosorbent Assay/methods
13.
Parasite Immunol ; 46(8-9): e13066, 2024.
Article in English | MEDLINE | ID: mdl-39310969

ABSTRACT

Obligate intracellular protozoan parasite, Leishmania donovani, causative agent of visceral leishmaniasis, led to impaired macrophage functions. It is well documented that many of these changes were induced by parasite-mediated reduction in macrophage cholesterol content. Leishmania-mediated alteration in the other lipids has not been explored in detail yet. Here, we found that the expression of key cholesterol biosynthetic genes and total cellular cholesterol were reduced during L. donovani infection. Further, we have also identified that this reduction in the cholesterol led to increased membrane fluidity and inhibition of antigen-presenting potential of macrophages. In addition to this, we studied the relative changes in different lipids in THP-1-derived macrophages during L. donovani infection through liquid chromatography-mass spectrometry. We found that Sphingomyelin (16:0) and ceramide (20:1, 26:0 and 26:1) were significantly reduced in infected macrophages. We further observed that the majority of different sub-classes of phospholipids were downregulated significantly. Overall ratio of phosphatidylcholine versus phosphotidylethanolamine was decreased which indicated the compensatory mechanism of cell in response to cholesterol reduction. The observed Leishmania-mediated alteration in macrophage-lipidome provided the novel insights into mechanism of host-pathogen interactions.


Subject(s)
Cholesterol , Leishmania donovani , Leishmaniasis, Visceral , Lipidomics , Macrophages , Leishmania donovani/immunology , Macrophages/immunology , Macrophages/parasitology , Macrophages/metabolism , Humans , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/metabolism , Cholesterol/metabolism , THP-1 Cells , Host-Pathogen Interactions/immunology , Lipid Metabolism , Membrane Fluidity
14.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(4): 329-333, 2024 Aug 28.
Article in Chinese | MEDLINE | ID: mdl-39322290

ABSTRACT

Leishmaniasis is a zoonotic parasitic disease caused by Leishmania infection and transmitted by sandflies. There are three main forms of leishmaniasis, including cutaneous leishmaniasis, visceral leishmaniasis and mucocutaneous leishmaniasis. China is mainly endemic for visceral leishmaniasis, which is a class C notifiable infectious disease in the country. Following concerted efforts, the transmission of visceral leishmaniasis had been controlled in most endemic foci of China by the end of 1958, with a few cases reported in western China. Due to global climate changes and population mobility, resurgence of visceral leishmaniasis has recently occurred in historical endemic areas of central and western China, which is characterized by gradual expansion of endemic areas and remarkable rebounding epidemics. Hereby, we summarize the national and global epidemiology and control strategy of visceral leishmaniasis, propose 8 key research areas and 12 key research topics for visceral leishmaniasis control, and recommend the establishment of the joint prevention and control mechanism of "human-animals-vectors" and the working mechanism of animal prevention for human diseases based on the One Health approach, so as to combat the resurgence of visceral leishmaniasis in China.


Subject(s)
Leishmaniasis, Visceral , Leishmaniasis, Visceral/prevention & control , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/transmission , China/epidemiology , Humans , Animals , Research/trends
15.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(4): 346-351, 2024 Jul 30.
Article in Chinese | MEDLINE | ID: mdl-39322293

ABSTRACT

OBJECTIVE: To investigate the geographical distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Henan Province in 2023, so as to provide insights into the prevention and control of visceral leishmaniasis vectors. METHODS: A total of 23 counties (districts) were sampled from 18 cities of Henan Province from May to September, 2023 as sandfly surveillance sites, and sandflies were captured using human capture and light trapping methods. Following morphological identification, the changes in the sandfly density were calculated at different months and in different breeding habitats. RESULTS: A total of 406 light traps were set at sandfly surveillance sites in Henan Province from May to September, 2023, and a total of 3 137 female sandlies were captured, with an average density of 7.73 sandlies/(light·night). A total of 1 494 Phlebotomus chinensis sandflies were captured, including 1 222 female sandflies, with an average density of 3.01 sandflies/(light·night), and the highest density of P. chinensis was found in Gongyi City [17.00 sandflies/(light·night)]. A total of 5 544 sandflies were captured using the human capture method, including 230 P. chinensis, and the density of P. chinensis appeared a unimodal distribution, with a peak in early July [5.81 sandflies/(light·night)]. Among different breeding habitats, the highest P. chinensis density was detected in pigpens [4.50 sandflies/(light·night)]. CONCLUSIONS: P. chinensis was predominantly distributed in hilly areas of northern and central-western Henan Province in 2023, and the sandfly density appeared a unimodal distribution. Intensified monitoring of visceral leishmaniasis vectors is recommended.


Subject(s)
Insect Vectors , Leishmaniasis, Visceral , Psychodidae , Seasons , Animals , China , Leishmaniasis, Visceral/transmission , Leishmaniasis, Visceral/epidemiology , Insect Vectors/physiology , Insect Vectors/parasitology , Psychodidae/physiology , Psychodidae/parasitology , Female , Humans , Phlebotomus/physiology , Phlebotomus/parasitology
16.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(4): 334-338, 2024 Jul 29.
Article in Chinese | MEDLINE | ID: mdl-39322291

ABSTRACT

OBJECTIVE: To investigate the spatiotemporal clustering characteristics of the reported incidence of visceral leishmaniasis (VL) in Gansu Province from 1993 to 2023, so as to provide insights into the containment of VL and prevention of VL recurrence. METHODS: County (district)-level epidemical data of VL in Gansu Province from 1993 to 2023 were collected, and the geographical information database of reported VL incidence in Gansu Province was created according to the county-level administrative code and electronic maps in Gansu Province. In addition, the spatial autocorrelation analysis and hot spot analysis of the reported VL incidence were performed in Gansu Province using the software ArcGIS 10.8. RESULTS: A total of 2 597 VL cases were reported in Gansu Province from 1993 to 2023, with an annual average incidence rate of 3.036/105. Spatial autocorrelation analysis showed spatial clustering of the reported VL incidence in Gansu Province (Moran's I = 0.605, Z = 5.240, P < 0.001), appearing high-high clustering features (Getis-Ord G = 0.080, Z = 4.137, P < 0.001), and high-high clustering of the reported incidence of VL was identified in Diebu County, Tanchang County, Zhouqu County and Wenxian County. Hot spot analysis showed hot-spot areas of the reported VL incidence in Tanchang County, Zhouqu County, Wudu District and Wenxian County along the Bailong River basins and cold-spot areas in Qin'an County and Gangu County. CONCLUSIONS: There was spatial clustering and hot spots of the reported VL incidence in Gansu Province from 1993 to 2023. Intensified surveillance and control is required to prevent the spread of VL.


Subject(s)
Leishmaniasis, Visceral , Spatio-Temporal Analysis , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/prevention & control , Leishmaniasis, Visceral/parasitology , Humans , China/epidemiology , Cluster Analysis , Incidence
17.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(4): 403-406, 2024 Jul 31.
Article in Chinese | MEDLINE | ID: mdl-39322302

ABSTRACT

OBJECTIVE: To investigate the distribution and seasonal fluctuations of visceral leishmaniasis vectors sandflies in Lüliang City, Shanxi Province, so as to provide insights into assessment of the visceral leishmaniasis transmission risk and formulation of visceral leishmaniasis control measures. METHODS: A total of 12 natural villages were sampled from Shilou County, Lishi District, Lanxian County, Linxian County and Wenshui County in Lüliang City, Shanxi Province from June to September, 2023, and sandflies were captured using light traps from 7 breeding habitats, including farmers' houses, sheep pens, cattle pens, chicken coops, pig pens, mule and horse pens, and loess-cave dwellings. Following morphological identification of the sandfly species, the distribution of sandflies and the seasonal fluctuations of the sandfly density were analyzed. In addition, the Leishmania was detected in sandflies using a real-time fluorescence quantitative PCR assay. RESULTS: A total of 2 831 sandflies were captured with 156 light traps in Lüliang City from June to September, 2023, including 2 638 female sandflies (93.18%) and 193 male sandflies (6.82%), and the average density was 16.91 sandflies/(light-night). The seasonal fluctuations of the sandfly density all appeared a unimodal distribution in all survey sites, and the sandfly density peaked in July and then declined rapidly. Among all types of breeding habitats, the greatest sandfly density was found in sheep pens [39.04 sandflies/(light-night)]. In addition, 4.08% (2/49) of the sandfly samples were tested positive for Leishmania nucleic acid as revealed by the real-time fluorescence quantitative PCR assay. CONCLUSIONS: Sandflies were widely distributed in Lüliang City, Shanxi Province in 2023, and the peak of the sandfly density was observed in July, which had a visceral leishmaniasis transmission risk. Intensified surveillance of visceral leishmaniasis and sandfly vectors is required and targeted vector control is recommended.


Subject(s)
Insect Vectors , Leishmaniasis, Visceral , Psychodidae , Seasons , Animals , Leishmaniasis, Visceral/transmission , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/parasitology , China , Insect Vectors/physiology , Insect Vectors/parasitology , Psychodidae/physiology , Psychodidae/parasitology , Psychodidae/classification , Female , Male
18.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(4): 393-398, 2024 Jul 30.
Article in Chinese | MEDLINE | ID: mdl-39322300

ABSTRACT

OBJECTIVE: To analyze the characteristics of visceral leishmaniasis cases in Henan Province, so as to provide insights into formulation of the visceral leishmaniasis control srtrategy. METHODS: All epidemiological data of reported visceral leishmaniasis cases in Henan Province from 2021 to 2023 were retrieved from the National Notifiable Disease Report Information Management System of Chinese Center for Disease Control and Prevention, and the epidemiological features and diagnosis of visceral leishmaniasis cases were descriptively analyzed. RESULTS: A total of 93 visceral leishmaniasis cases were reported in Henan Province from 2021 to 2023, with a male to female ratio of 2.58∶1, and including 2 imported cases from other provinces and 91 local cases. The number of visceral leishmaniasis cases peaked during the period between March and May, and between July and October. The reported visceral leishmaniasis cases had ages of 7 months to 74 years, with the largest number of cases found at ages of 0 to 9 years (26 cases, 27.96%), followed by at ages of 60 to 70 years (24 cases, 25.81%). Farmer (47 cases, 50.54%) and diaspora children (19 cases, 20.43%) were predominant occupations, and 91 local visceral leishmaniasis cases were found in 6 cities of Zhengzhou, Luoyang, Anyang, Hebi, Sanmenxia and Xuchang. The median duration from onset of visceral leishmaniasis to diagnosis was 20 days, and there were 25.81% (24/93) cases with 10 days and less duration from onset to diagnosis, 38.71% (36/93) cases receiving diagnosis at 11 to 30 days following onset, and 35.48% (33/93) cases receiving diagnosis for more than 30 days following onset. All cases were predominantly diagnosed in province- (60.00%) and city-level (28.89%) medical institutions. CONCLUSIONS: The number of visceral leishmaniasis is on the rise in Henan Province, with a gradually expanding coverage. Intensified monitoring of visceral leishmaniasis cases, dogs, and vectors, dog management, sandflies control and improved individual protection are recommended to prevent the spread of visceral leishmaniasis.


Subject(s)
Leishmaniasis, Visceral , Leishmaniasis, Visceral/epidemiology , Humans , China/epidemiology , Male , Child, Preschool , Female , Child , Adolescent , Middle Aged , Adult , Infant , Aged , Young Adult , Animals , Dogs , Infant, Newborn
19.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(4): 388-392, 2024 May 22.
Article in Chinese | MEDLINE | ID: mdl-39322299

ABSTRACT

OBJECTIVE: To investigate the epidemiological characteristics of local visceral leishmaniasis in Beijing Municipality from 2021 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy. METHODS: Epidemiological data of visceral leishmaniasis cases reported in Beijing Municipality from 2021 to 2023 were collected from the National Health Informatization Disease Prevention and Control Information System, and the epidemiological characteristics of local visceral leishmaniasis cases were analyzed using a descriptive epidemiological method. In November 2021 and 2023, 50 to 100 permanent residents were voluntarily selected within a 100 meter radius of sites where patients lived or acquired Leishmania infections, and venous blood was sampled for anti-Leishmania antibody testing. Venous blood was sampled from dogs for anti-Leishmania antibody testing in natural villages where patients lived or acquired Leishmania infections, or in districts where Leishmania infected dogs were reported. In addition, sandflies were captured with CO2 mosquito traps and fine mesh nets in natural villages where patients lived or acquired Leishmania infections from May to September, 2021 and 2023, for sandfly species identification. RESULTS: A total of 4 local visceral leishmaniasis cases were reported in Beijing Municipality from 2021 to 2023, with ages of 2 to 77 years, and acquiring Leishmania infections in Mentougou District (2 cases), Changping District (1 case), and Yanqing District (1 case). The anti-Leishmania antibody testing was all negative in 73 human blood samples and the sero-prevalence of anti-Leishmania antibody was 25.00% in 36 venous blood samples from domestic dogs in 2021, with a total of 4 520 Phlebotomus chinensis captured. The sero-prevalence of anti-Leishmania antibody was 0.51% in 198 human blood samples and 13.58% in 243 venous blood samples from domestic dogs in 2023, with 16.10%, 25.00%, 17.78% and 3.13% sero-prevalence in dogs sampled from Mentougou District, Changping District, Yanqing District and Haidian District, respectively (P = 0.011), while a total of 1 712 Ph. chinensis were captured, including 1 421 female sandflies (86.54%). CONCLUSIONS: The prevalence of local visceral leishmaniasis was low in Beijing Municipality from 2021 to 2023; however, there is a risk of further spread in the epidemic foci. Intensified visceral leishmaniasis surveillance and control is recommended.


Subject(s)
Leishmaniasis, Visceral , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/veterinary , Humans , Animals , Dogs , Male , Female , Middle Aged , Adult , Aged , Child , Young Adult , Child, Preschool , Adolescent , Beijing/epidemiology , Dog Diseases/epidemiology , Dog Diseases/parasitology , Psychodidae/parasitology , Psychodidae/physiology , China/epidemiology
20.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(4): 399-402, 2024 Aug 05.
Article in Chinese | MEDLINE | ID: mdl-39322301

ABSTRACT

OBJECTIVE: To investigate the prevalence of canine Leishmania infections in villages endemic for visceral leishmaniasis in Xin'an County, Luoyang City, so as to provide insights into visceral leishmaniasis prevention and control. METHODS: All dogs were captured from Huzhanggou Village, Xin'an County, Luoyang City in August 2020, where local cases with visceral leishmaniasis lived. The basic characteristics of dogs were collected, and venous blood was collected via the ear or neck veins of dogs. The serum anti-Leishmania antibody was detected using the rk39 immunochromatographic test and Leishmania nucleic acid was detected using PCR assay, and the prevalence of Leishmania infection was estimated in dogs. RESULTS: A total of 133 domestic dogs were captured from Huzhanggou Village, with a median age of 18.0 (28.5) months. The sero-prevalence of anti-Leishmania antibody was 24.81% (33/133) and the prevalence of a positive PCR assay was 14.29% (19/133) in dogs. The median ages of Leishmania-infected and uninfected dogs were 24.0 (36.0) months and 12.0 (18.0) months, respectively (U = 872.000, P = 0.000), and the prevalence of Leishmania infection was 55.56% (5/9) in "mangy dogs" and 24.19% (30/124) in asymptomatic dogs (χ2 = 2.793, P = 0.095). CONCLUSIONS: There are a large number of asymptomatic dogs with Leishmania infections in Xin'an County, Luoyang City, with a high transmission risk of visceral leishmaniasis. Timely prevention and control measures are required to control the spread of visceral leishmaniasis.


Subject(s)
Dog Diseases , Animals , Dogs , Dog Diseases/epidemiology , Dog Diseases/parasitology , Prevalence , China/epidemiology , Male , Female , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/veterinary , Leishmaniasis, Visceral/parasitology , Leishmaniasis/epidemiology , Leishmaniasis/veterinary , Leishmania/isolation & purification , Leishmania/immunology , Antibodies, Protozoan/blood , Cities/epidemiology
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