Visceral Leishmaniasis Research Articles

Prevalence of anti-Trypanosoma cruzi and anti-Leishmania infantum antibodies in domestic dogs from Tremedal, Bahia: insights from the Oxente Chagas Bahia Project

BackgroundChagas disease (CD) and visceral leishmaniasis (VL) are two important zoonotic diseases that present significant public health challenges in Latin America. Domestic dogs, due to their close contact with humans, serve as key reservoirs for both Trypanosoma cruzi (the causative agent of CD) and Leishmania infantum (the causative agent of VL), making them important sentinels in disease surveillance. This study, conducted as part of the Oxente Chagas Bahia Project, aimed to assess the seroprevalence of anti-T. cruzi and anti-L. infantum antibodies in domestic dogs from Tremedal, Bahia, Brazil.MethodsSerum samples from 17 dogs were analyzed using indirect enzyme-linked immunosorbent assay (ELISA) (using recombinant antigens (IBMP-8.1, IBMP-8.2, IBMP-8.3, IBMP-8.4) for T. cruzi and the TR DPP® rapid test and ELISA for L. infantum.ResultsThe results showed that 5.9% (1/17) of the dogs tested were seropositive for T. cruzi, indicating the presence of the parasite in the region. Similarly, 5.9% (1/17) of the dogs were confirmed to be positive for L. infantum by ELISA, although the results of the TR DPP® test initially suggested a higher prevalence (41.2%), highlighting the risk of false-positive results.ConclusionsThese findings underscore the critical role of dogs in CD and VL surveillance, given their involvement in both domestic and peridomestic transmission cycles. The study also emphasizes the need for confirmatory testing to ensure diagnostic accuracy, which will contribute to more effective disease control strategies in endemic areas. This work highlights the importance of a One Health approach in which human and animal health are closely monitored to mitigate the transmission of zoonotic diseases.Graphical

Gene deletion as a possible strategy adopted by New World Leishmania infantum to maximize geographic dispersion.

The present study investigates implications of a sub-chromosomal deletion in Leishmania infantum strains, the causative agent of American Visceral Leishmaniasis (AVL). Primarily found in New World strains, the deletion leads to the absence of the ecto-3'-nucleotidase/nuclease enzyme, impacting parasite virulence, pathogenicity, and drug susceptibility. The factors favoring prevalence and the widespread geographic distribution of these deleted mutant parasites (DEL) in the NW (NW) are discussed under the generated data. We conducted phenotypic assessments of the sub-chromosomal deletion through in vitro assays with axenic parasites and experimental infections in both in vitro and in vivo models of vertebrate and invertebrate hosts using geographically diverse mutant field isolates. Despite reduced pathogenicity, the DEL strains efficiently infect vertebrate hosts and exhibit relevant differences, including enhanced metacyclogenesis and colonization rates in sand flies, potentially facilitating transmission. This combination may represent a more effective way to maintain and disperse the transmission cycle of DEL strains. Phenotypic assessments reveal altered parasite fitness, with potential enhanced transmissibility at the population level. Reduced susceptibility of DEL strains to miltefosine, a key drug in VL treatment, further complicates control efforts. The study underscores the importance of typing parasite genomes for surveillance and control, advocating for the sub-chromosomal deletion as a molecular marker in AVL management.

Trends in Post-Kala-Azar Dermal Leishmaniasis in Sudan: Cases, Ethnic Distribution, and Recovery.

Post-kala-azar dermal leishmaniasis (PKDL) is a neglected tropical disease that can develop after treatment of leishmaniasis. It causes significant health risks and serves as a reservoir, perpetuating transmission. Current information on PKDL characteristics is crucial for effective disease management and control. This study aimed to describe clinical and epidemiological characteristics of PKDL patients in eastern Sudan. A retrospective cross-sectional study was conducted on suspected PKDL patients (N = 37) at a tertiary hospital in eastern Sudan. Blood samples were tested for anti-rK39 antibodies to confirm the diagnosis of the disease. Demographic, clinical, and epidemiological data of the PKDL patients were gathered and analyzed. Most PKDL cases (69.4%) came from specific locations involving one ethnic group (94.6%), mainly affecting young males (54.1%). A family history of PKDL was noted in only 27.0% of cases; 51.4% developed PKDL within 1 month after visceral leishmaniasis (VL) treatment. Most cases (56.8%) were grade 1 (a low level of parasitic load), predominantly featuring macular (51.4%), papular (18.9%), and nodular (13.5%) lesions. All patients had skin rashes; 91.9% exhibited no fever, and 29.7% reported itching. Lesions appeared within a month after VL treatment, with most patients recovering spontaneously within 3-18 months. PKDL was particularly prevalent in specific regions and ethnic groups, namely the Masaleet and Dago tribes. These findings can enhance PKDL understanding and management in the region.

T-cell activation and senescence in asymptomatic HIV/Leishmania infantum co-infection.

Leishmania infantum can be an opportunistic pathogen, with an immunocompromised status increasing the risk of converting asymptomatic infection to symptomatic visceral leishmaniasis (VL). VL has approximately 5% fatality rate; and HIV coinfection (AIDS/VL) increases this risk. We hypothesized that, relative to those with HIV alone, people with co-infection would have altered T cell activation which could impact on the risk of VL. A cross-sectional study was performed between 2014 and 2016 to determine the prevalence of L. infantum infection in people living with HIV (PLHIV) residing in Brazil (n = 1,372). Subsequent incident cases of VL were ascertained from a public health database through 2018 and from a cohort of families with VL. Immune status of 69 participants was evaluated and comparisons made between those with and without HIV, with latent or with active Leishmania infection and those without HIV but with active or resolved Leishmania or T cell hypersensitivity to Leishmania antigen and healthy control subjects. A total of 24.2% of PLHIV had positive anti-IgG L. infantum antibodies. The relative risk of developing AIDS/VL was 2.27 (95% CI: 0.920 to 5.59; p = 0.07) to HIV/Leish coinfected subjects with positive leishmania serology compared to HIV subjects without leishmania serology. Poor adherence to antiretroviral therapy (p = 0.0008) or prior opportunistic infections (p = 0.0007) was associated with development of AIDS/VL in asymptomatic HIV/Leish. CD4+ and CD8+ T cells counts or viral load were similar between asymptomatic HIV/Leish and HIV subjects. However, activated CD8+CD38+HLA-DR+ T cells were higher in asymptomatic HIV/Leish than HIV. Likewise, senescent (CD57+) and PD1+ CD8+ T cells were higher in asymptomatic HIV/Leish than in AIDS/VL or HIV groups. Although asymptomatic HIV/Leish subjects had CD4+ and CD8+ T cells similar to HIV alone, their CD8+T cells had increased activation and senescence which could contribute to risk of developing VL.

Unsupervised machine learning identifies biomarkers of disease progression in post-kala-azar dermal leishmaniasis in Sudan.

Post-kala-azar dermal leishmaniasis (PKDL) appears as a rash in some individuals who have recovered from visceral leishmaniasis caused by Leishmania donovani. Today, basic knowledge of this neglected disease and how to predict its progression remain largely unknown. This study addresses the use of several biochemical, haematological and immunological variables, independently or through unsupervised machine learning (ML), to predict PKDL progression risk. In 110 patients from Sudan, 31 such factors were assessed in relation to PKDL disease state at the time of diagnosis: progressive (worsening) versus stable. To identify key factors associated with PKDL worsening, we used both a conventional statistical approach and multivariate analysis through unsupervised ML. The independent use of these variables had limited power to predict skin lesion severity in a baseline examination. In contrast, the unsupervised ML approach identified a set of 10 non-redundant variables that was linked to a 3.1 times higher risk of developing progressive PKDL. Three of these clustering factors (low albumin level, low haematocrit and low IFN-γ production in PBMCs after Leishmania antigen stimulation) were remarkable in patients with progressive disease. Dimensionality re-establishment identified 11 further significantly modified factors that are also important to understand the worsening phenotype. Our results indicate that the combination of anaemia and a weak Th1 immunological response is likely the main physiological mechanism that leads to progressive PKDL. A combination of 14 biochemical variables identified by unsupervised ML was able to detect a worsening PKDL state in Sudanese patients. This approach could prove instrumental to train future supervised algorithms based on larger patient cohorts both for a more precise diagnosis and to gain insight into fundamental aspects of this complication of visceral leishmaniasis.

Visceral leishmaniasis and lymphoma: a rare and dangerous couple

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The vectors are hematophagous (blood-feeding) dipterans of various genera, with humans serving as accidental definitive hosts and, in some cases, as reservoirs. Visceral leishmaniasis more often affects immunocompromised individuals, in whom the protozoan invades and replicates within the host’s macrophages, evading innate and cell-mediated immune responses. We describe the case of a 54-year-old male patient who had not traveled to endemic areas. He presented with progressive asthenia associated with persistent fever, which had been treated at home with nonsteroidal anti-inflammatory drugs and oral betamethasone. During hospitalization, he developed cytopenia and hepatosplenomegaly. Bone marrow biopsy revealed the presence of Leishmania and intravascular large B-cell lymphoma. When faced with cases of fever of unknown origin, clinicians should also investigate opportunistic infections. An underlying condition causing immunosuppression may not be clear, and corticosteroids often alter hematological values, thus masking a hematological disease.

Leishmaniasis in deployed military populations: A systematic review and meta-analysis.

Leishmaniasis affects military personnel deployed to endemic areas following exposure to sand flies infected with the protozoa Leishmania. This systematic review and meta-analysis of data specific to military populations aims to identify knowledge gaps to mitigate sand fly exposure and Leishmania transmission during deployments. The review was registered on PROSPERO (CRD42023463687). Random-effects meta-analyses and narrative synthesis were performed. Thirty-six studies were included, most of which reported on cutaneous leishmaniasis (CL), showing a mean cumulative incidence of 10% (95% CI: 5-16), suggesting higher rates in the Eastern Mediterranean region (14% [95% CI: 12-16]) compared to the African region (8%) and American region (9%). Asymptomatic Leishmania infection had a cumulative incidence of 11% (95% CI: 6-17), with higher rates in Eastern Mediterranean countries (20% [95% CI: 14-25]). Diagnosis involved parasitological, serological, and molecular methods, with L. (L) mexicana and L. (V.) braziliensis identified as the predominant CL pathogens in deployed troops in the Americas. Visceral leishmaniasis cases were less frequent, all reported from the Eastern Mediterranean and associated with the Leishmania donovani/infantum complex; whereas CL cases in the Old World were due predominantly to L. major and L. tropica. Regular use of long-lasting insecticidal nets to mitigate sand fly exposure demonstrated high potential effectiveness than other reported personal protective measures (PPMs) which yielded mixed or inconclusive results. In summary, the systematic review revealed the substantial variability between study designs and statistical integrity. There is need for more consistent and robustly designed studies including well-define controls and replication. Future studies would be advised to explore the long-term effectiveness and practicality of PPMs, both individually and in combination, across diverse deployment settings.

Infantile visceral leishmaniasis disguised as Kawasaki disease.

Infantile visceral leishmaniasis disguised as Kawasaki disease.

Kala-azar elimination in India: reflections on success and sustainability.

The incidence and mortality of kala-azar (KA, visceral leishmaniasis) in India have fallen drastically in the past few years, and in 2023 the reported KA incidence reached the threshold for elimination as a public health problem (<1 case/10 000 of population at subdistrict level). One of the strategies adopted by India's kala-azar elimination program (KAEP) was the regular independent assessment of the program implementation by teams of experts. We present the findings of assessments undertaken in 2019, 2021 and 2023, when the KAEP was in the last mile of elimination. Factors that contributed to its success were political commitment, intensified implementation, a strong network of KA partners and committed donors. Bottlenecks were observed in disease surveillance, data utilization, vector-control operations and program management at implementation. To sustain the gains and achieve validation of elimination, the KAEP should continue the following minimal essential services: optimized active and passive case detection and management of KA, post-KA dermal leishmaniasis, KA-HIV coinfection and relapse supported by vector-control interventions. Long-term measures that will sustain elimination are overall socioeconomic development, including improved living conditions, parallel with efficient surveillance and operational research that is aligned with the changing epidemiology of the disease.

Unraveling the Role of Proteinopathies in Parasitic Infections

Proteinopathies, characterized by the misfolding, aggregation, and deposition of proteins, are hallmarks of various neurodegenerative and systemic diseases. Increasingly, research has highlighted the role of protein misfolding in parasitic infections, unveiling intricate interactions between host and parasite that exacerbate disease pathology and contribute to chronic outcomes. The life cycles of parasitic protozoa, including Plasmodium, Toxoplasmosis, and Leishmania species, are complicated and involve frequent changes between host and vector environments. Their proteomes are severely stressed during these transitions, which calls for highly specialized protein quality control systems. In order to survive harsh intracellular conditions during infection, these parasites have been demonstrated to display unique adaptations in the unfolded protein response, a crucial pathway controlling endoplasmic reticulum stress. In addition to improving parasite survival, these adaptations affect host cell signaling and metabolism, which may jeopardize cellular homeostasis. By causing oxidative stress, persistent inflammation, and disturbance of cellular proteostasis, host–parasite interactions also contribute to proteinopathy. For instance, Plasmodium falciparum disrupts normal protein homeostasis and encourages the accumulation of misfolded proteins by influencing host redox systems involved in protein folding. In addition to interfering with host chaperone systems, the parasitic secretion of effector proteins exacerbates protein misfolding and aggregate formation. Autophagy, apoptosis regulation, organelle integrity, and other vital cellular processes are all disrupted by these pathological protein aggregates. Long-term misfolding and aggregation can cause irreversible tissue damage, which can worsen the clinical course of illnesses like visceral leishmaniasis, cerebral malaria, and toxoplasmosis. Treating parasite-induced proteinopathies is a potentially fruitful area of therapy. According to recent research, autophagy modulators, proteasome enhancers, and small-molecule chaperones may be repurposed to lessen these effects. Pharmacological agents that target the UPR, for example, have demonstrated the ability to decrease parasite survival while also reestablishing host protein homeostasis. Targeting the proteins secreted by parasites that disrupt host proteostasis may also offer a novel way to stop tissue damage caused by proteinopathies. In conclusion, the intersection of protein misfolding and parasitic infections represents a rapidly advancing field of research. Dissecting the molecular pathways underpinning these processes offers unprecedented opportunities for developing innovative therapies. These insights could not only transform the management of parasitic diseases but also contribute to a broader understanding of proteinopathies in infectious and non-infectious diseases alike.

Seroprevalence of Toscana virus in blood donors in mainland Portugal

BackgroundToscana virus (TOSV; Phlebovirus toscanaense), a phlebovirus transmitted by sand flies, is a growing public health concern in the Mediterranean region, with infections often being asymptomatic but potentially leading to neuroinvasive disease. Despite its presence in neighboring countries, data on TOSV seroprevalence in Portugal are limited. This study aimed to estimate the national seroprevalence of TOSV among blood donors in mainland Portugal and explore associations with sociodemographic factors and Leishmania infection.MethodsA cross-sectional study was conducted using serum samples from 3593 blood donors across mainland Portugal, collected between February and June 2022. Anti-TOSV antibodies were detected via microneutralization assay, and anti-Leishmania antibodies had previously been tested using ELISA. Sociodemographic data were obtained from self-administered questionnaires. Seroprevalence was estimated by region, and multivariate logistic regression was used to identify factors associated with TOSV infection.ResultsOverall, the estimated national true seroprevalence of TOSV was 2.6% (95% CI 2.1–3.1%). Regional seroprevalence varied significantly, with the highest values (up to 14.8%) in Alto Alentejo, Baixo Alentejo, Douro, Alto Tâmega e Barroso and Oeste regions. Multivariate analysis showed that age ≥ 50 years (aOR 1.70, 95% CI 1.04–2.77), residing in the Alentejo region (aOR 3.05, 95% CI 1.85–5.02) and positive/borderline Leishmania serology (aOR 2.31, 95% CI 1.29–4.15) were significantly associated with TOSV infection.ConclusionsThis study highlights new areas of TOSV circulation in Portugal, particularly in regions with higher Leishmania seroprevalence and visceral leishmaniasis incidence, suggesting co-circulation of these pathogens. Although a lower seroprevalence was obtained compared to neighboring countries, TOSV should still be considered in the differential diagnosis of viral meningitis and encephalitis in Portugal, especially in potentially high-risk regions. Further research is needed to better understand the ecological drivers of TOSV distribution in Portugal.Graphical

TGF-beta plays dual roles in immunity and pathogenesis in leishmaniasis.

TGF-beta plays dual roles in immunity and pathogenesis in leishmaniasis.

Urine-based ELISA using a recombinant chimeric protein for the diagnosis of paucibacillary and multibacillary leprosy.

Urine-based ELISA using a recombinant chimeric protein for the diagnosis of paucibacillary and multibacillary leprosy.

Diagnostic techniques for visceral leishmaniasis: An overview of methods used in East Africa.

Diagnostic techniques for visceral leishmaniasis: An overview of methods used in East Africa.

Impact of Marasmic Malnutrition on Visceral Leishmaniasis: Progression and Treatment Efficacy in a Murine Model.

Malnutrition and visceral leishmaniasis are major public health problems that are responsible for millions of deaths across many countries. Leishmaniasis development and progression are associated with the host immune status. In this context, malnutrition can directly affect the course of leishmaniasis, impairing several components of the immune system. Moreover, malnutrition directly interferes with the tropism of Leishmania in organs, affecting host susceptibility. Therefore, this work aimed to evaluate the influence of nutritional status on the establishment, progression, and treatment of Leishmania infantum infection in malnourished and refed mice. BALB/c mice were fed either a control or restricted diet, infected with L. infantum promastigotes, and treated with meglumine antimoniate, the standard drug for treating visceral leishmaniasis. The effects of infection were evaluated through limiting dilution analysis (LDA). Compared with control mice, malnourished and refed mice presented a lower parasitic load in the spleen, which correlated with spleen atrophy, and the refeeding process partially reversed but did not fully rescue the infection status. Both groups presented a high parasitic load in the liver. Marasmic malnutrition appeared to impair the efficacy of leishmaniasis treatment; however, the refed groups exhibited a robust decrease in the parasite load, which was comparable to that in the control group subjected to treatment. Our data suggested that marasmic malnutrition affects the establishment and progression of Leishmania infection, in addition to reducing the efficacy of standard treatment. Furthermore, the refeeding intervention used did not fully reverse the observed effects. These findings highlight the potential importance of nutritional interventions in the clinical management of visceral leishmaniasis in malnourished populations.

Whole-exome sequencing identifies EP300 variants associated with visceral leishmaniasis relapse.

Whole-exome sequencing identifies EP300 variants associated with visceral leishmaniasis relapse.

Patient insights research exploring disease awareness, patient life experience, and current management of visceral leishmaniasis in Bihar, India.

Visceral leishmaniasis (VL) is a vector-borne disease caused by Leishmania parasites and transmitted by sand fly bites, targeted for elimination in India. VL primarily affects rural, low-income populations with limited health care access. In South Asia, few studies have explored patients' perspectives, diagnoses, and treatment experiences; particularly lacking an understanding about the patients' life experiences outside of clinical research settings. A qualitative study was conducted in Bihar, India, using moderator-facilitated, protocol-defined discussion. Eighteen adult patients and 12 caregivers of children diagnosed with and treated for VL within the last 12 months were identified by self-report. Mean time from symptom onset to diagnosis was 13.8 days. Challenges of the early patient life experience included lack of urgency by health care professionals, delayed diagnosis, and no guarantee of treatment at the location of their VL diagnosis (63% had to switch to a different center for treatment, at times delaying treatment). Key barriers identified in previous studies that were re-confirmed in this study include out-of-pocket financial burden, absence from work/home duties, and long-distance travel to hospitals. Patients and caregivers (n = 29/30) expressed a preference for a potential oral treatment that could be taken close to home. This study reveals new insights about the patient life experience and reconfirms previous research indicating that access to care for patients with VL in the Bihar area remains a challenge. Although most patients with VL seek care early, diagnosis often requires multiple visits to a health care facility. Despite access to therapy in public hospitals, some patients reported a preference for private care. Even if diagnosis takes place in a government-funded public setting, some patients reported needing to move from the location of diagnosis to another center to receive therapy, creating an additional burden for patients. As a potential alternative to current parenteral treatment, adult patients and caregivers of pediatric patients expressed interest in a potential oral therapy because it may reduce barriers to access care.

Some zoonotic infectious diseases are prevalent among children under 15 years of age in Ardabil Province, northern Iran

BackgroundThis study sought to investigate the seroprevalence of visceral leishmaniasis (VL), toxocariasis, brucellosis, and salmonellosis, as well as their co-infection and potential cross-reaction, in children under 15 years referred to health centers in Ardabil province, Iran, from 2019 to 2021.MethodsThe current study examined 1,550 serum samples using direct agglutination test (DAT), Toxocara canis ELISA, Wright, and Widal tests to detect antibodies against Leishmania, Toxocara, Brucella, and Salmonella, respectively. We also compared the test results to determine the possibility of cross-reactivity or simultaneous seropositivity in the tested samples.ResultsIn general, anti-Leishmania antibodies were positive in 78 samples (5%) at titers of ≥ 1:800, while only 8 cases had titers of ≥ 1:3200, which was considered as positive result. Therefore, the seroprevalence of VL was estimated to be at 5.16 per 1,000 at-risk populations. Meshkin-Shahr city had the highest seroprevalence (7 cases, 87.5%), followed by Ardabil (1 case, 12.5%) (p = 0.03). The highest and lowest seropositivity rates were observed in children aged 1–5 (6 samples, 75%) and 5–15 (2 samples, 25%) years old, respectively (p = 0.02). Anti-Toxocara antibodies were positive in 249 samples, (16.1%, 95% CI: 13.2–18.8), which were primarily males. There was a significant difference in seropositivity to Toxocara infection by city (p = 0.04), and age (p = 0.00). The results of Wright test showed seropositivity of 7.5% (117 samples) with the highest rate in individuals aged ≥ 10 years, males, and urban areas. No significant differences existed between the seropositivity rate and age, sex, residency, or symptoms (p > 0.05). Widal test was positive in 6% (94 samples) of children, with most cases being females (p < 0.05), particularly in those aged ≥ 10 years. Of the 78 DAT-positive sera, only 2 samples with a low titer (1:800) tested positive for anti-Toxocara antibodies, while none of the high titer samples were positive. In addition, samples with a DAT titer of 1:800 were positive for anti-Brucella (1:40: 10.2%, 1:80: 2.5%) and Salmonella (1:40: 3.8%) antibodies. The titers were (1:40: 5.1%, 1:80: 1.3%) for Brucella and (1:40: 2.5%) for Salmonella at a 1:1600 DAT titer. Wright's test on Toxocara-positive sera showed that 1.2% and 0.4% of samples had titers of 1:40 and 1:80, respectively. Furthermore, 2%, 2.8%, and 0.8% of Toxocara-positive samples exhibited anti-Salmonella antibodies at titers of 1:40, 1:40, and 1:80 corresponding to OA and OD antigens, respectively. The Wright (OR:1.099; 95% CI:1.080–1.118) and Widal (OR: 1.078; 95% CI: 1.062–1.094) tests showed cross-reactivity at low titers and minimal co-infection at high titers. Of Widal-positive sera, 11.4% with a titer of 1:40, and 2.7% with a titer of 1:80 were positive for anti-Brucella antibodies (OR:1.078; 95% CI:1.056–1.085).ConclusionGiven the prevalence of bacterial and parasitic febrile infections among children in the region, and their symptomatic similarity to VL, it is crucial to recognize clinical manifestations, accurately diagnose co-infections, and account for cross-reactivity in serological tests.

Evaluation of Immunopharmacological efficacy of live Leishmania donovani overexpressing Ld_ζ1domain for protection against experimental human visceral Leishmaniasis.

Evaluation of Immunopharmacological efficacy of live Leishmania donovani overexpressing Ld_ζ1domain for protection against experimental human visceral Leishmaniasis.

Discrepancies in neglected tropical diseases burden estimates in China: comparative study of real-world data and Global Burden of Disease 2021 data (2004-2020)

ObjectivesTo assess the discrepancies between real-world data and the Global Burden of Disease (GBD) 2021 estimates for six neglected tropical diseases in China. Additionally, to evaluate the applicability of the...