Humans seropositive for Trypanosoma cruzi co-infected with intestinal helminths have higher infectiousness, parasitaemia and Th2-type response in the Argentine Chaco.

BACKGROUND: The Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco. METHODS: We conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry. RESULTS: The seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients. CONCLUSIONS: Our results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients.

In Vitro and In Silico Evaluation of the Leishmanicidal and Trypanocidal Activities of Lignan Methylpiperitol Isolated from Persea Fulva.

Neglected Tropical Diseases are a significant concern as they encompass various infections caused by pathogens prevalent in tropical regions. The limited and often highly toxic treatment options for these diseases necessitate the exploration of new therapeutic candidates. In the present study, the lignan methylpiperitol was isolated after several chromatographic steps from Persea fulva L. E. Koop (Lauraceae) and its leishmanicidal and trypanocidal activities were evaluated using in vitro and in silico approaches. The chemical structure of methylpiperitol was defined by NMR and MS spectral data analysis. The antiprotozoal activity of methylpiperitol was determined in vitro and indicated potency against trypomastigote forms of Trypanosoma cruzi (EC50 of 4.5±1.1 mM) and amastigote forms of Leishmania infantum (EC50 of 4.1±0.5 mM), with no mammalian cytotoxicity against NCTC cells (CC50>200 mM). Molecular docking studies were conducted using six T. cruzi and four Leishmania. The results indicate that for the molecular target hypoxanthine phosphoribosyl transferase in T. cruzi and piteridine reductase 1 of L. infatum, the methylpiperitol obtained better results than the crystallographic ligand. Therefore, the lignan methylpiperitol, isolated from P. fulva holds potential for the development of new prototypes for the treatment of Neglected Tropical Diseases, especially leishmaniasis.

Innovating Leishmaniasis Treatment: A Critical Chemist's Review of Inorganic Nanomaterials.

Leishmaniasis, a critical Neglected Tropical Disease caused by Leishmania protozoa, represents a significant global health risk, particularly in resource-limited regions. Conventional treatments are effective but suffer from serious limitations, such as toxicity, prolonged treatment courses, and rising drug resistance. Herein, we highlight the potential of inorganic nanomaterials as an innovative approach to enhance Leishmaniasis therapy, aligning with the One Health concept by considering these treatments' environmental, veterinary, and public health impacts. By leveraging the adjustable properties of these nanomaterials─including size, shape, and surface charge, tailored treatments for various diseases can be developed that are less harmful to the environment and nontarget species. We review recent advances in metal-, oxide-, and carbon-based nanomaterials for combating Leishmaniasis, examining their mechanisms of action and their dual use as standalone treatments or drug delivery systems. Our analysis highlights a promising yet underexplored frontier in employing these materials for more holistic and effective disease management.

Leprosy knowledge among primary care physicians in Southern Brazil: are we underdiagnosing?

BACKGROUND: Leprosy is a chronic infection with high morbidity in Brazil. Primary care physicians' lack of knowledge about the disease may play a significant role in underdiagnosis. This study aimed to assess primary care physicians' ability to identify typical leprosy skin lesions and their knowledge of the subject. METHODS: This cross-sectional study relied on a questionnaire in which participating doctors chose one main diagnostic hypothesis and two differential diagnoses for each skin lesion presented. Five leprosy lesions were included. Questions regarding management, follow-up, and diagnostic workup for the disease were also included. The questionnaire was sent to primary care physicians working in Curitiba, in the Southern Brazilian state of Paraná, and dermatologists, who constituted the control group. RESULTS: Thirty-two primary care physicians and 26 dermatologists agreed to participate in the study. Primary care physicians accurately identified a mean of 1.8 ± 1.2 of the five leprosy skin lesions, while dermatologists accurately identified 2.5 ± 0.9 (P = 0.009). The main misdiagnosed leprosy forms were the lepromatous and histoid variants. Among primary care physicians, 56.2% claimed to have little knowledge of the subject and a large share of participants was unaware of recent updates in treating paucibacillary forms, even within the dermatologist subgroup. CONCLUSIONS: Primary care physicians in Curitiba have little information regarding the diagnosis, treatment, and follow-up of leprosy. Even dermatologists had difficulties with treatment and patient management, emphasizing the constant need for education on this subject.

First detection of feline sporotrichosis (Sporothrix brasiliensis) at the zoonoses control service in Campo Grande, Mato Grosso do sul, Brazil.

Sporotrichosis is a traumatic mycosis affecting the skin or subcutaneous tissues caused by Sporothrix dimorphic fungus. The fungal complex includes several pathogenic species, out of which S. brasiliensis and S. schenckii are predominant in Brazil. In Mato Grosso do Sul (MS) state, the first human and animal cases were reported in 2016 in Corumbá and Ladário cities. Accordingly, we present the first occurrences of feline sporotrichosis detected in the state capital Campo Grande, MS, by the Zoonoses Control Service (ZCS) of the Municipal Public Health Department. The study included four allochthonous cases of feline sporotrichosis originating from Corumbá, MS, attended by the ZCS. All four cats presented classical clinical signs of sporotrichosis, as ulcerative nodular cutaneous lesions. Three slides tested positive by direct microscopy and PCR, followed by Sanger sequencing confirmed Sporothrix brasiliensis in two samples. The initial suspicion and diagnosis of feline sporotrichosis at the ZCS highlights the importance of accurate surveillance of sporotrichosis in non-endemic areas to enhance the capacity to prevent, detect and respond to emerging diseases in Campo Grande.

Multi-target Compounds against Trypanosomatid Parasites and Mycobacterium tuberculosis.

Multi-target drug treatment has become popular as a substitute for traditional monotherapy. Monotherapy can lead to resistance and side effects. Multi-target drug discovery is gaining importance as data on bioactivity becomes more abundant. The design of multi-target drugs is expected to be an important development in the pharmaceutical industry in the near future. This review presents multi-target compounds against trypanosomatid parasites (Trypanosoma cruzi, T. brucei, and Leishmania sp.) and tuberculosis (Mycobacterium tuberculosis), which mainly affect populations in socioeconomically unfavorable conditions. The article analyzes the studies, including their chemical structures, viral strains, and molecular docking studies, when available. The objective of this review is to establish a foundation for designing new multi-target inhibitors for these diseases.

Leishmaniinae: Evolutionary inferences based on protein expression profiles (PhyloQuant) congruent with phylogenetic relationships among Leishmania, Endotrypanum, Porcisia, Zelonia, Crithidia, and Leptomonas.

Evolutionary relationships among parasites of the subfamily Leishmaniinae, which comprises pathogen agents of leishmaniasis, were inferred based on differential protein expression profiles from mass spectrometry-based quantitative data using the PhyloQuant method. Evolutionary distances following identification and quantification of protein and peptide abundances using Proteome Discoverer and MaxQuant software were estimated for 11 species from six Leishmaniinae genera. Results clustered all dixenous species of the genus Leishmania, subgenera L. (Leishmania), L. (Viannia), and L. (Mundinia), sister to the dixenous species of genera Endotrypanum and Porcisia. Placed basal to the assemblage formed by all these parasites were the species of genera Zelonia, Crithidia, and Leptomonas, so far described as monoxenous of insects although eventually reported from humans. Inferences based on protein expression profiles were congruent with currently established phylogeny using DNA sequences. Our results reinforce PhyloQuant as a valuable approach to infer evolutionary relationships within Leishmaniinae, which is comprised of very tightly related trypanosomatids that are just beginning to be phylogenetically unraveled. In addition to evolutionary history, mapping of species-specific protein expression is paramount to understand differences in infection processes, tissue tropisms, potential to jump from insects to vertebrates including humans, and targets for species-specific diagnostic and drug development.

Advancing arbovirus diagnosis in Brazil: strengthening diagnostic strategies and public health data collection.

BACKGROUND: The last five decades have seen a surge in viral outbreaks, particularly in tropical and subtropical regions like Brazil, where endemic arboviruses such as Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) pose significant threats. However, current diagnostic strategies exhibit limitations, leading to gaps in infection screening, arbovirus differential diagnoses, DENV serotyping, and life-long infection tracking. This deficiency impedes critical information availability regarding an individual's current infection and past infection history, disease risk assessment, vaccination needs, and policy formulation. Additionally, the availability of point-of-care diagnostics and knowledge regarding immune profiles at the time of infection are crucial considerations. OBJECTIVES: This review underscores the urgent need to strengthen diagnostic methods for arboviruses in Brazil and emphasizes the importance of data collection to inform public health policies for improved diagnostics, surveillance, and policy formulation. METHODS: We evaluated the diagnostic landscape for arboviral infections in Brazil, focusing on tailored, validated methods. We assessed diagnostic methods available for sensitivity and specificity metrics in the context of Brazil. RESULTS: Our review identifies high-sensitivity, high-specificity diagnostic methods for arboviruses and co-infections. Grifols transcription-mediated amplification assays are recommended for DENV, CHIKV, and ZIKV screening, while IgG/IgM ELISA assays outperform Rapid Diagnostic Tests (RDTs). The Triplex real-time RT-PCR assay is recommended for molecular screening due to its sensitivity and specificity. CONCLUSION: Enhanced diagnostic methods, on-going screening, and tracking are urgently needed in Brazil to capture the complex landscape of arboviral infections in the country. Recommendations include nationwide arbovirus differential diagnosis for DENV, ZIKV, and CHIKV, along with increased DENV serotyping, and lifelong infection tracking to combat enduring viral threats and reduce severe presentations.

Optimization of benzenesulfonyl derivatives as anti-Trypanosomatidae agents: Structural design, synthesis, and pharmacological assessment against Trypanosoma cruzi and Leishmania infantum.

Leishmaniasis and Chagas disease are neglected tropical diseases caused by Trypanosomatidae parasites. Given the numerous limitations associated with current treatments, such as extended treatment duration, variable efficacy, and severe side effects, there is an urgent imperative to explore novel therapeutic options. This study details the early stages of hit-to-lead optimization for a benzenesulfonyl derivative, denoted as initial hit, against Trypanossoma cruzi (T. cruzi), Leishmania infantum (L. infantum) and Leishmania braziliensis (L. braziliensis). We investigated structure - activity relationships using a series of 26 newly designed derivatives, ultimately yielding potential lead candidates with potent low-micromolar and sub-micromolar activities against T. cruzi and Leishmania spp, respectively, and low in vitro cytotoxicity against mammalian cells. These discoveries emphasize the significant promise of this chemical class in the fight against Chagas disease and leishmaniasis.

A pilot study to address the mental health of persons living with lymphatic filariasis in Léogâne, Haiti: Implementing a chronic disease self-management program using a stepped-wedge cluster design.

BACKGROUND: Neglected tropical diseases (NTDs) inflict significant comorbid disability on the most vulnerable communities; yet interventions targeting the mental health of affected communities are lacking. A pilot study to assess the effectiveness of a chronic disease self-management program (CDSMP) was introduced to lymphatic filariasis peer support groups in Léogâne, Haiti. METHODS: Using a closed-cohort stepped-wedge cluster trial design, Hope Clubs were assigned into Arm 1 (n=118 members) and Arm 2 (n=92). Household surveys, measuring self-rated health, depression, disease self-efficacy, perceived social support, and quality of life, were conducted at baseline (before CDSMP); midpoint (after Arm 1/before Arm 2 completed CDSMP); and endpoint (after CDSMP). Non-Hope Club member patients (n=74) were evaluated at baseline for comparison. RESULTS: Fifty percent of Hope Club members (Arm 1: 48.3%, Arm 2: 52.2%) screened positive for depression at baseline, compared with 36.5% of non-Hope Club members. No statistically significant differences were found in outcome measures between intervention observation periods. At endpoint, depressive illness reduced to 28.7% (Arm 1) and 27.6% (Arm 2). CONCLUSIONS: The intervention was feasible to integrate into Hope Clubs, showed overall positive effects and reduced depressive symptoms. More studies are needed to evaluate the efficacy of implementing CDSMP in the NTD context. CONTEXTE: Les maladies tropicales négligées (MTN) infligent d'importantes incapacités comorbides aux communautés les plus vulnérables; pourtant, les interventions ciblant la santé mentale des communautés affectées font défaut. Une étude pilote visant à évaluer l'efficacité d'un programme d'autogestion des maladies chroniques (CDSMP) a été introduite dans des groupes de soutien par les pairs pour la filariose lymphatique à Léogâne, en Haïti. MÉTHODES: Dans le cadre d'un essai en grappe à cohorte fermée, les clubs Hope ont été répartis entre le bras 1 (n=118 membres) et le bras 2 (n=92). Des enquêtes auprès des ménages, mesurant l'auto-évaluation de la santé, la dépression, l'auto-efficacité face à la maladie, le soutien social perçu et la qualité de vie, ont été menées au départ (avant le CDSMP), à mi-parcours (après que le bras 1 / avant que le bras 2 ait terminé le CDSMP) et à la fin (après le CDSMP). Les patients non membres du Hope Club (n=74) ont été évalués au début de l'étude à des fins de comparaison. RÉSULTATS: Cinquante pourcent des membres du Hope Club (bras 1 : 48,3%, bras 2 : 52,2%) ont été dépistés positifs pour la dépression au début de l'étude, contre 36,5% des non-membres du Hope Club. Aucune différence statistiquement significative n'a été constatée dans les mesures des résultats entre les périodes d'observation de l'intervention. À la fin de l'étude, la maladie dépressive était réduite à 28,7% (bras 1) et 27,6% (bras 2). CONCLUSIONS: L'intervention a pu être intégrée dans les clubs Hope, elle a montré des effets globalement positifs et a permis de réduire les symptômes dépressifs. D'autres études sont nécessaires pour évaluer l'efficacité de la mise en œuvre du CDSMP dans le contexte des MTD. ANTECEDENTES: Las enfermedades tropicales desatendidas (ETDs) infligen una importante discapacidad comórbida a las comunidades más vulnerables; sin embargo, faltan intervenciones dirigidas a la salud mental de las comunidades afectadas. Se introdujo un estudio piloto para evaluar la eficacia de un programa de autogestión de enfermedades crónicas (CDSMP, por sus siglas en inglés) en grupos de apoyo entre pares de filariasis linfática en Léogâne, Haití. MÉTODOS: Utilizando un diseño de ensayo por conglomerados de cohortes cerradas escalonadas, los Clubes Esperanza fueron asignados al Grupo 1 (n=118 miembros) y al Grupo 2 (n=92). Se realizaron encuestas en los hogares para medir la autoevaluación de la salud, la depresión, la autoeficacia frente a la enfermedad, el apoyo social percibido y la calidad de vida en la línea de base (antes del CDSMP), en el punto medio (después de que el Grupo 1/antes de que el Grupo 2 completara el CDSMP) y en el punto final (después del CDSMP). Los pacientes que no pertenecían al Club Esperanza (n=74) fueron evaluados al inicio del estudio a modo de comparación. RESULTADOS: El 50% de los miembros del Club Esperanza (Grupo 1: 48,3%, Grupo 2: 52,2%) dieron positivo en depresión al inicio del estudio, en comparación con el 36,5% de los no miembros del Club Esperanza. No se encontraron diferencias estadísticamente significativas en las medidas de resultado entre los periodos de observación de la intervención. Al final, la enfermedad depresiva se redujo al 28,7% (Grupo 1) y al 27,6% (Grupo 2). CONCLUSIONES: La intervención fue factible de integrar en los Clubes Esperanza, mostróefectos positivos generales y redujo los síntomas depresivos. Se necesitan más estudios para evaluar la eficacia de la aplicación del CDSMP en el contexto de las ETD.

The potential role of artificial intelligence in the clinical management of Hansen's disease (leprosy).

Missed and delayed diagnoses of Hansen's disease (HD) are making the battle against it even more complex, increasing its transmission and significantly impacting those affected and their families. This strains public health systems and raises the risk of lifelong impairments and disabilities. Worryingly, the three countries most affected by HD witnessed a growth in new cases in 2022, jeopardizing the World Health Organization's targets to interrupt transmission. Artificial intelligence (AI) can help address these challenges by offering the potential for rapid case detection, customized treatment, and solutions for accessibility challenges-especially in regions with a shortage of trained healthcare professionals. This perspective article explores how AI can significantly impact the clinical management of HD, focusing on therapeutic strategies. AI can help classify cases, ensure multidrug therapy compliance, monitor geographical treatment coverage, and detect adverse drug reactions and antimicrobial resistance. In addition, AI can assist in the early detection of nerve damage, which aids in disability prevention and planning rehabilitation. Incorporating AI into mental health counseling is also a promising contribution to combating the stigma associated with HD. By revolutionizing therapeutic approaches, AI offers a holistic solution to reduce the burden of HD and improve patient outcomes.

Chromoblastomycosis in French Guiana: Epidemiology and Practices, 1955-2023.

Chromoblastomycosis (CBM) is a chronic neglected fungal disease, usually met in tropical areas. French Guiana is a South American territory with limited epidemiological data. This retrospective study concerned all patients with CBM proven by at least one paraclinical examination and diagnosed in French Guiana between 1950 and 2023. In total, 23 patients were included, mostly males (87%) of Creole origin, living in the coastal region (87%) and involved in outdoor occupations (74%). Lesions were mostly observed on the lower limbs (78.3%), with a median time to diagnosis of four years. Laboratory tests included positive direct microscopic examinations (78.3%) and mycological cultures (69.6%), identifying 14 cases of Fonsecaea pedrosoi and one case of Exophiala janselmei. Various treatments were employed, including antifungals, surgery and combinations of both. In conclusion, CBM in French Guiana involves a different population than other subcutaneous mycoses such as Lobomycosis or Paracoccidioidomycosis, mostly found in the forest hinterland. Surgery should be recommended for recent and limited lesions. Itraconazole and terbinafine should systematically be proposed, either in monotherapy or in combination with surgery or cryotherapy.

Prevalence of helmintic infections in Brazilian Maxakali indigenous: a repeated cross-sectional design.

BACKGROUND: The prevalence of intestinal parasites is known to be high among Amerindian populations; further, there are serious problems in the healthcare of these populations in Brazil. The Maxakali, located in the northeastern region of Minas Gerais, Brazil, is an indigenous group that still preserves many of its cultural aspects. This study aimed to compare the positivity rate of schistosomiasis and soil-transmitted helminths in this ethnic group in epidemiological surveys conducted in 1972 and 2014. METHODS: Stool parasitological examinations were performed by the Kato-Katz technique during both periods in this population. In 2014, the parasitological diagnosis was also realized with the TF-Test® technique. RESULTS: In 1972, 270 inhabitants were examined. The positivity rates were 67.4% for Schistosoma mansoni, 72.9% for hookworms, 43.7% for Ascaris lumbricoides, and 23.7% for Trichuris trichiura. In 2014, 545 individuals were examined, and the positivity rates obtained were 45.7% for S. mansoni, 22.8% for hookworms, 0.6% for A. lumbricoides, and 2.8% for T. trichiura. CONCLUSIONS: The comparison of the parasitological surveys conducted in 1972 and 2014, indicates that the indigenous Maxakali remained neglected by the health and indigenous protection authorities during these four decades. The infection rate observed in 2014 for schistosomiasis and hookworm remains high, considering the current epidemiological view of these diseases in the Brazilian population.

Musculoskeletal involvement in neglected tropical diseases: a comprehensive review.

Neglected tropical diseases (NTDs) encompass a group of diseases predominantly found in tropical regions, with origins dating back to their inclusion in the United Nations Millennium Development Goals in 2000. This initiative aimed to raise awareness and global funding to combat these diseases, which thrive in areas with limited sanitation, healthcare, and education. NTDs are caused by various pathogens such as bacteria, fungi, parasites, and viruses and affect over two billion individuals in resource-poor communities, leading to preventable deaths and devastating consequences. While the musculoskeletal system is only occasionally affected, the resulting chronic disabilities prevent individuals from working, posing a significant socioeconomic burden in this region of the world. Some NTDs exhibit distinct imaging features, and radiologists need to be aware of these characteristics to facilitate early treatment. In this review, we delve into musculoskeletal NTDs, focusing on clinical features and imaging findings, differential diagnosis, and clinical management.

Curcumin-loaded nanostructured systems for treatment of leishmaniasis: a review.

Leishmaniasis is a neglected tropical disease that has affected more than 350 million people worldwide and can manifest itself in three different forms: cutaneous, mucocutaneous, or visceral. Furthermore, the current treatment options have drawbacks which compromise efficacy and patient compliance. To face this global health concern, new alternatives for the treatment of leishmaniasis have been explored. Curcumin, a polyphenol obtained from the rhizome of turmeric, exhibits leishmanicidal activity against different species of Leishmania spp. Although its mechanism of action has not yet been fully elucidated, its leishmanicidal potential may be associated with its antioxidant and anti-inflammatory properties. However, it has limitations that compromise its clinical use. Conversely, nanotechnology has been used as a tool for solving biopharmaceutical challenges associated with drugs, such as curcumin. From a drug delivery standpoint, nanocarriers (1-1000 nm) can improve stability, increase solubility, promote intracellular delivery, and increase biological activity. Thus, this review offers a deep look into curcumin-loaded nanocarriers intended for the treatment of leishmaniasis.

Protective efficacy of the oral vaccine Tc24:Co1 produced in Schizochytrium sp. against Trypanosoma cruzi infection in a mouse model.

Trypanosoma cruzi parasite - causal Chagas disease agent - affects about 7 million people; no vaccine is available, and current medications have not been entirely effective. Multidisciplinary efforts are necessary for developing clinical vaccine prototypes. Thus, this research study aims to assess the expressed and whole-cell administration protection of the oral vaccine prototype Tc24:Co1 using Schizochytrium sp. microalga. High recombinant protein expression yields (675 µg/L) of algal culture were obtained. Additionally, Schizochytrium sp.-Tc24:Co1 resulted stable at 4 °C for up to six months and at 25 °C for three months. After receiving four oral doses of the vaccine, the mice showed a significant humoral immune response and a parasitemia reduction associated with a lack of heart inflammatory damage compared with the unvaccinated controls. The Schizochytrium sp.-Tc24:Co1 vaccine demonstrates to be promising as a prototype for further development showing protective effects against a T. cruzi challenge in a mouse model.